Chapter 17 Neurology

Insider’s Guide to Neurology for the USMLE Step 1

Neurology is one of the toughest subjects on boards simply because of the broad range of information that you must learn for this topic area. Unfortunately, there is no way to comprehensively cover all of the information that you must know for neurology in this chapter or any single boards review book. The best-prepared students use a mix of review sources to study for neurology. You might consider having a proper neurology textbook nearby so that you can refer to some diagrams included in it as well.

High-yield neurology topics include degenerative disorders, Alzheimer’s disease, spinal cord syndromes, and central nervous system (CNS) lesions that result from to neuronal damage (e.g., cranial nerve lesions, upper motor neuron [UMN] vs. lower motor neuron [LMN] signs) or arterial occlusions. When it comes to strokes and cranial nerve damage, simply knowing the general functional deficits that you would expect to find in the patient is not enough. Boards will expect you to predict the side of the body that will be affected based on the site of the lesion. Although this may seem like a simple task, be aware that it can be difficult to muster enough brain power to reason through this type of problem after sitting through such a long examination. Practice, practice, and practice while studying, and you will sharpen your intuition and minimize your efforts on test day.

We should mention that neuroanatomy is also high-yield for boards. You will be expected to recognize anatomic structures present at various levels of the brain or spinal cord and make clinical correlations to diseases that affect these structures. This will require you to know which section of the CNS you are looking at when presented with an image. First Aid will not adequately prepare you for this topic. We recommend using High-Yield Neuroanatomy of the High-Yield Series. Not only does this book cover the depth of information that you need to breeze through neuroanatomy on boards, but users also are quite impressed with its brevity.

Basic concepts

1 What is a motor unit? Will most α motor neurons innervate a few or many muscle fibers in a large muscle such as the gluteus maximus?

A motor unit is a group of muscle fibers that are all innervated by a single α motor neuron. In the large muscles, α motor neurons will innervate many muscle fibers, which is why fine control of muscle movement (contraction) is limited. On the other hand, in the smaller muscles (e.g., extraocular muscles or muscles of the hand), a given α motor neuron will innervate only a few muscle fibers, resulting in much finer control of movement. In both types of muscle, increasing the strength of muscle contraction occurs primarily by recruitment of additional motor units.

2 How do upper motor neurons differ from lower motor neurons?

Motor neurons, as the name implies, are neurons involved in stimulating movement. The axons of lower motor neurons (LMNs) (α and γ motor neurons) project directly to skeletal muscle fibers, while upper motor neurons (UMNs) originate in the motor region of the brainstem and cerebral cortex and have no direct contact with skeletal muscles (Fig. 17-1). The cell bodies of UMNs are supraspinal in location, and the axons of these neurons synapse either directly or indirectly, via interneurons, on LMNs located in the ventral horn of the spinal cord or brainstem motor nuclei (e.g., facial nerve motor nucleus).

Figure 17-1 Examples of somatic motor pathways.

(From Thibodeau G, Patton K: Anatomy & Physiology, 6th ed. St. Louis, Mosby, 2006.)

UMN lesions produce a different set of symptoms than LMN lesions that you should recognize for boards. While LMN lesions result in flaccid paralysis and weakened reflexes due to decreased contractions from denervated muscles, UMN lesions result in a spastic paralysis and heightened reflexes due to loss of inhibition of γ motor neurons by UMNs. LMN lesions result in fasciculations (random twitches of denervated motor units) and muscle atrophy. UMN lesions are associated with a positive Babinski sign (toes extend upward with plantar stimulation), but LMN lesions are not. UMN and LMN symptoms are explored further in Case 17-1.

3 What is the primary function of the cerebellum in movement?

The cerebellum fine-tunes movement. It does this by comparing commands sent by the motor cortex to the muscular system with proprioceptive feedback (via the spinocerebellar tracts) it receives about the movement that actually occurred. When differences in the planned movement and the actual movement occur, the cerebellum uses this feedback to correct errors and influence future output of the motor cortex.

4 Why do cerebellar lesions classically produce ipsilateral symptoms?

The cerebellar hemispheres influence motor activity by their projections to the contralateral motor cortices (via the motor thalamus) and to the contralateral red nuclei. In turn, both the corticospinal tract and the rubrospinal tract arising from these structures cross back over en route to their target motor neurons, thereby producing symptoms on the same side of the body as the lesion.

5 What are the two ascending sensory pathways and what information does each convey?

1. The anterolateral system, also referred to as the spinothalamic tract, conveys sensations of pain, temperature, and crude (nondiscriminative) touch.

