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Once a focal lesion is localized to a specific area of the nervous system (anatomical diagnosis), the pathology (pathological diagnosis) and etiology (etiological diagnosis) of the lesion should be determined.

How to reach a pathological diagnosis
The pathological diagnosis can only be made by direct pathological evaluation of a specimen obtained from the focal lesion. When direct evaluation of a specimen is not possible, a tentative pathological diagnosis can be made based on the clinical, neuroradiological, and neurophysiological findings.
The clinical findings that are most helpful to establish a tentative pathological diagnosis are those related to the location of the lesion and the rate of progression of the neurological deficit.
The location of a lesion helps to establish a tentative pathological diagnosis because certain pathological processes are more likely to occur in specific areas of the nervous system than in others. Neoplasms in the neonatal period occur more often in the supratentorial region than in the infratentorial region. Single artery infarcts occur more often in the middle cerebral circulation than in the posterior cerebral circulation.
The speed of progression of a deficit—the time it takes for a deficit to reach maximal neurological impairment—may help to differentiate neoplasms, acute cerebrovascular accidents, and infections. Neoplastic processes progress relentlessly during the neonatal period. Acute cerebrovascular accidents reach maximal neurological impairment in minutes or hours. Infectious processes reach maximal neurological impairment in hours or days.
The event surrounding the onset of symptoms does not contribute as much to the formulation of a tentative pathological diagnosis as the location of the lesion or the speed of progression of the deficit, except with traumatic processes. In traumatic processes the onset of symptoms is usually clearly related to the traumatic event.

How to reach an etiological diagnosis
Once a tentative pathological diagnosis is reached, the etiological diagnosis is determined by a combination of clinical, neuroimaging, and laboratory findings.