Screening and Natural History: Primary Lateral Sclerosis and Related Disorders

Objective:

The objectives of this protocol are:

- to develop and maintain a repository of clinically characterized patients with primary
lateral sclerosis for future research protocols,

- to characterize the natural history of neurodegenerative disorders with corticospinal
neuron degeneration,

- to investigate proposed etiologies, risk factors, and biomarkers for the development of
these disorders and for disease progression

Study Population:

240 patients with adult-onset progressive spasticity with a diagnosis of primary lateral
sclerosis or related upper motor neuron disorder

Design:

Patients who have been referred by physicians for primary lateral sclerosis will undergo a
screening evaluation at the first visit. The screening visit will include review of outside
medical records, neurological examination, and diagnostic testing to determine possible
causes of spasticity. Patients fulfilling the clinical criteria for primary lateral sclerosis
by history or examination will be followed to determine the natural history of this disorder.
Measures of motor and cognitive function will be made at baseline and follow-up visits to
follow clinical progression. Magnetic resonance imaging will be carried out to determine if
imaging changes occur over time. Blood samples may be collected for measurement of potential
etiologies of PLS, including risk factor genes. Patients identified in this protocol who are
eligible for other research protocols will be invited to participate in additional protocols.

Outcome Measures:

Clinical progression will be documented by measures of finger-tapping, timed gait, speech.
The association between clinical progression and MRI measures will be assessed as a secondary
outcome.

- INCLUSION CRITERIA:

- Age 18 years of age or older

- Adult onset of progressive spasticity

- No family history of a similar disorder

- Able to provide consent or with a legally-authorized representative who can provide
consent

EXCLUSION CRITERIA:

- History of stroke, cerebral palsy, traumatic brain injury or other known etiology of
spasticity

- Non-neurological disorders producing muscle stiffness, such as fasciitis or
rheumatological conditions

- Disorders in which pain limits the ability to move muscles, such as fibromyalgia or
complex regional pain syndromes

- Profound weakness of voluntary movement

- Inability to travel to NIH

- Anticoagulation will be an exclusion for needle EMG studies

- Implanted devices or metal fragments in the brain or spinal cord will be an exclusion
for MRI scanning