Advances in neonatal neurology continue to
focus on potentially modifiable factors during the neonatal
period, which can contribute to the development of Cerebral
Palsy. Many of these studies focus on the role of excitable
amino acids and their role in neurological injury. The hope is
that more can be done in the neonatal period to prevent the
permanent neurologic deficit resulting in CP.
In the meantime,
however, Amino Acid Therapy, now used extensively in Russia, is
a method of treating brain damage and abnormality developed by
Professor Alexander Khokhlov, a Russian Professor of
biochemistry and neurology. Other clinics in the Czech Republic,
Cyprus, London and New Zealand are now also administering this
therapy.
Amino acid therapy
consists of the oral or intravenous administration of one or
more essential amino acids. Savin and Khokhlov studied the
effects of amino acid therapy on 84 infantile cerebral palsy
patients undergoing treatment from February 1994 to February
1996.
All patients completed
repeated courses of treatment, lasting from 4 to 8 weeks
(an average of 5
weeks).
Thirty-nine subjects
(46.43%)
received two courses of treatment; 20 subjects
(23.81%) had 3 courses; 9
subjects
(10.7%)
took 4 courses; another 9 subjects
(10.7%)
received 5 courses; 6 patients
(7.1%)
had 6 courses; and 1 female patient
(1.19%)
underwent 7 courses of treatment. Accordingly, 53.56% of
patients received 3 or more therapy courses. Duration of
follow-up ranged from 0.5 year to 2 years.
In the patients'
clinical histories, spastic forms of the disease were
predominant
(58 patients or 69.04%, including 19 patients with spastic
diplegia or Little's disease).
Spastic tetrapareses were identified in 24 patients, hemipareses
in 15, atonic-static syndrome in 6 patients, hyperkinetic form
was recorded in 13 subjects, among whom hyperkinesias in 6 cases
combined with central paralyses.
Pronounced intellectual
disorders were found in 7 patients who had non-severe motor
defect background. Among 17 subjects
(20.23%)
motor disturbances were concomitant with epileptic seizures.
Males predominated
(50 male patients or 59.52%, versus 34
female patients or 40.47%)
.
In the first 6-8 months following the start of
the Center's activity, depending upon their age, patients were
administered 4-16 capsules of 500 mg of Glucaprim every day.
Aminovil was recommended at similar doses in the presence of a
hyperkinetic syndrome or seizures. With Glucaprim producing no
effect, the intake of Aminovil alone was recommended. Capsules
were administered twice daily.
As new amino acid preparations appeared, new
combinations acting on motor disorders emerged, for example,
Glucaprim + Primavit, Glucaprim + Aminovil +Primavit or
Glucaprim + Primavit + Vitamixt, the latter combination having
proved its merit in the presence of increased muscular tone of
mixed type with spastic and plastic component manifestations.
The subsequent observation of patients allowed
a new conclusion: as courses of treatment were repeated,
particularly, beginning with the third course in 42 patients,
the clinical effect was manifested at significantly smaller
dosages of amino acid preparations compared with the initial
periods of treatment. This was an indirect corroboration of
Prof. A.P. Khokhlov's hypothesis that an increased activity of
formerly inoperant nerve cells forms the basis for the recovery
of motor function in ICP patients.
If the course of
treatment was discontinued, the obtained effect did not
disappear but persisted during 3-4 months. To achieve a repeated
clinical result, minor amino acid dosages sufficed to stimulate
the functioning nerve cells. As a result, only 21 patients
(25%)
were asked to take the former dosages when they repeated courses
of treatment.
In another group of
patients (21
subjects = 25%),
repeated periods of treatment had to be conducted with
the use of diverse drug combinations. In this case, one half of
the patients of this group had to take amino acid combinations
for the purpose of further enhancing therapy effectiveness while
the other half received them because of the lacking effect. This
group was primarily made up of patients with severe hyperkinetic
and mixed forms of ICP. In treating these patients, it was
occasionally necessary to restrict the effect on isolated
disease symptoms, for instance, on a reduction of Spasticity
while hyperkinesias were retained.
Treating Adult Cerebral Palsy Patients
with Amino Acid Compounds
Amino acid compounds
have been used to treat adult patients with cerebral palsy. The
child's brain waves become adult-like 14-16 years, suggesting
that the brain has reached maturity by this age. Savin
suggests that the effectiveness of conventional rehabilitation
measures used to treat cerebral palsy
(ICP)
diminishes after age 14, since the brain is
no longer as plastic to change. In 1990, Prof. A.P. Khokhlov
suggested using amino acid preparations to provide therapy for
adult patients with cerebral palsy.
He examined and treated 55 patients with a
mean age of 24.1 years. Twenty-five patients were male and 28
were female. All subjects were cognitively intact; the majority
stressed that their condition had been stable for many years and
that conventional treatments had not produced any positive
effect.
Among the group of patients observed, 11
patients had spastic diplegia; 8 had hemipareses; 9 had
tetrapareses; 10 had hyperkinetic disease; and 14 patients had a
mixed form of hyperkinesias combined with pareses of the limbs.
Epileptic attacks were observed in 6 subjects. One female
patient had myclonias in muscles of the legs occurring over many
years. The course of treatment lasted 4-6 weeks.