2. The dorsal column–medial lemniscus pathway conveys the sensations of fine touch, vibration, pressure, and conscious proprioception.

Note: Unconscious proprioception is transmitted by the spinocerebellar pathways.

6 What are the two anatomic divisions of the dorsal columns, and from which anatomic structures do these respective divisions relay sensory information?

1. The fasciculus gracilis, which relays information from the lower extremities and from the lower thorax (level T7 and below), is located most medially in the dorsal columns, just as the gracilis muscle is the most medial muscle of the thigh.

2. The fasciculus cuneatus, which relays information from the upper thorax and the upper extremities (levels C2-T6; recall that the C1 spinal nerve provides motor innervation to the muscles of the occipital region) is immediately lateral to the fasciculus gracilis (Fig. 17-2).

Figure 17-2 A, The formation and course of the posterior columns in the spinal cord and the medial lemniscus in the brainstem. B, Divisions of the ascending sensory pathways.

(A modified from Carpenter MB: Human Neuroanatomy. Baltimore, Williams & Wilkins, 1983. B from Lindsay KW, Bone I, Callander R: Neurology and Neurosurgery Illustrated, 3rd ed. Edinburgh, Churchill Livingstone, 2002.)

Note: Both fasciculi carry fibers that synapse on their respective nuclei in the medulla, the nucleus gracilis and nucleus cuneatus.

7 At what neuroanatomic locations do projections in the corticospinal tract, dorsal columns, and anterolateral system (spinothalamic system) cross over?

The corticospinal tract crosses over (i.e., decussates) as it descends along the inferior aspect of the medulla through the medullary pyramids. The dorsal columns’ (ascending) projections cross over between their nuclei in the brainstem and the thalamus, via the internal arcuate fibers of the medial lemniscus, which are located in the caudal medulla. The axons of the anterolateral system cross over almost immediately after their first-order neurons synapse in the dorsal horn of the spinal cord.

Step 1 Secret

You must know where common tracts such as the corticospinal tract, dorsal column–medial lemniscus pathway, and spinothalamic tract decussate because this will determine the side on which a patient experiences symptoms if one of the neurons in the aforementioned pathways is damaged. Remember, the USMLE is most interested in clinically relevant information! It will be far more valuable for you to practice pinpointing the site of a patient’s lesion based on common sets of symptoms than to memorize a dozen different tracts.

8 Because you know where the major motor and sensory pathways cross over, identify and explain the neurologic deficits that occur in the Brown-Séquard syndrome

Brown-Séquard syndrome is caused by a lateral hemisection of the spinal cord. The motor loss will be on the same side as that of the lesion, because the corticospinal tract has already crossed superior to the lesion (in the medulla), and in the spinal cord it innervates only motor neurons on the same side as it courses. Loss of LMNs in the anterior horn will result in ipsilateral symptoms of hyporeflexia and flaccid paralysis at the level of the lesion. However, ipsilateral UMN signs will also be present because UMNs synapse with LMNs at all levels of the spinal cord.

The loss of fine touch, vibration, and proprioception (modalities of the dorsal columns) will be on the same side as that of the lesion. This is because the sensory information of the dorsal columns does not cross over until a more superior location (between the brainstem nuclei and the thalamus). The loss of pain and temperature sensation (anterolateral system), however, will be contralateral to the side of the lesion, because the fibers of the anterolateral system ascend and cross over shortly after entering the spinal cord (Fig. 17-3).

Figure 17-3 Brown-Séquard syndrome.

(From Lindsay KW, Bone I, Callander R [eds]: Neurology and Neurosurgery Illustrated, 3rd ed. Edinburgh, Churchill Livingstone, 2002.)

Note: There may be some loss of all modalities at the level at which the lesion occurs.

9 Where will the motor and sensory deficit manifest (below the head) if there is a lesion of the internal capsule?

The corticospinal tract, dorsal columns, and anterolateral system all travel to or from the cerebral cortex through the posterior limb of the internal capsule. Because all these tracts either originated from, or will eventually cross over to, the contralateral side, there will be a contralateral hemiplegia from effects on the corticospinal tract, along with a contralateral sensory loss from both ascending sensory systems.

Case 17-1

A 45-year-old man presents with a 6-month history of unexplained muscle weakness, dysphagia, and dysarthria. When reaching above his head to reshelve heavy board review books, he experiences arm weakness, accompanied by shoulder muscle cramps and neck cramps. His dysphagia and dysarthria manifest as difficulty swallowing both liquids and solids and a slow, strained speech pattern.

