Mechanisms of Neurologic Disease

By admin On Jun 9, 2023

Ovid: Field Guide to the Neurologic Examination

Authors: Lewis, Steven L.

Title: Field Guide to the Neurologic Examination, 1st Edition

> Table of Contents > Section 1
– Neurologic Diagnosis: General Considerations > Chapter 3 –
Mechanisms of Neurologic Disease

Chapter 3

Mechanisms of Neurologic Disease

PURPOSE

The purpose of determining the mechanism of neurologic
disease is to come closer to a patient’s diagnosis by determining the
cause of the patient’s neurologic dysfunction. By determining how the
dysfunction is occurring, the second part of the neurologic diagnostic
process is complete (after localization; see Chapter 2, Localization of Neurologic Disease), giving a more complete picture of the neurologic diagnosis.

WHEN TO DETERMINE THE MECHANISM OF NEUROLOGIC DISEASE

An attempt to determine the mechanism of neurologic
disease needs to be made in every patient who presents with a symptom
due to nervous system dysfunction. Determination of mechanism is a
thought process that should occur during and after every neurologic
history, and during and after every neurologic examination.

NEUROANATOMY OF DISEASE MECHANISM

Determination of mechanism is based less directly on neuroanatomy than is localization (see Chapter 2,
Localization of Neurologic Disease). Mechanism is intertwined in
localization (and, therefore, neuroanatomy), however, because your
choice of mechanisms is limited to those processes that are likely to
affect that region of the nervous system.

EQUIPMENT NEEDED TO DETERMINE THE MECHANISM OF NEUROLOGIC DISEASE

None (other than the equipment used for the neurologic examination—the determination of mechanism is a thought process).

HOW TO DETERMINE THE MECHANISM OF NEUROLOGIC DISEASE

In neurologic diagnosis, it is most helpful to think in
terms of general mechanisms of neurologic dysfunction and to try to
decide which of these mechanisms is likely to be causative before
proceeding with further diagnostic studies. Table 3-1
lists the major categories of neurologic disease mechanism. These
mechanisms are generic and broad; for example, the compressive
mechanism would include diverse disease processes, such as a tumor
compressing or infiltrating brain tissue, a thoracic disc compressing
the spinal cord, or a subdural hematoma causing mass effect on the
brain. The same pathologic process can even produce clinical symptoms
through several different mechanisms; for example, an intracerebral
aneurysm may produce disease when it bleeds or when it compresses
important structures (e.g., a posterior communicating artery aneurysm
causing a compressive oculomotor nerve palsy).

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TABLE 3-1 General Mechanisms of Neurologic Disease^a

Mechanism	Comments
Compressive	Includes any processes that produce dysfunction by compression of nervous system structures [e.g., tumors (benign or malignant), intervertebral discs compressing nerve roots or spinal cord, aneurysm compressing a cranial nerve]
Degenerative	Includes any process that causes progressive dysfunction due to nervous system degeneration; this mechanism is especially causative in many dementing illnesses (e.g., Alzheimer’s disease and other degenerative dementias), many movement disorders (e.g., Parkinson’s disease, Huntington’s disease), and some neuromuscular diseases (e.g., amyotrophic lateral sclerosis)
Demyelinative	May involve central nervous system myelin (e.g., multiple sclerosis) or peripheral nervous system myelin (e.g., demyelinative peripheral neuropathies, such as Guillain-Barré syndrome); demyelinative disorders often have accompanying inflammation—think of demyelinative as a subset of inflammatory etiologies
Epileptic	Produces dysfunction by abnormal electrical activity of cerebral hemispheric cortex
Hemorrhagic	Produces dysfunction by bleeding into the brain or other tissues (e.g., intraparenchymal brain hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage)
Infectious	Dysfunction occurring due to a microorganism (e.g., bacterial, viral, parasitic) invading nervous system structures; probably best thought of as a subset of inflammatory etiologies
Inflammatory	Dysfunction occurring as a result of any inflammatory process involving the central or peripheral nervous system (e.g., autoimmune, granulomatous)
Ischemic	Dysfunction due to insufficient blood supply in the central nervous system (e.g., brain, brainstem, cerebellar, or spinal cord ischemia or infarction) or the peripheral nervous system (e.g., infarction of a peripheral nerve)
Migrainous	Mechanism of brain dysfunction that is thought to be due to spreading waves of depression of cortical activity; can lead to migrainous visual, motor, sensory, or aphasic symptoms, even in the absence of headache
Metabolic (including toxic)	Mechanism of diffuse brain or brainstem dysfunction due to effect of endogenous metabolic abnormalities (e.g., hyponatremia, hepatic or uremic dysfunction) or exogenous toxins (e.g., medications)
Traumatic	Central or peripheral nervous system dysfunction due to any kind of traumatic disruption of these structures
^a In addition to the mechanisms in this list, some congenital processes may produce dysfunction due to the absence, malformation, or other developmental abnormality of nervous system structure or function since birth (whether on a microscopic or macroscopic level); this mechanism is most common with pediatric neurologic diagnoses.

