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Page 1 of3TRANSCRIBED BY: Virra Teresa Rosales Denise PalinesCOPYREAD BY: DDHV

As always, start with anatomy:

The CorticoSpinal Tract (CST, also known as Pyramidal Tract)

starts at the motor cortex at Brodmann area 4 (althoughmotor neurons are scattered practically all over the brain).

Betz cells, which are the largest motor neurons, are situated

in area 4. These axons basically make up the tract itself.

They go down to the corona radiata, the internal capsule, the

cerebral peduncles of the midbrain, and the pons, where they

are mostly found at the base. (Some of the axons synapse

with the cranial nerve nuclei in the pons as the corticobulbar

tract.)

At the lower 1/3 of the medulla, most of the fibres decussate

to the opposite side. (A few fibres do not cross over, and

these are mainly the ones that supply the upper limbs.) They

then go down as the anterior and lateral CSTs down the

spinal cord. Their exit depends upon the muscles they supply

(whether at the upper or lower body); they synapse with the

anterior horn cells (AHC). They continue on as the roots, the

plexus, the peripheral nerve, and then to the muscle.

Upper motor neurons are those that synapse before the

AHC. The AHCs and the direct nerve supply to the muscles are

the lower motor neurons.

Pattern of Weakness

UPPER MOTOR NEURON/

SUPRANUCLEAR PARALYSIS

LOWER MOTOR NEURON/

INFRANUCLEAR PARALYSIS

Increased tone (spastic) Reduced tone (flaccid)No atrophy (or slight due to

disuse)

Weak muscles; pronounced

atrophy

No fasciculations Fasciculations

Hyperreflexia Hyporeflexia

(+) Babinski/Hoffmans No Babinski/Hoffmans

*Rigidity does not involve either. This is an extrapyramidal

sign!

Motor System Disease

Progressive degenerative disorder of motor neurons in

the spinal cord, brainstem and motor cortex.

Manifest clinically by (triad of) muscular weakness

,

atrophy and corticospinal tract signsProgresses to death in 2 to 5 years or a little longer in

exceptional cases. Seldom do patients live past 10 years.

May involve just the UMNs or just the LMNs; but more

commonly, they manifest as a combination of both (i.e.,

ALS)

These diseases are not limited to just weakness. If there

is a problem with voiding, loss of sphincter tone, or

defecating, this is most likely NOT motor system disease,

but rather a specific weakness at these areas.

If a patient complains of motor weakness with

accompanying sensory weakness

, this is also likely NOT

motor system disease.

Motor Neuron Disease Subtypes

*These present clinically different, but the pathologies are

the same.

1. Amyotrophic Lateral Sclerosis (ALS): with UMN and LMNmanifestations

2. Progressive Muscular Atrophy: PURE LMN degeneration3. Progressive Bulbar Palsy: PURE BULBAR involvement (i.e.

begin with problems of speech and swallowing)

4. Primary Lateral Sclerosis: PURE UMN degenerationAMYOTROPHIC LATERAL SCLEROSIS (ALS)

Worldwide incidence 0.4-3 per 100,000 populationMen affected nearly twice as often than women

The most common form of motor neuron disease

Approximately 10% of ALS cases are familial and

inherited as autosomal dominant. The other 90% are

sporadic cases (meaning they just develop weakness

without history).

Typical Presentation:

Weakness in distal part of one limb (e.g., mild foot drop

or wrist drop)

Weakness and wasting of intrinsic hand muscles (e.g.

Interosseous muscles disappear; as if dorsum of handshave gutters)

Frequent cramps and fasciculations (source of anxiety)

Not all fasciculations are pathologic! Some arebenign and may be caused by stress or fatigue only,

e.g. parts of your face twitching when youre tired

Fasciculations are pathologic only if they areassociated with weakness and reduced muscle bulk

As the disease worsens, atrophy and weakness of the

hands, arms, shoulders and leg muscles, with spasticity of

the arms and legs, and generalized hyperreflexia in the

ABSENCE OF SENSORY signs and symptoms may be seen.

Patients never complain of sensory symptoms (e.g.,numbness and tingling). If they do, forget aboutmotor neuron disease. It may be a spinal cord

compression.