1 How might we approach a case of suspected motor neuron disease?

Consider that the lesion might occur at the level of motor neurons, neuromuscular junctions, or muscles. For example, the differential diagnosis for muscle weakness, dysarthria, and dysphagia may include amyotrophic lateral sclerosis (a disease of motor neurons), myasthenia gravis (an autoimmune attack at the neuromuscular junction), or polymyositis (an inflammatory disease of muscle). Suspected motor neuron disease can then be investigated for UMN or LMN signs.

Case 17-1 continued:

Physical examination of upper and lower extremities reveals a strange combination of flaccid and spastic paralysis, as well as hypo- and hyperreflexia. Diffuse muscle wasting and fasciculations are visible on the lateral aspects of the tongue. Sensation is intact to all modalities in all areas tested. A mini-mental status examination is within normal limits for the patient’s age and cultural background, though he does have difficulty articulating.

2 What upper motor neuron signs are present in this patient?

UMN lesion signs include spastic paralysis (the muscles have an increased resistance to passive movement or manipulation), hyperreflexia (hyperactivity of deep tendon reflexes [DTRs]), and clonus (alternating contraction and relaxation of a muscle in rapid succession in response to sudden stretching of the muscle). Notice this patient has spastic paralysis and hyperreflexia.

3 Why are the signs of hyperreflexia, spastic paralysis, and clonus seen with an upper motor neuron lesion?

The most widely accepted theory is that UMNs are tonically inhibitory to LMNs, such that disruption of UMNs will disinhibit (i.e., allow activation of) LMNs. This makes the motor component of the DTRs more active and increases baseline muscle tone, which increases resistance to passive movement.

4 What lower motor neuron signs are present in this patient?

When an LMN is damaged, the muscle it innervates does not get stimulated, so the muscle atrophies and has less tone (hypotonia). The denervated muscle also has flaccid paralysis (the muscles have decreased resistance to passive movement or manipulation), and the efferent part of the DTRs is blunted, so the DTRs are weak or absent (hyporeflexia).

Note: LMN involvement can be evaluated by electromyography (EMG) and nerve conduction studies.

Case 17-1 continued:

Serum analysis is negative for antibodies to the acetylcholine (ACh) receptor. Cerebrospinal fluid (CSF) analysis is negative for oligoclonal bands (of immunoglobulins), elevated protein, or white blood cells (WBCs). Magnetic resonance imaging (MRI) of the brain and spinal cord appears normal. A muscle biopsy is shown in Figure 17-4.

Figure 17-4 Muscle biopsy from a patient with spinal muscular atrophy type I demonstrating denervation atrophy with residual hypertrophic fibers (magnification × 300).

(From Samuels MA, Feske SK: Office Practice of Neurology, 2nd ed. Philadelphia, Churchill Livingstone, 2003.)

5 What process leads to the findings seen in this biopsy specimen stained with hematoxylin-eosin (H&E)?

The atrophied and angulated fibers reflect denervation due to the death of the innervating motor neurons. This death of an entire group of neighboring muscle fibers (of the same type, because they are innervated by the same motor neuron) is called group atrophy. It occurs with disease progression.

6 What would myosin adenosine triphosphatase (ATPase) staining of this specimen show?

This histologic stain would distinguish type I (slow twitch) from type II (fast twitch) muscle fibers. Normally, these different types of muscle fibers will be intermingled in a checkerboard-like pattern, owing to the innervation of adjacent muscle fibers by different anterior horn motor neurons. However, when muscle fibers lose their motor innervation due to death of anterior horn cells, the axons that innervate neighboring muscle fibers will sprout new axons and take over the denervated fibers. This leads to type grouping, in which muscle fibers of the same type are grouped together, with loss of the checkerboard pattern.

7 What is the most likely diagnosis?

Amyotrophic lateral sclerosis (ALS), or Lou Gehrig disease, is a chronic neurodegenerative disease of both UMNs and LMNs that results in muscle weakness, disability, and death typically within 3 to 5 years. Causes of death typically include respiratory failure, aspiration pneumonia resulting from respiratory muscle weakness, skin ulcers causing systemic infection, and deep vein thrombosis causing pulmonary thromboembolism.

Note: Myotrophic means “muscle enlargement.” Amyotrophia means “muscle atrophy.” Lateral sclerosis refers to palpable hardness of the lateral columns of the spinal cord at autopsy, due to sclerosis of the lateral corticospinal tracts.

