TIRTHY-SIX MONTHS OF DRUG THERAPY IN A CHILD

WITH LIGAMENTOUS LAXITY AND CLUMSINESS (updating May 2005)

 

Renato COCCHI, neurologist and medical psychologist They conclude that a child who demonstrates ligamentous laxity is more likely to sustain an extension supracondylar humerus fracture than a distal forearm fracture when he or she falls on the outstretched hand to break the force of the fall.

   Sigmundson and others, in 1998,  do the most updated revision of rehabilitative programs of the clumsiness, in use since 30 years.  In particular, the Perceptual Motor training, and the Sensory Integration Therapy have been heavily criticised, for their not maintained promises, or because they did not show more than a limited effect on perceptual-motor development as claimed.

  The more recently introduced kinaesthetic training is shown to have an effect on general motor competence. But this may be better explained in terms of the general principles on which this training procedure lies rather than the influence on Kinaesthesis per se.  Salman, 2002, recalls the role of the cerebellum in timing neural processes. The timing capabilities of the cerebellum appear to extend beyond motor control into tasks focusing on perceptual processing that require the precise representation of temporal information and sensorimotor learning. Its impairment would be able has some weight also in the clumsiness, although it cannot explain it as a whole.

  I did not find any information on a possible drug treatment. Since I started this in a boy who did not more benefit from rehabilitative therapies, first I want to give here a five-months report, which, I hope,  will be further updated.   

 

The case history.

 27.05.2002: male, seven years old at the first consultation. He suffers from ligamentous laxity and clumsiness mainly when running. Dysmetria is present and inaccurate fine motility. He had the diagnosis of a physiatrist as ligamentous laxity.  He is easily tired. Nighttime, he wear leg prostheses to improve the posture of his feet.  He has footwear with reverse peaks.  At school he goes better in arithmetic.
He has easiness to upper respiratory  tract infections. The mother has  modest ligamentous laxity.

 He is born following urgent Cesarean section, because maternal pelvic-fetal disproportion. His birthweight was 4020 grams. What is curious, he opened his eyes after a week, and there was eyes' blow up. In the first year of life he has given some feeding problems, and was oversleeping. He suffered from belly colics with the tendency to  constipation, not clear if it was atonic or spastic one. He started to catch frequents upper respiratory tract infections when he was three. Usually is a little pale, and when running he sweats  in an exaggerated way.  

Normally, he is enough serene and cheerful, but little self-complaining. He talks much. The parents are separated since about four years ago. Habitually he eats much, many sweet things, mainly chocolate. He tastes the meat broth, and  raw vegetable. He sleeps much, and he talks when sleeping, but he doesn't have drooling nor bruxism. In the morning he is more efficient, and in the afternoon needs rest. He bikes, but that tired him in a short time.

 Initial therapy, daily doses: Glutamine 250mg alternating with S-adenosil-l-methionine (SAMe) 200mg; pyridoxine 150mg; diazepam 0.8mg.  

 

01.07.2002: The child is little more tonic and less asthenic, but always a little uncoordinated. More control in his feeding, and eats little fewer sweet things. He is less complaining. He always need to have rest in the afternoon. The nighttime sleep improved. He doesn't speak more at night. He stretches more to the awakening. Not early-morning penis erection. His oversweating did not vary.

He talks very much. There are fewer differences between morning hours and the afternoon. His falling asleep goes well. No variations reported on his biking. His face is a little less pale.  

 21.10.2002: His clumsiness improved. On it there is a positive judgment of the physiatrist that followed it (see her certification transcribed below). The fine motility improved too. He doesn't  need to sleep more in the afternoon, because he says  to be not tired.  He mourns on must taking the drugs. He runs  more, but the bending of the knees is still reduced. Still bony scrunches to the shoulders, in abduction of the arms. He did not take the SAMe in regular way. Since he assumes it regularly,  the bony scrunches of the shoulders disappeared.

His face shows more colour, and sweats less. Penis erection appeared at morning. He tasted meat broth and chocolate. His health runs better, even if he does intense sporting activity at school.  His classmates accept him more. Bowel function is now regularized, while a little constipated in past. Now he is more slim. His sleeping is less heavy. Following his mother he improved at least 20%.
 

The Emilian physiatrist that followed him, has seen again him the last September and found him improved, so she has no more insisted with the need of a genetic investigation, to justify the stop in motor progresses of the boy. She was told that the boy practised intense physical activity during the summer, information already reported in the certificate written at the end of her checkup.  

She noted besides, in the same certificate: Ligamentous laxity. Internal torsion of the right shinbone = 10° and left = 15°. Plantar prostheses: general right foreversion = 50° and left = 68°. The dysmetria is not noticeable today. To the dorsal rachis light asymmetry L right convex  and left dorsal.
The boy needs to go on with: Long leg prostheses for the night; Footwear to swerve axle + one lateral 0.3 spur in the forefoot.  

Current therapy (daily doses): Creatine 1000mg; Oxazepam 7.5mg, Glutamine 250mg by alternating with SAMe 200mg. Pyridoxine 150mg.

