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

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

  
  
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  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:

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).

The time course of symptom onset and evolution may be described as sudden/hyperacute (over seconds to minutes), acute (over hours to days), subacute (over days to weeks to months), or chronic (over months to years) (Fig. 1–1). As a general “first pass” in neurologic differential diagnosis based on the timing of symptom onset and pace of symptom evolution (with a few exceptions noted below):

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  Hyperacute (over seconds to minutes):

  
  
  
  
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    Vascular (e.g., ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage)

    
    
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    Seizure

    
    
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    Migraine

    
    
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    Metabolic (e.g., hyperglycemia or hypoglycemia)

    
    
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    Drugs/Toxins

    
    
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    Trauma

  
  
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  Acute to subacute (over hours to days):

  
  
  
  
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    Infectious (bacterial and viral infections of the nervous system; e.g., meningitis, encephalitis, abscess)

    
    
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    Inflammatory/demyelinating (e.g., Guillain-Barré syndrome, flare of multiple sclerosis)

    
    
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    Metabolic (e.g., uremia, hepatic encephalopathy, hyponatremia or hypernatremia)

    
    
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    Drugs/Toxins

  
  
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  Subacute to chronic (over days to weeks to months)

  
  
  
  
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    Neoplastic

    
    
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    Inflammatory/demyelinating (e.g., chronic inflammatory demyelinating polyradiculoneuropathy [CIDP]), paraneoplastic syndromes)

    
    
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    Infectious (fungal, tuberculous, and parasitic infections, neurologic complications of AIDS)

    
    
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    Metabolic (e.g., vitamin B12 deficiency)

    
    
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    Drugs/Toxins

  
  
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  Chronic (over years)

  
  
  
  
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    Neurodegenerative diseases (e.g., Alzheimer’s disease, Parkinson’s disease)

Note that if one keeps in mind that metabolic abnormalities, drugs, and toxins can cause neurologic dysfunction over nearly any time course (depending on the metabolic abnormality, drug, or toxin), the rest of this schema distills to:

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  Hyperacute: vascular, seizure, migraine, trauma

  
  
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  Acute to subacute: infectious, inflammatory/demyelinating

  
  
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  Subacute to chronic: neoplastic, inflammatory/demyelinating, infectious

  
  
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  Chronic: neurodegenerative

There are a few important exceptions to this general schema:

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  Chronic diseases may present acutely. For example, although focal deficits from tumors usually emerge and evolve subacutely, a brain tumor may be asymptomatic until it causes an acute seizure. Another example of a chronic disease that can present acutely is relapsing remitting multiple sclerosis, a chronic disease characterized by acute exacerbations.

  
  
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  Although most vascular problems present hyperacutely, chronic subdural hematoma is an example of a vascular condition that presents subacutely/chronically (see Ch. 19).

  
  
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  Fungal infections, tuberculosis, and neurologic complications of AIDS may present subacutely compared to bacterial and viral infections, which present more acutely (see Ch. 20).

With the exception of seizure and migraine, which are exclusively cerebral phenomena, the other categories apply across most levels of the neuraxis. For example, sudden-onset findings localizing to a particular part of the brain suggest a vascular cause, and this is also true of the spinal cord (e.g., spinal infarct, spinal epidural hemorrhage) and even of a sudden-onset peripheral nerve palsy (e.g., nerve infarction as can be seen in vasculitis). Acute inflammatory disease of the brain (e.g., acute flare of multiple sclerosis), spine (e.g., transverse myelitis), or peripheral nerves (e.g., Guillain-Barré syndrome) all emerge and evolve over hours to days.

In addition to the time course of symptom onset and evolution, the history must elicit associated concurrent or preceding symptoms to contextualize the patient’s primary symptom. For example, if the presenting symptom is weakness, is this weakness accompanied by sensory changes and/or pain? Is the presenting symptom restricted to the limb most prominently noted by the patient or is it also present elsewhere? If the complaint is headache, is there associated nausea/vomiting or are there visual changes? Such questions establish the full range of the patient’s symptoms beyond the “chief complaint” most salient to the patient, aiding in localization of the cause of the patient’s symptoms.

Of course, as in all areas of medicine, each symptom must also be fully characterized by the clinical history with respect to its quality, severity, exacerbating and alleviating factors, and any accompanying symptoms within the context of past medical history, family history, social history, and medications.

The clinical history should allow for an initial hypothesis to be generated about where in the nervous system the problem may be as well as what it may be, and the neurologic examination provides further information to support or refute this hypothesis.

The neurologic examination is a critical tool in localization, confirming or refuting hypotheses generated during the history, or sometimes giving rise to new ones entirely. For example, is the patient’s presenting problem of “difficulty moving one hand” due to weakness, slowed movement, numbness, pain, incoordination, or inability to execute a complex movement plan? Each of these possibilities can be tested in the course of the neurologic examination.

With each element of the neurologic examination, it is important to consider which systems and structures within the nervous system are being evaluated and how their dysfunction could manifest. When working toward mastery of the neurologic examination and its interpretation, it is helpful to try to imagine the pathways involved while examining them. For example, when testing the pupillary light reflex, think: “afferent via optic nerve to pretectal nuclei of the midbrain, efferent via Edinger-Westphal nuclei to the oculomotor nerves” (see Ch. 10). When testing a muscle, think about the name of the muscle and its nerve and nerve root supply (see Chs. 16,17).

The neurologic examination is divided into seven components:

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   Mental status

   
   
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   Cranial nerves

   
   
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   Motor

   
   
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   Sensory

   
   
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   Reflexes

   
   
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   Coordination

   
   
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   Gait

Each of these components of the neurologic examination has countless individual examination maneuvers, and only the basic elements are briefly introduced here. Many more detailed aspects of the examination of each system are described in Chapters 3,4,5,6,7,8,9,10,11,12,13,14,15,16,17 alongside a more in-depth discussion of the neuroanatomic localization and clinical significance of abnormal examination findings.