Full Text PA-95-017

SYRINGOMYELIA

NIH GUIDE, Volume 24, Number 1, January 13, 1995

PA NUMBER:  PA-95-017

P.T. 34

Keywords: 
  Neuromuscular Disorders 


National Institute of Neurological Disorders and Stroke
National Institute of Child Health and Human Development

PURPOSE

The National Institute of Neurological Disorders and Stroke (NINDS)
and the National Center for Medical Rehabilitative Research (NCMRR)
of the National Institute of Child Health and Human Development
(NICHD) announce the issuance of a program announcement to notify the
scientific community of their interest in the submission of research
grant applications concerning syringomyelia.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2000,"
a PHS-led national activity for setting priorities.  This PA,
Syringomyelia, is related to the priority areas of chronic disabling
conditions.  Potential applicants may obtain a copy of "Healthy
People 2000" (Full Report:  Stock No. 017-001-474-0), or "Healthy
People 2000" (Summary Report:  Stock No. 017-001-00473-1) through the
Superintendent of Documents, Government Printing Office, Washington,
DC 20402-9325 (telephone 202-783-3238).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by foreign and domestic, for-profit and
non-profit organizations, public and private, such as universities,
colleges, hospitals, laboratories, units of State and local
governments, and eligible agencies of the Federal government.
Foreign institutions are not eligible for First Independent Research
Support and Transition (FIRST) (R29) awards, program projects (P01),
and center grants (P50).  Racial/ethnic minority individuals, women,
and persons with disabilities are encouraged to apply as principal
investigators.

MECHANISM OF SUPPORT

The mechanisms of support will be the research project grant (R01),
program project (P01), center grants (P50), (NINDS only), and FIRST
Award (R29).  Prospective applicants are encouraged to communicate
with the NINDS or NICHD program contacts listed under INQUIRIES
regarding the appropriate funding mechanism.

RESEARCH OBJECTIVES

Summary

Syringomyelia may be defined as a chronic progressive degenerative
disorder of the spinal cord.  Pathologically, syringomyelia is
characterized by formation of a syrinx, or fluid-filled cyst, in the
spinal cord, which expands and elongates over time.  Clinically,
there is damage to the spinal cord, which results in chronic pain,
weakness in the extremities, and loss of sensation.  There are two
main forms of syringomyelia, congenital and acquired.  In most cases,
there is a congenital abnormality of the brain, the type I Chiari
malformation, where the cerebellar tonsils protrude into the
subarachnoid space at the level of the foramen magnum.  Although this
abnormality is thought to be present at birth, the onset of
syringomyelia does not occur until adulthood.  A syrinx may form in
the cervical region of the spinal cord.  About 50 percent of adults
with Chiari I malformations will develop syringomyelia.  The second
major form of syringomyelia occurs as a complication of trauma,
inflammation, or a tumor.  In this case, the syrinx forms at the site
of the injury.  The diagnosis of syringomyelia has been greatly
facilitated by the use of magnetic resonance imaging (MRI).  Once the
syrinx has been confirmed, the patient and doctor can decide the
course of treatment based on symptoms and size of the syrinx.

The treatment of syringomyelia is a subject of much debate among
neurosurgeons.  Surgical treatment could involve decompression of the
foramen magnum, with or without a dural graft, to relieve the
pressure on the spinal cord.  In many cases, this will collapse the
syrinx, and prevent progression of the disease.  Some surgeons prefer
to place a shunt in the cavity, to drain the syrinx and prevent its
re-expansion.  There are complications because of infection and shunt
blockage.  In all surgical treatments, there are complications due to
scarring and possible tethering of the cord.  Unfortunately, in many
cases there is no reversal of the symptoms already present.  There is
also no consensus among neurosurgeons about the time course for
treatment.  Some prefer to treat all syrinxes immediately hoping to
prevent some of the more serious symptoms.  Others follow the more
cautious route and wait to see if the syrinx will expand.  These
patients may be followed by electrophysiological testing to determine
if there are presymptomatic indications that the syrinx is expanding.
In both cases, there are risks.  Some individuals will be treated who
would never have developed syringomyelia.  Others will develop the
symptoms and life-long disability associated with syringomyelia
because of delay in treatment.  A controlled clinical study has not
been done to study the short- and long-term outcomes of the various
treatment options.  This information would be very important for
determining which treatment is appropriate for each individual.