 

28.04.2003: He is doing better. According to his the mother, from the beginning of the drug therapy to today he improved at least 50%. In mountains, he walked for 4km without any complain (before the drug therapy, after 500 metres he had to stop because tired). He has more endurance when biking and he enjoys it much more. Now he attends the swimming pool and swims by himself, without the life belts. The clumsiness is reduced.

His muscles are more tonic, for which he appears less "uncoordinated," as his mother said. He runs better. When he is going downstairs, he uses less the handrail support and now there is no difference between going upstairs and go downstairs. He jumps from two steps, as first, but now he doesn't fall more along the floor.

He doesn't succeed to run by overflexing the leg on the thigh and touching the gluteus with his heel, as his classmates do during the lesson of physical activity. The last consulted orthopaedic suspended every kind of support, by esteeming that they do not need anymore. Now, he is not wearing shoes with the reverse peaks. No more bony scrunches to the shoulders, in abduction of the arms..

As for his health he did well, but a pharyngitis with one antibiotic therapy in six months. He gained some body weight. There is no more greediness for the meat or cube broth, - now he likes the pasta - and even no more greediness for the chocolate. The quantity of food of his diet is under his control, he eats more raw vegetables. When among other children he inclines to become a little hyperactive ( a compensation symptom for his previous sending off due to his clumsiness?)

His attention increased and at school he is going better with increased notes both in Italian and in arithmetic. He has the habit of refusing to do little help in his house ( eg. He says that he does not want to clear the table ) but then, when alone, he does what asked him. He does want the others see that he obeys at once to the orders. Regular bowel function, regular sleep, his awakenings are well.

The fingernails grow stronger, while first they were weak with easiness to broken. He sweats lesser. Some time puffs for the taking the pills, but he is perfectly sentient of their utility. He speaks more and stands better erect.

Current therapy (daily doses): Creatine 2g; Oxazepam 7.5mg, Glutamine 250mg by alternating with SAMe 200mg. Pyridoxine 150mg.

 

27 October 2003: He is doing better, but he shows till some awkwardness in the running. He shows even clumsy running in the last part of the road that he crosses on foot, when going to school. His feet always little face towards the internal side. Increased the endurance, but he is biking only a few, even because the parents not leave it going out the courtyard of his house. He does swim, but he does not finish the long side of the swimming pool, so he does not go from a head to the other. Now, he jumps from three stair steps. Like his classmates do during gymnastics lessons, he succeeds to run by overflexing the leg on air on his thigh, touching the gluteus with his calcaneum. Not more scapular noise, which reappeared when the mother stopped the SAMe, and disappeared again after its resumption. In the afternoon he does not go more to sleep, as he did to recover energy. The relatives observed his improvement. No more long leg prostheses for the night in use, and the shoes are without plantar prostheses.

As for his health, he had some cough since he started the school. Corticosteroids for five days were prescribed. The last summer he suffered from colitis for about two months.

Towards 7 PM he has to eat, if not he does it, he has colic ache. His mother says that he improved 55%, he increased in its strength and in his tallness but not in weight. Less oversweating now, which in past appeared five minutes after physical activity, and now only after half an hour. At school he is doing well. The classmates do not take him more in turn. He is no more isolate in the interval between the lessons. He speaks very much, and stands more erected. Sometimes he mourns about his drug taking.

Therapeutic variation: Pyridoxine 75mg.

 

26.04.2004: As for clumsiness, there are only fewer improvements. He is clumsy in running and in walking. His running is slow. Touching the gluteus muscle with the heel is always a hard task. During the winter he did poor physical activity. When he is going up and downstairs, he does not need to hold more the handrail. Now he jumps down from 2-3 steps of the stairs. He has more strength and more endurance. Since the classmates say him as clumsy, he takes offence at it. He does not wear anymore leg prostheses at night.

Oversweating did not vary, and the boy sweats after 20-30 minutes of animate game, but perhaps, for the sweat, it is lesser. He is afraid of anything (ants, flies, spiders, and, too being at home, of the storm). The teachers said that he had poor self-esteem. When they question him while they are explaining, he turns red and extends to jam. Usually, he inclines to do less of what he may do.

He is speaking always much, he has his face more pink, his weigh is 35kg and his height is 129cm. Now he has a reduced sense of hunger and he has not more feeling of "a hole" in his stomach. Now he controls more his appetite even in presence of the preferred foods and so he lowered of one kilogram.

Last winter he suffered from coughs and tonsillitis and he had to take antibiotics. His mother did not see any penis erection. When relaxed, there is a kind of scratching on his genitals. He had a period of agitation, and he was biting his nails as well as the short skin around to the fingernails.

Therapeutic variation (daily doses, by the oral via ): The s-adenosyl-l-methionine stopped. It is prescribed chlomipramine 10mg.

