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Differential diagnosis in neurology is based on two main components determined from the clinical history and physical examination:

  • The localization of the neuroanatomic origin(s) of the patient’s symptoms and signs

  • The time course over which these symptoms and signs have arisen and evolved

These give rise to what I call the “fundamental equation” of differential diagnosis in neurology:

Differential Diagnosis = Localization × Time course

Localization relies on the clinical history and neurologic examination to determine where in the nervous system the problem is. To some extent, knowing where the problem is already begins to circumscribe what the problem is, since each level of the nervous system has a particular differential diagnosis for the types of disease processes that can affect it. The time course over which neurologic symptoms arise and evolve provides crucial information in determining what the problem is, since different disease processes emerge and develop over different time frames.


Localization is the process of determining where in the nervous system the patient’s disease process is occuring: Is the problem in the central nervous system (CNS), the peripheral nervous system (PNS), or both? Within the CNS, is there a lesion in the brain, brainstem, cerebellum, or spinal cord? More precisely, where is the lesion within those structures? For example, which level of the brainstem or spinal cord? Which hemisphere(s), lobe(s), and gyrus/gyri of the brain? Within the peripheral nervous system (PNS), is the lesion at the level of one or more spinal roots, dorsal root ganglia, peripheral nerves, muscles, or at the neuromuscular junction? If there is a root, nerve, or muscle problem, which root(s), nerve(s), and/or muscle(s) is/are involved?

Nervous system diseases may affect particular structures (e.g., the basal ganglia, the cerebellum, the peripheral nerves), a particular tissue type (e.g., white matter vs gray matter of the brain; myelin of peripheral nerves vs their axons), or one or more particular systems (e.g., the motor system, the memory system).

Localization requires a detailed understanding of neuroanatomy. Part 1 of this book presents clinical neuroanatomy alongside the clinical approach to symptoms and signs related to the anatomy under discussion. Diseases that are mentioned in Part 1 of this book are discussed in more detail with respect to their clinical features, diagnosis, and treatment in Part 2.

Localization begins with the clinical history, which should elucidate the nature of the patient’s presenting symptom(s) and allow for an initial idea of potential localization(s). For example, is a chief complaint of “difficulty walking” due to weakness, impaired coordination, altered sensation, or changes in vision? The neurologic examination provides further clues as to the neuroanatomic localization of the patient’s symptoms (see “Introduction to the Neurologic Examination” below).


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