Collection of Blood Samples for DNA in Motor Neuron Disease

OBJECTIVE:

The causes of sporadic motor neuron diseases, primary lateral sclerosis (PLS) and amyotrophic
lateral sclerosis (ALS) are unknown. Genes have been identified for some forms of familial
motor neuron diseases. We don't know whether genes also play a role in sporadic motor neuron
disease, for example through risk-factor genes or by the interaction of multiple genes as a
complex genetic disorder. Identification of genetic contributions to sporadic motor neuron
diseases requires analysis of DNA from patients.

The goal of this protocol is to collect blood samples from patients with motor neuron disease
for creation of cell lines to bank in a repository created through an NINDS initiative. The
cell lines will be used for DNA extraction. The repository provides anonymized samples of
patient DNA or cell lines to investigators who are seeking to define genetic causes,
contributions, and susceptibilities to neurological disorders. DNA and cell lines created
from the blood sample are stripped of patient identifiers and stored indefinitely. A limited
amount of clinical data, termed the clinical data elements, will be available for each coded
sample. The samples will only be available for research. The results of testing will not be
communicated to the patient.

STUDY POPULATION:

All patients will be enrolled in a primary protocol for the study of motor neuron diseases at
NIH. This protocol will serve as a secondary protocol for sample collection and reporting of
clinical data elements. Patients with Primary lateral sclerosis must meet the diagnostic
criteria for PLS proposed by Pringle and patients with ALS must fulfill the revised El
Escorial criteria for probable or definite ALS.

DESIGN:

Determination of diagnosis and eligibility will be carried out as part of the primary
protocol. Patients will be informed of the DNA sample repository and its purpose. After
informed consent is obtained, 2 tubes of blood will be drawn and assigned a unique identifier
code. The coded samples, and a clinical data element form will then be sent to the
repository, which will extract DNA and prepare cell lines. The identities of the subjects
will not be stored. An aliquot of the sample will be forwarded to the associate investigator
to look for disease associations with genetic markers.

OUTCOME MEASURES:

There is no specific outcome measure for this protocol. The samples will be made accessible
to a wide variety of researchers seeking to determine the causes of motor neuron diseases and
other neurological disorders through the repository's contract with NINDS.

- PRIMARY LATERAL SCLEROSIS INCLUSION CRITERIA:

Patients with PLS, aged 18 and older, must meet the diagnostic criteria proposed by Pringle
(1992), incorporating Santa Clara (2004) consensus for pure PLS.

Clinical:

- Insidious onset in adulthood, progressive course

- No family history

- Disease duration greater than 3 years without lower motor neuron clinical signs

- Clinical signs restricted to corticospinal/corticobulbar tract dysfunction

Imaging:

- Brain MRI normal (except cortical atrophy)

- Normal cervical spine

- Negative chest X-ray, negative mammograms in women

EMG after 3 years, but within last 3 years, showing no active denervation.

Normal serological studies for serum chemistry, Vitamin B12, Vitamin E levels, very
long-chain fatty acids.

Negative serology for syphilis, Lyme disease, HTLV 1 and 2.

AMYOTROPHIC LATERAL SCLEROSIS INCLUSION CRITERIA:

Patients with ALS, aged 18 and older, must fulfill the revised El Escorial criteria for
probable or definite ALS.

- Probable ALS: Upper and Lower motor neuron signs are present in more than two regions,
but some UMN signs must be rostral to LMN signs.

- Definite ALS: Upper and Lower motor neuron signs are present in more than three
regions.

EXCLUSION CRITERIA: