Diagnosis

Presentation

The weakness of ALS usually begins focally (in one place) in one of the body segments. Unilateral (one side of the body) onset in an arm or leg is the most common presentation (80%). Bulbar (affecting muscles of the face, speech, and swallowing) onset is less common (20%). Respiratory muscle onset is least common (<1%).
Once it starts the weakness is relentlessly progressive. When muscle weakness begins in a limb it may start in one or a few muscles. It then spreads to other muscles within the same limb. Then it spreads elsewhere.

There is a common pattern to this spread of weakness that is noted about 70% of the time:
A.    Arm onset
1.    Then spread to opposite arm
2.    Then spread to leg on same side as initial arm
3.    Then spread to opposite leg
4.    Then spread to bulbar muscles
B.    Leg onset
1.    Then spread to opposite leg
2.    Then spread to arm on same side as initial leg
3.    Then spread to opposite arm
4.    Then spread to bulbar muscles
C.    Bulbar onset
1.    Then spread to one of the arms

ALS is very different from one person to the next. Common differences include: site of initial onset; location of weakness in the site of initial onset (which muscles are involved); pattern of spread of weakness within the initial site of onset; pattern of spread from segment to segment; speed with which progression occurs; relative predominance and distribution of UMN, LMN, or combined UMN and LMN symptoms and signs; and when life threatening symptoms and signs occur.

Diagnostic Evaluation
Currently there is no single diagnostic test for ALS. Clinical diagnosis depends upon a history, physical examination, and laboratory and radiographic evaluation that is consistent with ALS and excludes other diseases that may mimic ALS.

Historical Features
ALS presents with the following: progressive weakness over time, spread of weakness from segment to segment, UMN, LMN, or combined UMN and LMN symptoms, and lack of exclusionary symptoms

Physical Examination Features
ALS patients present with UMN, LMN, or combined UMN and LMN signs in one or more body segments. They lack exclusionary signs.

Laboratory and Radiographic Features
Tests used to exclude disorders of the central (brain and spinal cord) and peripheral (spinal nerves, nerves, muscles) nervous system that may mimic ALS include: complete blood count, comprehensive metabolic panel, creareatine phospokinase (CPK) (but may also be elevated in ALS), thyroid function tests, serum protein electrophoresis (but elevation of serum antibodies [paraproteins] may also be seen in up to 10% of ALS), anti-GM1 antibodies (present in about half of patients with multifocal motor neuropathy, a disorder that mimics LMN findings of MND), Lyme disease antibodies, syphilis antibodies, erythrocyte sedimentation rate, anti-nuclear antibodies, angiotensin converting enzyme, serum and urine heavy metals (elevated lead levels indicative of excessive lead exposure may produce an arm predominant motor neuropathy, a disorder that mimics LMN findings of MND).

Cerebropinal fluid (CSF) analysis show normal values of glucose, white blood cell, red blood cell, and antibody pattern. However, mild elevations of protein, usually less than 100, can be seen in ALS.

Imaging studies of the nervous system are used to exclude disorders of the brain and or spine that may mimic ALS. An MRI is preferable to a CT scan. An MRI of the brain is usually normal in ALS but it may sometimes demonstrate increased signal in the motor strip in the brain and corticospinal tracts of the spinal cord. An MRI of the cervical and lumbosacral spines will likely be abnormal in individuals above the age of 40.

Electromyography (EMG) and nerve conduction studies (NCS) are used to evaluate disorders of muscle and nerve including LMN abnormalities of ALS. Findings expected in ALS are ongoing and chronic denervation (loss of nerve supply of muscle) in muscles that are weak on physical examination. The tests may also detect abnormalities in muscles that are not weak on physical examination
Muscle biopsy of a weak muscle may confirm microscopic evidence of changes that occur after a muscle loses its nerve supply. It helps exclude other potential causes of muscle weakness. It is usually not necessary if the EMG or NCS demonstrates clear evidence of denervation.

Level of diagnostic certainty for ALS
If the history, physical examination, and laboratory and radiographic evaluation suggest diagnosis of ALS, the degree of diagnostic certainty is defined by the presence and location of both UMN and LMN signs.

The El Escorial Criteria is used to determine how likely it is for someone to have ALS. Depending on how the criteria is fulfilled one is classified under one of the following categories:
1.    Clinically suspected ALS
2.    Clinically possible ALS
3.    Clinically probable ALS – Laboratory Supported
4.    Clinically probable ALS
5.    Clinically definite ALS

Variants of ALS include the following:
1.    Progressive Muscular Atrophy (PMA) is defined by the presence of LMN without UMN signs. Throughout the clinical course some patients may never develop UMN signs. Often, however, UMN signs do eventually develop. If so the name is changed to LMN onset ALS.
2.    Primary Lateral Sclerosis (PLS) is defined by the presence of UMN without LMN signs. Throughout the clinical course some patients may never develop LMN signs. Often, however, LMN signs do eventually develop. If so the name is changed to UMN onset ALS.
3.    Progressive Bulbar Palsy is defined by the presence of UMN, LMN, or combined UMN and LMN signs in bulbar muscles. Throughout the clinical course some patients may never develop signs outside of bulbar muscles. Often, however, UMN, LMN, or combined UMN and LMN signs do eventually develop in other segments. If so the name is changed to bulbar onset ALS.