8 Why are the magnetic resonance imaging and cerebrospinal fluid findings notable?

The absence of periventricular plaques on MRI and oligoclonal bands in CSF makes the diagnosis of multiple sclerosis (MS) much less likely, as most MS patients have these findings. Another important distinction between MS and ALS is that ALS affects only the motor system, whereas MS affects both motor and sensory systems. The distinction between these diseases is important: Although both are incurable, ALS is relentlessly progressive, whereas MS has a more variable natural history.

9 What are the principal pathologic findings in amyotrophic lateral sclerosis?

There is loss of pyramidal cells in the motor cortex, leading to fibrosis (which generally manifests in the central nervous system [CNS] as astrocytic gliosis) of the lateral corticospinal tracts. In addition, there is loss of ventral horn neurons throughout the length of the spinal cord, resulting in thinning of ventral (motor) nerve roots. The affected muscles show denervation atrophy with (muscle) fiber type grouping upon reinnervation. There usually is sparing of sensory tracts and cognitive function, which explains why this patient’s mental status and sensory function are both completely normal. Extraocular muscles also are often spared, leaving some patients with severe disease progression no means of communication other than eye movements (Fig. 17-5).

Figure 17-5 Sites of the lesions in amyotrophic lateral sclerosis (ALS).

(From Pryse-Phillips WM, Murray TJ: Essential Neurology: A Concise Textbook. New York, Medical Examination Publishing, 1992.)

Note: Diffuse muscle atrophy with UMN lesions might occur secondary to muscle disuse but does not occur as a result of UMN loss. The group atrophy seen in ALS is secondary to muscle denervation due to LMN loss.

10 What might you expect electromyography and nerve conduction studies to show in this patient?

EMG could indicate LMN involvement by revealing signs of denervation (fibrillation potentials). Fibrillations are invisible contractions of single muscle fibers, seen on EMG only. Fasciculations are involuntary contractions of one or more muscle units (which are often visible) and may also be present in LMN lesions. Notice this patient had fasciculations, often visible in the tongue. Nerve conduction studies are typically normal (or close to normal).

11 Is amyotrophic lateral sclerosis more commonly inherited or acquired?

ALS is more commonly acquired than inherited. The precise etiology of the acquired form remains unknown. However, one of the familial forms has been associated with mutations in the zinc/copper superoxide dismutase 1 gene, which plays an important role in scavenging free radicals in metabolically active cells such as neurons.

12 Why is amyotrophic lateral sclerosis often confused for syringomyelia and vice versa?

Syringomyelia is a disease marked by enlargement of the central canal of the cervical spinal cord. This leads to destruction of the anterior horn cells in the upper levels of the spinal cord, resulting in atrophy of intrinsic hand muscles. Because atrophy and weakness of hand muscles are early signs of both ALS and syringomyelia, the disease presentations are often confused. However, enlargement of the central canal in syringomyelia also affects the decussating fibers of the anterolateral spinothalamic tract, resulting in bilateral loss of pain and temperature sensation in the upper extremities. ALS, on the other hand, has no sensory changes!

Summary Box: Amyotrophic Lateral Sclerosis

Clinical presentation is one of chronic degeneration of upper and lower motor neurons, generally without sensory or cognitive involvement.

Pathologic examination shows degeneration of pyramidal cells in the motor cortex and fibrosis of the lateral corticospinal tract. These areas are replaced with reactive astrogliosis.

Muscle biopsy shows type grouping and group atrophy of muscle fibers.

Most cases are acquired; one familial form is associated with superoxide dismutase 1 mutations.

Amyotrophic lateral sclerosis (ALS) and syringomyelia both result in hand muscle atrophy. Syringomyelia also results in bilateral loss of pain and temperature sensation, while ALS is not associated with sensory changes.

Resting tremor occurs when the patient is not moving (resting) and typically decreases with voluntary activity. Intention tremor, which typically has cerebellar origins, appears as the patient moves a limb toward a target, and is often irregular in amplitude and trajectory. Postural tremor, the most common cause of which is essential tremor, appears as the patient actively holds the limbs in a position against gravity.