Although the technologies available are making it easier to diagnose
syringomyelia, there is not enough known about the causes.  MRI has
allowed the physician to identify syrinxes in the patient at a very
early time, before the onset of symptoms.  In some patients, there is
never a progression to syringomyelia.  In other patients, the syrinx
expands and symptoms appear.  The trigger that causes the syrinx to
expand is not known.

Several research groups are working to develop animal models of
syringomyelia so that studies can be done to understand the basic
pathophysiology of syrinx formation and expansion.  Spinal cord
cavitation can be induced by injection of kaolin into the spinal cord
in mice.  Other agents, such as excitatory amino acids, are known to
induce cavitation.  Various manipulations can be easily performed in
animal models that cannot be done in humans.  Animal models will be
important for fully understanding syrinx formation and expansion in
syringomyelia.

The NINDS encourages submission of research grant applications in the
area of syringomyelia.  Some areas of interest include, but are not
limited to:

o  Comparative studies of spinal cord structure and function between
normal and syringomyelia subjects, including anatomy, pharmacology,
and physiology

o  MRI flow studies, electrophysiology, and metabolic studies of the
cord in syringomyelia patients

o  Clinical studies of syringomyelia that incorporate information
about treatment procedures and short- and long-term outcomes

o  Clinical studies to determine the pathophysiology of the various
types of syringomyelia, including Chiari Type I and Type II, and
post-traumatic

o  Clinical trials to assess various treatment options for
syringomyelia

o  Studies on biomaterials, to determine which types of sutures,
shunts, and dura grafting materials are most appropriate, and to
develop new types of biomaterials

o  Studies to improve imaging technologies, toward real time imaging
and non-invasive pulse pressure measurements

o  Studies to determine the causes of gliosis toward prevention of
scarring and cord tethering

o  Assessment of existing animal models to determine their usefulness
for studies of syringomyelia.

o  Development of new animal models of syringomyelia

In addition, the NCMRR is interested in research areas including, but
not limited to:

o  Studies to develop and validate ecologically appropriate,
sensitive, and practical functional status measures to track
functional changes during conservative management or evaluate the
effects of surgical interventions in cases of syringomyelia

o  Studies of surgical and non-surgical interventions that reduce
pain associated with syringomyelia

o  Prospective studies using imaging techniques, behavioral
observation and self-report to study the natural course, prevalence,
and risk factors that predict acute episodic and gradual functional
loss in people with syringomyelia

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN
SUBJECTS

It is the policy of the NIH that women and members of minority groups
and their subpopulations must be included in all NIH supported
biomedical and behavioral projects involving human subjects, unless a
clear and compelling rationale and justification is provided that
inclusion is inappropriate with respect to the health of the subjects
or the purpose of the research.  This new policy results from the NIH
Revitalization Act of 1993 (Section 492B of Public Law 103-43) and
supersedes and strengthens the previous policies (Concerning the
Inclusion of Women in Study Populations, and Concerning the Inclusion
of Minorities in Study Populations), which have been in effect since
1990.  The new policy contains some provisions that are substantially
different from the 1990 policies.

All investigators proposing research involving human subjects should
read the "NIH Guidelines For Inclusion of Women and Minorities as
Subjects in Clinical Research," which have been published in the
Federal Register of March 28, 1994 (FR 59 14508-14513) and reprinted
in the NIH Guide for Grants and Contracts, Volume 23, Number 11,
March 18, 1994.

Investigators also may obtain copies of the policy from the program
staff listed under INQUIRIES.  Program staff may also provide
additional relevant information concerning the policy.

APPLICATION  PROCEDURES

Applications are to be submitted on the grant application form PHS
398 (rev. 9/91) and will be accepted at the standard application
deadlines as indicated in the application kit.  Application kits are
available at most institutional offices of sponsored research and may
be obtained from the Office of Grants Information, Division of
Research Grants, National Institutes of Health, Westwood Building,
Room 449, Bethesda, MD 20892, telephone 301-710-0267.  The title and
number of the program announcement must be typed in Section 2a on the
face page of the application.

