Validation of Biomarkers in Amyotrophic Lateral Sclerosis (ALS)

Researchers tested what changes happen in volunteers with ALS that can be seen in the blood
and what changes are unique to ALS and are different from those found in healthy volunteers
and volunteers with neurological diseases other than ALS. These changes are called
biomarkers. Biomarkers for ALS have been found in blood collected in earlier phases of this
study. Biomarkers are non-genetic elements in your blood that may help to make diagnosing
ALS easier. In the next phase, comparison of these changes in the blood of volunteers with
ALS and without ALS will be used to confirm these biomarkers and to develop a tool to
diagnose and monitor progression of ALS.

1. ALS Volunteers

Inclusion Criteria:

- Diagnosis of possible (excluding volunteers with UMN signs ONLY), probable,
probable-laboratory supported, or definite ALS, either sporadic or familial
according to revised El Escorial criteria

- Disease duration of less than or equal to two years from symptom onset

- Age 30-80 years at the time of disease onset

- Ability to provide informed consent

- Ability to comply with study procedures

- Medically safe to have lumbar puncture (lumbar puncture volunteers only)

Exclusion Criteria:

- Clinical evidence of chronic liver or renal failure

- Presence of a bleeding disorder, problems with CSF pressure, allergy to local
anesthetics, or a topical or other skin infection at the LP site (lumbar
puncture volunteers only)

- Use of any anti-platelet or anticoagulant drugs, such as plavix, aggrenox,
ticlid, warfarin or coumadin (lumbar puncture volunteers only)

2. Suspected ALS (PMND) Volunteers

Inclusion Criteria:

- Diagnosis of suspected ALS defined as presence of UMN or LMN signs alone and the
diagnosis of Clinically Probably Laboratory-Supported ALS CANNOT be proven by
evidence in clinical grounds in conjunction with electrodiagnostic,
neurophysiologic, neuroimaging or clinically laboratory studies

- Disease duration of less than or equal to four years from symptom onset

- Age 30-80 years at time of disease onset

- Ability to provide informed consent

- Ability to comply with study procedures

- Medically safe to have lumbar puncture (lumbar puncture volunteers only)

Exclusion Criteria:

- Clinical evidence of chronic liver or renal failure

- Genetically confirmed diagnosis of hereditary spastic paraparesis or spinal
motor atrophy (SMA) disease

- Presence of a bleeding disorder, problems with CSF pressure, allergy to local
anesthetics, or a topical or other skin infection at the LP site (lumbar
puncture volunteers only)

- Use of any anti-platelet or anticoagulant drugs, such as plavix, aggrenox,
ticlid, warfarin or coumadin (lumbar puncture volunteers only)

3. Neurological Disease Mimic Volunteers

Inclusion Criteria:

Diagnosis of one of the following:

Pure Lower Motor Neuron Disease (LMND) mimics:

- Multi-focal motor neuropathy

- Autoimmune motor neuropathy

- Cervical or lumbosacral radiculopathies

Peripheral mononeuropathies:

- Ulnar neuropathy

- Carpal tunnel syndrome/median neuropathy

- Peroneal neuropathy

- Sciatic neuropathy

- Spinal muscular atrophy

- Spinobulbar muscular atrophy (Kennedy's disease)

- Charcot Marie-Tooth Disease (CMT)

Pure Upper Motor Neuron Disease (UMND) mimics:

- Cervical myelopathy

- Multiple sclerosis

- Hereditary spastic paraparesis

- Age 30-80 years

- Ability to provide informed consent

- Ability to comply with study procedures

- Medically safe to have lumbar puncture (lumbar puncture volunteers only)

Exclusion Criteria:

- Diagnosis of suspected, possible, probable or definite ALS either sporadic or
familial

- Presence of positive family history of ALS

- Clinical evidence of chronic renal or liver failure

- Presence of a bleeding disorder, problems with CSF pressure, allergy to local
anesthetics, or a topical or other skin infection at the LP site (lumbar
puncture volunteers only)

- Use of any anti-platelet or anticoagulant drugs, such as plavix, aggrenox,
ticlid, warfarin or coumadin (lumbar puncture volunteers only)

4. Healthy Control Volunteers Inclusion Criteria

- Absence of a known neurological disorder.

- Age 30 - 80 years.

- Ability to provide informed consent.

- Ability to comply with study procedures.

- Medically safe to have lumbar puncture.

Exclusion Criteria:

- History of ALS, myopathy, neuropathy, ALS mimic disorder or other neurodegenerative
disease.

- Presence of positive family history of ALS.

- Clinical evidence of chronic liver or renal failure.

- Presence of bleeding disorder, problems with CSF pressure, allergy to local
anesthetics, or a topical or other skin infection at the LP site (LP research
volunteers only).

- Research participant must not be taking anti-platelet or anticoagulant drugs, such as
plavix, aggrenox, ticlid, warfarin or coumadin (LP research volunteers only).