Case 17-2 continued:

During the interview, you note that the tremor appears at rest and disappears when the patient either extends his arms parallel to the floor or reaches for a pen. However, he has difficulty initiating movement to reach for a pen (akinesia), finally doing so successfully, albeit slowly (bradykinesia). You also note an expressionless face, decreased spontaneous blink rate, and forward stooped posture. On physical examination, the patient maintains this posture and walks with a slow, narrow-based, festinating gait. Motor examination shows that his muscles demonstrate a cogwheel rigidity, in which muscle rigidity gives way to passive stretching in series of successive jerks.

3 In light of these signs, what is the most likely diagnosis for the tremor?

This is a classic presentation for Parkinson’s disease, which is the most common cause of resting tremor. Parkinson’s disease frequently presents with a triad of resting tremor, bradykinesia, and cogwheel rigidity. This patient has the triad, as well as characteristic masked facies, stooped posture, and festinating gait.

4 How does a festinating gait differ from an ataxic gait?

A festinating gain is due to lesions of the substantia nigra pars compacta, a member of the basal ganglia, and manifests as an unsteady, shuffling gait consisting of narrow-based steps. When directed to turn around, patients often do so “en bloc,” by taking many small steps without twisting the torso. An ataxic gait is due to lesions of midline cerebellar structures and manifests as unsteady wide-based steps, with staggering side to side. A subtly ataxic gait can be detected with heel-to-toe gait testing.

5 Why should we determine whether this patient is taking medications such as haloperidol or metoclopramide?

The pathophysiology of Parkinson’s disease is related to insufficient dopaminergic activity within the brain, because the substantia nigra pars compacta serves as the site of dopamine production. Certain antipsychotic and antiemetic agents that act as central dopamine receptor antagonists may cause or exacerbate parkinsonian symptoms such as rigidity, bradykinesia, and resting tremor. When making the diagnosis, it is critical for physicians to distinguish Parkinson’s disease from parkinsonism, which can present with a similar symptomatology and may be drug-induced, postencephalitic, or neurodegenerative but with different anatomic lesions from those in Parkinson’s disease.

6 What cerebral structures are affected in Parkinson’s disease, and how does this play into the bradykinesia and akinesia observed?

In Parkinson’s disease, the dopaminergic, neuromelanin-containing neurons in the substantia nigra selectively degenerate over time. These neurons normally project to the basal ganglia via the nigrostriatal tract. The basal ganglia then influence execution of learned motor plans by modulating signals between the thalamus and motor cortex. Within the basal ganglia, there are two pathways leading to output to the thalamus: the direct and indirect pathways. Activation of the direct pathway facilitates desired movement by stimulating the thalamus via inhibition of the globus pallidus internus and substantia nigra pars reticularis (both of which normally inhibit the thalamus), whereas activation of the indirect pathway inhibits unwanted movement by inhibiting the thalamus. Nigrostriatal dopaminergic inputs activate the direct pathway and inhibit the indirect pathway, thus stimulating motion. Decreased dopamine levels in Parkinson’s disease manifest with a net decrease in motor activity. However, this model does not yet account for the patient’s tremor. Because dopamine decreases release of ACh, a decrease in dopamine levels leads to a relative excess of striatal ACh in patients with Parkinson’s disease. ACh opposes the actions of dopamine and activates the indirect pathway, which disinhibits suppression of unwanted movements and results in the pill-rolling tremor that is characteristic of the disease. It is important that you understand the imbalance of dopamine and ACh levels in Parkinson’s patients because dopamine agonists and anticholinergics are useful in treating this disease (Fig. 17-6).

Figure 17-6 Schema of anatomic nuclei and pathways involving the basal ganglia. Black arrows represent excitation, and speckled arrows represent inhibition. GP_e, globus pallidus, external segment; GP_i, globus pallidus, internal segment; SNc, pars compacta of the substantia nigra; SNr, pars reticularis of the substantia nigra; STN, subthalamic nucleus; thal, thalamus.

(From Goetz CG: Textbook of Clinical Neurology, 2nd ed. Philadelphia, WB Saunders, 2003.)

Note: The striatum consists of the caudate nucleus and putamen, both of which are part of the basal ganglia. You should be able to identify the basal ganglia on an anatomic section. The caudate and thalamus lie medial to the internal capsule, and the globus pallidus and putamen lie lateral.

Case 17-2 continued:

When you see the patient in clinic 6 months later, you note marked improvement of his bradykinesia and resting tremor. You attribute this success to the patient’s current treatment course.

