Cerebral Palsy
Workshop on the Definition and Classification of Cerebral Palsy
July 11-13, 2004, Bethesda, MD
What are the problems with the present definitions and how can they be improved?
The Clinical Genetic Perspective: Hugo W. Moser, M.D.
In the recently published “Practice Parameters on the Diagnosis Assessment of the
Child with Cerebral Palsy” (Ashwal et al, Neurology 61:851-863, 2004) Cerebral
Palsy is defined as “a disorder of aberrant control of movement and posture,
appearing early in life secondary to a Central Nervous System Lesion or dysfunction
that is not a result of a recognized progressive or degenerative brain disease.”
I recommend that this definition should be changed by removing the exclusion of
recognized progressive or degenerative brain disease for the following reasons:
1. Distinction between a static and a progressive brain disease may be difficult to
distinguish clinically in a young child. Static brain lesions may be associated with
apparent clinical progression, particularly in children with dystonia.
2. Conversely many genetic disorders that might be classified as a progressive or
degenerative disorder can masquerade initially as non-progressive cerebral palsy
under the current classification. While these disorders are rare individually, an
increasing number of such disorders are being recognized and in the aggregate their
number is significant. Examples of such disorders are:
Disorders of amino acid and organic acid metabolism such as glutaric aciduria type 1
Lesch-Nyhan syndrome
Sjogren Larssen syndrome
Metachromatic Leukodystrophy
Globoid leukodystrophy
Pelizaeus-Merzbacher disease variants
Urea cycle disorders such as arginase deficiency
Creatine transporter deficiency
Biotinidase deficiency
Ataxia telangiectasia
Dopa sensitive dystonia
Rett syndrome
Hereditary spastic paraparesis with defined molecular defects
Disorders of neuronal migration
3. The early recognition of such disorders, that is their early distinction from “static
cerebral palsy,” can have profound therapeutic implications for the child. Glutaric
aciduria type 1, biotinidase deficiency, dopa sensitive dystonia, and the urea cycle
disorders are examples, or for genetic counseling, as in the leukodystrophies and the
Lesch Nyhan syndrome.
4. Genetic factors contribute to the susceptibility for “static” lesions that lead to
cerebral palsy. Examples of this are coagulation defects with the factor V Leiden
mutation. The studies of Nelson et al. (Ann Neurol 44:665, 1998) have shown
cytokine abnormalities in blood samples obtained at birth from infants that later
developed cerebral palsy as it is currently defined. The mechanisms involved are not
understood, but it is possible that predisposition for these pathogenetic changes is
influenced jointly by environmental and genetic factors. Recent studies in other fields,
such as cerebrovascular disease, have identified mutations that increase the risk for a
variety of strokes. Analogous correlations may be found to exist in cerebral palsy.
This would further blur the distinction between static and progressive or degenerative
disease cerebral palsy.
5. The capacity to determine the precise cause of cerebral palsy with non-invasive and
precise techniques is expanding exponentially. The combination of neuroimaging
studies with biochemical and molecular techniques is particularly promising. The
precision of these techniques is increasing and the cost is expected to diminish.
Furthermore, therapeutic interventions are becoming more effective. It is likely that
these developments will alter the cost-benefit ratio for the performance of molecular
and biochemical studies. In the previously cited report (Ashwal et al 2004) the
Quality Standard Task Force did not recommend the performance of metabolic or
molecular studies unless there were specific leads that suggested their existence. It is
likely that this will change and that a larger series of studies will be performed in all
children with Cerebral Palsy. There are two reasons for this: 1) as already noted, it is
likely that the expense of these studies will diminish; 2) recent experience with
several of these disorders indicates that if diagnosis is deferred until the characteristic
“classic” symptom complex develops, therapy may no longer be effective. Delays in
achieving the correct diagnosis thus may have profound adverse consequences for the
child.
Recommendations for the definition and classification
I recommend that the designation of cerebral palsy be retained for disorders
associated with aberrant control of movement and posture appearing in early life
secondary to Central Nervous System Lesions or dysfunction. The term describes a
significant set of abnormalities with a reasonably circumscribed set of symptoms and
handicaps that are well known to the public and to health care providers and it does
not have the perjorative implication associated with terms such as mental retardation
or degenerative disease.
I, therefore, recommend that the designation of cerebral palsy continue to be applied
to those patients be coupled with 1) description of major characteristics (diplegia,
hemiplegia tetraplegia, dyskinesia, ataxia); 2) location of lesion as defined by
neuroimaging studies, and; 3) etiology (anoxia, asphyxia, hemorrhage, hematological
disorders, infections, toxic, trauma, manformations, metabolic or genetic, or
unknown). The design of such a classification requires further study. It may not be
feasible until the availability and costs of the appropriate tests become more
favorable. Implementation of this more detailed classification will increase the cost of
initial evaluation, but I believe that it will be cost-effective in the long run, since it
will provide the opportunity for more specific and effective therapies.