To manage spastic forms
of the disorder, Glucaprim, Aminovil, Primavit, including their
combinations, were most often prescribed. To influence
hyperkinesias, depending on their type
(slow, rapid),
Trevit, Detrem, Aminocomposit, Vitamixt, Prima-F at individually
selected dosages and in combinations were given. Glucaprim and
Neoprim were administered to act on cerebellar disorders.
Subjective improvement was recorded in 52 out
of 53 patients within the first week of treatment. Among
objective symptoms, a manifest decrease in the muscular tone was
primarily recorded which concurrently combined with an increase
in the force and the volume of movements as well as with the
appearance of new movements. Such dynamics was registered in all
patients with spastic forms of the disease.
Diminished muscular tonicity and reduced
dystonic manifestations in patients with slow hyperkinesias,
along with an improvement of the subjective condition, enabled
these patients to execute more purposeful movements. At the same
time, patients reported a reduction of dysarthia; their mimics
became more lively. The concomitant prescription of Aminovil and
Aminocomposit turned out to be an effective combination that
affected tic hyperkinesias in the facial area. The degree of
manifestation of tics in 5 patients decreased in all.
Furthermore, all patients said they managed to more easily
suppress tics by volitional effort.
The efficacy of amino acid preparations was
less pronounced with regard to rapid hyperkinesias against the
background of low tonicity; hyperkinesias decreased after
treatment mainly in rest.
Improvement was recorded in respect to the
convulsive syndrome. In 4 out of 6 patients who suffered from
epileptic fits, a reduced occurrence of attacks was recorded. A
19-year old female patient, who for 12 years had been suffering
from daily multiple myoclonic fits in the legs that drastically
impaired her walking, improved. Aminovil treatment resulted in
total elimination of myoclonias that did not yield to any
preparations before.
Twenty-seven patients with pareses in the legs
but who could walk noted decreased fatigability in the legs; in
walking they could make a wider step, cover a larger distance;
their walking rate increased.
No substantial side effects of amino acid
drugs that would call for their withdrawal were recorded.
Twenty-three patients underwent repeated
courses of treatment. All of them stressed that between the
courses, the effect achieved after the previous course was
mainly retained which they had never noticed earlier when they
were treated conventionally.
Nevertheless, no randomized, controlled trials
have been conducted.
Over a two-year period, an
ophthalmologic examination of 723 patients with different
forms of infantile cerebral palsy
(ICP)
was carried out.
In 75
(10.4%) out of 723 ICP
patients who were treated with amino acids by Prof. A.P.
Khokhlov's method, Amauraosis
(blindness)
was recorded.
Amauraosis treatment results with amino acids
were analyzed in 32 patients. Favorable effects were recorded
1-2 weeks following the first course of amino acid treatment.
The child opened the eyelids, the "sleeping" child look
disappeared; the look became fixed if it was errant earlier.
Subsequently, the child's look became more conscious, the child
began to follow the parents, got interested in toys and picked
them up.
The look paresis decreased or disappeared
completely; the nature of nystagmus was altered: rotatory
nystagmus turned into large-swinging horizontal nystagmus; the
amplitude of oscillating movements and the volume of eyeballs
movement increased. The squint angle decreased from 5 to 20
degrees.
A reduction of the squint angle, the
disappearance of look paresis and a change of the nature of
nystagmus depend on the dosage, duration of the action of amino
acids and their combination.
Amino acid combinations
had the best effect on optical muscle disturbances
(Glucaprim, Aminovil,
Primavit or Primavit with Glucaprim or Aminovil alone).
Whereas "external"
Amauraosis manifestations
("sleeping" look, look paresis, etc.)
began to disappear 1-2 weeks after amino acids had been
prescribed, restoration did not occur before at least one course
of treatment.
The lids opened and the child's "sleeping
look" disappeared in 27 out of 32 patients with Amauraosis and
cerebral palsy as a result of amino acid treatment. Six patients
began watching light, 5 patient developed unstable and 12 stable
look fixation; in 4 subjects vision acuity was found to be from
0.01 to 0.08. Five patients reported no favorable effect.
Glucaprim combined with Aminovil and Neurovit seemed to
influence the optic nerve condition most beneficially.
Visual findings were classified into 3
groups:
- 1st group:
"negative effects" - absence of any positive optic
functions. The group included 5
(15.6%)
patients;
- 2nd group:
"satisfactory effects" - emergence of light perception in
conjunction with correct light localization and unstable
look fixation. Positive effects were identified in 11
(37.4%)
patients;
- 3rd group: "good
effects" - onset of stable look fixation, object vision
(the child
watches the parents, looks at toys, picks them up)
and restoration of vision acuity
from 0.01 to 0.08. Good results were recorded in 16
(15.0%)
out of 32 patients.
An improvement of the optic disks
condition in terms of color, sharpness of borders and
restoration of physiological excavation was found in 8
(25.0%)
patients. All 8 patients had Hydrocephaly and optic nerve
atrophy.
Besides, dependence of
treatment effects on dosage and time of drug intake was noted.
The best effect was produced when Glucaprim was administered at
full dosage (4
times daily) in the first
course of treatment.
In assessing the "good effects" group it was
found that in 16 patients stable look fixation was recorded in
12 subjects following the first course and in 4 after the second
course of treatment.
Acuity of vision from 0.01 to 0.04 was
reported in 3 patients once the 2nd course of treatment was
completed and in 1 patient after completion of the 3rd course.
No randomized clinical trial has been done.