7 What medication did you start the patient on, and why is it, rather than dopamine, used to treat Parkinson’s disease?

Dopamine cannot cross the blood-brain barrier. However, levodopa (L-dopa), a lipid-soluble precursor to dopamine, can cross the blood-brain barrier and increases CNS dopamine levels once converted by dopa decarboxylase. In fact, parkinsonian syndromes are often initially misdiagnosed as Parkinson’s disease, and the diagnosis later corrected when the patient does not respond to L-dopa.

8 Why is levodopa typically administered along with carbidopa?

Carbidopa is a dopa decarboxylase inhibitor that cannot cross the blood-brain barrier, so it inhibits the peripheral metabolism of L-dopa to dopamine. This both increases the delivery of L-dopa to the brain and minimizes the side effects of peripheral L-dopa/dopamine. These side effects include autonomic symptoms such as orthostatic hypotension, nausea/vomiting, confusion, hallucinations, and infrequently, arrhythmias. Long-term side effects include dyskinesia, particularly choreoathetosis of the face and distal extremities. CNS symptoms (confusion and hallucinations) are last to disappear.

9 Drugs such as bromocriptine and pergolide are also used to treat Parkinson’s disease. How do they exert their effects?

These drugs are dopamine receptor agonists and increase central dopaminergic activity without increasing dopamine levels, which of course is beneficial in Parkinson’s disease.

10 What is the mechanism of action of selegiline, a drug used in treating Parkinson’s disease?

Selegiline selectively inhibits monoamine oxidase B (MAO-B), an enzyme that degrades dopamine. Selegiline can cross the blood-brain barrier, so it can be used without L-dopa.

11 Why is it preferable to selectively inhibit monoamine oxidase B, rather than both monoamine oxidase A and monoamine oxidase B, in Parkinson’s disease?

Monoamine oxidase A (MAO-A) principally degrades norepinephrine and serotonin, whereas MAO-B is more selective for dopamine degradation. Because MAO-A inhibitors increase serotonin and norepinephrine levels, they have been used for treating depression, but they are not expected to be as effective in treating the motor symptoms of Parkinson’s disease.

12 What is benztropine and why is it useful in Parkinson’s disease?

Benztropine is an anticholinergic drug (like atropine) that crosses the blood-brain barrier. Recall that there is a relative excess of striatal ACh in Parkinson’s disease because of the deficiency of dopamine. Thus, anticholinergics that can enter the CNS are also useful in treating the bradykinesia and akinesia of Parkinson’s disease.

13 Which antiviral medication is also effective in treating Parkinson’s disease?

Amantadine, which is effective against influenza A, was incidentally discovered to be effective in Parkinson’s disease. Though its mechanism is not fully understood, amantadine has anticholinergic and antiglutamatergic effects and also acts by increasing dopamine output from intact nerve terminals.

14 How does the drug MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) cause parkinsonism, and is this a reversible process?

MPTP is an analog of the opioid meperidine and is occasionally present as a contaminant in certain illicit drugs. It causes irreversible parkinsonism by selectively destroying neurons in the substantia nigra. In fact, the clinical and pathologic consequences of MPTP toxicity mimic those of Parkinson’s disease so well that MPTP is often used in animal models to study Parkinson’s disease.

15 Why should you be suspicious of a diagnosis of Parkinson’s disease in a patient being treated for schizophrenia?

Antipsychotic drugs that block dopamine receptors in the mesolimbic system to achieve their effect can also block dopaminergic activity in the nigrostriatal tract and cause symptoms similar to those of Parkinson’s disease (pseudoparkinsonism, which is often reversible with discontinuation of the antipsychotics). However, the choreoathetoid motor disorders that develop after prolonged use of antipsychotics (e.g., tardive dyskinesia) may prove to be irreversible.

16 What would a pathologist look for to establish the diagnosis of Parkinson’s disease in evaluation of the brain at autopsy?

Bilateral depigmentation of the midbrain substantia nigra, due to loss of dopaminergic, neuromelanin-containing neurons (Fig. 17-7A [normal] and B [Parkinson’s])

The presence of neuronal Lewy bodies in degenerated substantia nigra neurons (eosinophilic, cytoplasmic inclusions containing α-synuclein and ubiquitin) (Fig. 17-7C)

Figure 17-7 Parkinson’s disease (PD). A, Normal substantia nigra. B, Depigmented substantia nigra in idiopathic PD. C, Lewy bodies in a substantia nigra neuron stain bright pink.

(From Kumar V, Abbas AK, Fausto N: Robbins and Cotran Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2005.) (C courtesy of Dr. R. Kim, VA Medical Center, Long Beach, CA.)

Summary Box: Parkinson’s Disease