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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.1
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 1996.2
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 hyperkineses 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 + Primavi t + 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 hyperkineses were retained.
[Return to "Quick-Index" of Amino Acid Therapy for Cerebral Palsy]
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. Savin3 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 hyperkineses 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 hyperkineses, 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 hyperkineses, 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 dysarthria; 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 hyperkineses against the background of low tonicity; hyperkineses 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.
[Return to "Quick-Index" of Amino Acid Therapy for Cerebral Palsy]
Over a two-year period, an ophthalmologic examination of 723 patients with different forms of infantile cerebral palsy (ICP) was carried out.4 In 75 (10.4%) out of 723 ICP patients who were treated with amino acids by Prof. A.P. Khokhlov's method, amaurosis (blindness) was recorded.Amaurosis 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" amaurosis 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 amaurosis 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:
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.
- 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.
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.
[Return to "Quick-Index" of Amino Acid Therapy for Cerebral Palsy]
[Return to "Quick-Index" of Amino Acid Therapy for Cerebral Palsy]
Program Director, Continuum Center for Health and Healing,
Beth Israel Hospital / Albert Einstein School of Medicine
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