Applicants for program project grants or centers should request a
copy of the NINDS Guidelines: Program Project and Research Center
Grants (rev. May 1994), from the NINDS program staff listed under
INQUIRIES.  Receipt dates for new research project grant applications
and FIRST Awards (R01 and R29, respectively) and for program project
and center grant applications (P01 and P50, respectively) are
February 1, June 1, and October 1.

FIRST award applications must include at least three sealed letters
of reference attached to the face page of the original application.
FIRST applications submitted without the required number of reference
letters will be considered incomplete and will be returned without
review.

The completed original application and five legible copies must be
sent or delivered to:

Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892**

If the application is for a program project or center grant, send the
original and three copies to the Division of Research Grants.  Send
an additional two copies of the program project (P01) or center grant
(P50) application to Dr. Judy Small at the address listed under
INQUIRIES.

REVIEW CONSIDERATIONS

Applications will be assigned on the basis of established Public
Health Service referral guidelines.  Applications will be reviewed
for scientific and technical merit in accordance with the standard
NIH peer review procedures.  Following scientific-technical review,
the applications will receive a second-level review by the
appropriate national advisory council.

As part of the initial merit review, a process (triage) may be used
by the initial review group in which applications will be determined
to be competitive or non-competitive based on their scientific merit
relative to other applications.  Applications judged to be
competitive will be discussed and be assigned a priority score.
Applications determined to be non-competitive will be withdrawn from
further consideration and the Principal Investigator and the official
signing for the applicant organization will be notified.

Review Criteria

o  scientific, technical, or medical significance and originality of
proposed research;

o  appropriateness and adequacy of the experimental approach and
methodology proposed to carry out the research;

o  qualifications and research experience of the Principal
Investigator and staff, particularly, but not exclusively, in the
area of the proposed research;

o  availability of the resources necessary to perform the research;

o  appropriateness of the proposed budget and duration in relation to
the proposed research;

o  Adequacy of plans to include both genders and minorities and their
subgroups as appropriate for the scientific goals of the research.
Plans for the recruitment and retention of subjects will also be
evaluated.

The initial review group will also examine the provisions for the
protection of human and animal subjects and the safety of the
research environment.

AWARD CRITERIA

Applications will compete for available funds with all other approved
applications assigned to that Institute or Center.  The following
will be considered in making funding decisions:  quality of the
proposed project as determined by peer review, availability of funds,
and program priority.

INQUIRIES

Inquiries are encouraged.  The opportunity to clarify any issues or
questions from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Dr. Judy A. Small
Division of Convulsive, Developmental, and Neuromuscular Disorders
National Institute of Neurological Disorders and Stroke
Federal Building, Room 8C04
7550 Wisconsin Avenue MSC 9165
Bethesda, MD  20892-9165
Telephone:  (301) 496-5821
FAX:  (301) 480-1080
Email:  [email protected]

Dr. David B. Gray
Deputy Director
National Center for Medical Rehabilitative Research
National Institute of Child Health and Human Development
Building 6100E, Room 2A03
6100 Executive Boulevard, MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 402-2242
FAX:  (301) 402-0832
Email:  [email protected]

Direct inquiries regarding fiscal matters to:

Mr. King P. Bond, Jr.
Grants Management Branch
National Institute of Neurological Disorders and Stroke
Federal Building, Room 1004
Bethesda, MD  20892-9190
Telephone:  (301) 496-9231
FAX:  (301) 402-0218
Email:  [email protected]

Ms. Mary Ellen Colvin
Office of Grants and Contracts
National Institute of Child Health and Human Development
Building 6100E, Room 8A17
6100 Executive Boulevard, MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 496-1303
FAX:  (301) 402-0915
Email:  [email protected]

AUTHORITY AND REGULATIONS

This program is described in the Catalogue of Federal Domestic
Assistance, No. 93.853, Clinical Research Related to Neurological
Disorders, and 93.854, Biological Basic Research in the
Neurosciences.  Awards are made under the authorization of the Public
Health Service Act, Title IV, Part A (Public Law 78-410, as amended
by Public Law 99-158, 42 USC 241 and 285) and administered under PHS
grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74.
This program is not subject to Intergovernmental review requirements
of Executive Order 12372 or Health Systems Agency review.

The Public Health Service (PHS) strongly encourages all grant
recipients to provide a smoke-free workplace and promote the non-use
of all tobacco products.  This is consistent with the PHS mission to
protect and advance the physical and mental health of the American
people.

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