The most important clues to the disease mechanism derive
from the time course of symptom development discovered from the
neurologic history. Neurologic symptoms can be transient—usually
meaning lasting from seconds to hours—or persistent. Persistent
symptoms can begin suddenly (and continue at the same severity or
ultimately improve), progress gradually from onset, or wax and wane.
Although the temporal pattern of symptom development is not specific
for a single mechanism, these temporal patterns of symptom

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development can be quite helpful in including or excluding some of these mechanisms. Table 3-2
lists some of the mechanisms suggested by different temporal courses of
neurologic symptoms, coupled with the additional information—obtained
by history and examination—about whether the dysfunction is focal or
diffuse.

TABLE 3-2 Historical Clues to Disease Mechanism Suggested by the Temporal Pattern of Symptom Development^a

Temporal Course	Distribution	Most Likely Mechanisms
Transient (lasting seconds to hours)	Focal	Focal cerebral ischemia Migraine Focal seizure
	Diffuse	Global cerebral ischemia Generalized seizure Toxic/metabolic
Sudden onset (may have gradual improvement over variable period after onset)	Focal or diffuse	Ischemia (especially embolic) Hemorrhage
Gradually progressive (usually over hours, days, or longer; may also wax and wane)	Focal	Compressive Demyelinative Ischemic (especially thrombotic) Infectious Inflammatory
	Diffuse	Degenerative^b Infectious Inflammatory Toxic/metabolic
^a Many of the processes listed here would be expected to recur in a patient (e.g., seizures, migraine, demyelination in multiple sclerosis); this table refers to the time course of individual symptom development, not necessarily the overall course of a disease process. ^b Most degenerative processes are progressive over months to years.

NORMAL FINDINGS

Patients without neurologic disease have no mechanism of disease to determine.

ABNORMAL FINDINGS

The mechanism of disease that you uncover is the
abnormal finding. During the diagnostic process, the mechanism can be
reported broadly (e.g., ischemia) or narrowly (e.g., ischemia due to a
high-grade carotid artery stenosis), as is most appropriate given the
clues from the history and examination and the outcome of
investigations.

The mechanism of disease is the adjective that goes in
front of the localization. For example, a patient with a myelopathy
(spinal cord dysfunction) as the localization of neurologic pathology
can have a compressive myelopathy (e.g., from disc or tumor), an
ischemic myelopathy (e.g., an anterior spinal artery infarct), or an
inflammatory or demyelinative myelopathy (e.g., transverse myelitis).
In the last example, sometimes a suffix is added to the region of
localization to imply a mechanism. Specifically, the suffix -itis
can be added when appropriate to invoke an inflammatory process as the
cause of dysfunction at a particular localization [e.g., an
inflammatory myelopathy is a myelitis, an inflammatory myopathy (muscle disease) can be reported as a myositis, and an inflammatory brain process can be called an encephalitis].

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ADDITIONAL POINTS

The determination of disease mechanism is highly dependent on the clues obtained from the history.
Understanding the mechanism of
dysfunction is the key to the treatment of disease or to the prevention
of further disease. For example, the treatment of brain dysfunction due
to compression is significantly different than the treatment of brain
dysfunction due to ischemia. In addition, the prevention of further
brain ischemia differs if the ischemia is due to cardiogenic embolism
or carotid artery stenosis.
Before attempting to determine the
mechanism of dysfunction, make sure you have tried to localize that
dysfunction. You can’t determine the mechanism of dysfunction if you
don’t have some idea of where the problem is.