Atrophic weakness spreads to the tongue, pharyngeal

and laryngeal muscles

Present as difficulty of swallowing, stridor, dysarthriaSphincteric control is preserved despite leg spasticity and

weakness

LEGEND

Normal text : lecture and recording

Italics: Adams and Victors Principles of Neurology

MOTOR SYSTEM DISEASESDr. Emmanuel Eduardo 01.28.11

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50% of patients die within 3 years and 90% within 6 years

PROGRESSIVE MUSCULAR ATROPHY (PMA)

More common in men (4:1)

Tends to progress slower than ALS (survival in some

cases up to 20 years)

Anterior horn cells are involved

Manifestations are purely related to the Lower Motor

Neuron!!

weakness and atrophy initially of hand musclesusually symmetrical

slowly advancing to involve whole limb, proximal

more than distal

fasciculations and cramps are invariably present

NO Upper Motor Neuron signs like Babinski,

hyperreflexia and spasticity

PROGRESSIVE BULBAR PALSY

Manifestations at the oropharyngeal area before the

signs become generalized

Feeding is problematic. Usually patients need to be fed

by a gastric tube directly because this ends up a longaffair. You need to do Percutaneous Endoscopic

Gastrescopy (PEG) to divert the feeding.

A patient may also need tracheostomy to breathe

because difficulty of breathing occurs early

Just like ALS, fast progression with death occurring within

2 to 3 years

Therefore, if you are able to diagnose a patient tohave this disease, talk to him and his family about

end of life, because there is no cure and life support

will be difficult. (Be straightforward about this!)

Note: This has the fastest progression of the 4 majortypes of motor neuron disease because patients

present with dysarthria and tongue fasciculations

making breathing and feeding difficult.

First and dominant symptoms are due to weakness and

atrophy of muscles innervated by motor nuclei in the

lower brainstem, i.e., muscles of the tongue, jaw, face,

pharynx and larynx.

Articulation, mastication, and deglutition eventually

become problems

Jaw jerk is exaggerated with spasticity of oropharyngeal

muscles

Pseudobulbar signs

Hyperactive facial and gag reflexes Lack of muscle atrophy Emotional control is impairedspasmodic crying and

laughing (i.e., patient is laughing one moment and

crying the next)

Ocular muscles and the abducens nerve (for some

reason) are NOT involved so if you have a CN VI

problem (such as diplopia) consider another diagnosis

Eventually, weakness involves the respiratory muscles

biggest problem in these patients

After a few months, signs and symptoms of ALS appear

PRIMARY LATERAL SCLEROSIS (PLS)

Present with corticospinal signs only (i.e. only UMN signsand symptoms)

Begins insidiously in the fifth or sixth decade (or older)

Starts with stiffness of one leg

Involves the other leg eventually leading to slowing of

gait

Spasticity of the legs dominate the degree of weakness

Severe spastic paraparesis

As the years pass, the upper limbs are involved and the

speech takes a spastic tone (slow, thick, and indistinct

speech sir described it as an increased effort to speak,

but not like dysarthria)

There is degeneration of the Betz cells. On MRI, you will

appreciate corticospinal tract atrophy.

Motor neurons in the brainstem and the spinal cord, as

well as the anterior horn cells preserved.

Pathology of Motor Neuron Disease

Loss of large Alpha motor neurons in the motor cortex

(Betz cells), motor nuclei of the lower brainstem, and

anterior horns of the spinal cord

Degeneration of the corticospinal tract

Etiology of Motor Neuron Disease

The pathogenesis of the sporadic form (more than 90%

of cases) is not known

This is why attempts at a cure for these diseaseshave failed thus far.

The familial variety

, which accounts for 10% of cases: showed mutation in the gene that encodes the

cytosolic enzyme Cu-Zn superoxide dismutase

(SOD1)

Mutant SOD1 protein aggregates cause excitotoxicglutaminergic activity, which in turn causes motor

cells to fire all the time

Mitochondrial dysfunction occurs eventually fromexcess use

Cell goes to apoptosis soon afterDiagnostic Tests

Electrodiagnostic Test (EMG- NCV) is the most helpful.

Muscle biopsy sometimes helpful in showing neurogenicdenervation

CSF exam usually unremarkable. So do not do a lumbar

tap!

MRI may show slight atrophy of the motor cortices and

degeneration of the motor tracts. Changes are

nonspecific (you see this in normal elderly people)

CPK levels maybe mildly elevated in rapidly progressive

disease due to muscle fiber breakdown from denervation

but otherwise unremarkable. Elevated CPK levels can

lead to misdiagnosis of muscle disease so be sure to rule

it (i.e. muscle disease) out.

EMG-NCV Findings

Widespread fibrillations and fasciculations

(active denervation/with massive loss of motor neuron)

Large motor unit potentials (reinnervation) -

compensation of body. Eventually this is lost because of

massive motor neuron loss.

Low amplitude compound muscle action potentials with

normal conduction velocities

NORMAL SENSORY CONDUCTION! -- If you find

abnormalities here, you are probably dealing with

peripheral neuropathy.

Treatment

Nothing was found to cure the disease. Treatment so far is

aimed at supportive measures.

Riluzole

Anti-glutamate agent

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