08 November 2004, The sixth checkup under drug therapy, always maintained. He is doing better, even if not in all his motor skills. His endurance became greater. Every week he plays two basketball hours + another hour at school. Sweating appears a few more than his classmates. Then, he feels tired till evening. He has a less ready sprint, in comparison with the others, and this even in running, during the hour of physical education. Now he is much biking. In plain he withstands an hour and half biking. He climbs and goes down the stairs without the handrail. When he jumps from the second step, he never falls, while some time he falls when he jumps from the third step.

The school results were well gone and now he attends the fourth year of elementary school. At home, as for the study, he does not always put a lot.

There is no information on the judgment by the teachers after the summer holidays.

Altogether improved, he has more desire to do, he is more resistant, plays of more, more happy, more integrated in the peers' group. He has done a survival camp, without fear. He does crack the articulations of the hands' fingers. Now, he speaks better and is more confiding with his mother.

He has reduced his moving aside less and he is more aggressive against the little sister, who was taking advantage. He defends himself of more. Some times he seems return to be timid.

His health did not go well. He had cough and tonsillitis every 15 days, for which he was given many antibiotics. Now he is periodically taking a vaccine, which seems it is protecting him. At night he does not speak more during the sleep and not has any nighttime bruxism. The sleep is lighter and inclines to throw off his clothes.

Eating is regulated, and he became taller (130.5 cm) but not more weigh. Usually he eats more vegetable, when forced, and fruit. His greediness for sweet things changed very few.

In summer he was taking a tablet of 10mg chlomipramine every day, while now he takes one every two days, because he had a quite exciting period. At the beginning of the new school year, he suffered from a panic attack [?] for which he took again 10mg chlomipramine daily, for 15 days.

Therapeutic variation (daily doses, by the oral via): 5-hydroxytriptophan, 25mg.

 

 

End May 2005, the seventh checkup. In this period he did quite well, even as for his health, with an only tonsillitis. Following a telephone agreement, his mother stopped the chlomipramine, because it made him a little stunned. He is still slow, but stamina is going better. He improved the relationship with the peer group. Now, he attends a basket preparatory course, with three training every week [??]. Some time, during running, he succeeds to touch the gluteal muscle with his heel. At school he has more than discreet results. While first his smaller sister dominated him, now he imposes to her.

His self-esteem is growing. When he wakes up the presence of an early-morning erection of the penis is increased. He sleeps well, and his sleep is less heavy. To his mother, I explain that, of fact, the child is doing a substituting therapy, but I do not know if he will always take it. Perhaps his body, at the end, will find an efficient balance, and so he will stop the drugs taking.

No therapy variation.

Discussion.

 In spite of a  possible hereditary component, two were however the aspects that drove me to try a drug therapy: The stress symptom present and a personal experience with the use of the SAMe in the ligamentous laxity in Down children.
 I considered stress symptoms, defective or of compensation (Cocchi, 1985):

- the asthenia;

- a tendency to the hypersomnia;

- the need to rest in the afternoon;

- the easiness to upper respiratory tract infections;

- the overeating; - the greediness for sweet things, mainly the chocolate; - the oversweating; - the pallor.  

Either the need of sweet things and the taste of the meat broth pointed out on a reduction of GABAergic pathways, with reduced type A GABAergic inhibition (Cocchi, 1987).   

 On such neurochemical circuits I acted with glutamine (A precursor of the glutamic acid and the GABA), pyridoxine  (The catalyst of the GAD, as the cofactor of the transformation of the glutamic acid into GABA ) and diazepam (as a benzodiazepine, one sensitizer of the type A GABAergic receptor).  

As for the SAMe, in the preliminary communication on its effect on the ligamentous laxity in the Down child (Cocchi, 1990) it seemed me that such action could be justified from these reasons, which follow.
 "Since homocysteine comes out from the SAMe, the prescription of SAMe could then drive, among other results, to a larger availability of homocysteine. Consequently it could drive to an increased activity of growing bones cartilages, in the years when the body grows.
 By this way we could reach a reduced imbalance between articular tissues and articular bones size, so decreasing the ligamentous laxity.

 This one is a suggestion not too ease to verify, even because many variables coexist.  First, there is the fact that I add the SAMe [in Down children] to the previous regimen in a second time, having started the treatment with antistress drugs.  Second, the prescription of the SAMe as the sole drug seems to have contradictory effects on psycho-endocrine responses to stress (Stramentinoli, 1987b). So it could be difficult to use it as monotherapy in Down persons.   

Finally, I cannot affirm that improved ligamentous laxity has a necessary link with the SAMe. Nevertheless, I noted this result on children with ligamentous laxity only after I added the SAMe to the regimen."  

In this non-Down child, but with ligamentous laxity, this previously hypothesized effect was willingly looked for,  and it was already observed  at the first checkup after a month of drug therapy.

 On other hand, after thirty months, also nearly all the stress symptoms are at least attenuated.
 Both more evident symptoms, in this child, the ligamentous laxity and the clumsiness benefitted from the drug therapy prescribed (the effect of the creatine does not have still a checkup). That happened when the phyisiatric intervention, as surely appropriate and with his efficacy, did not seem may  bring other improvements.  

Eventually, I personally have doubts that the cerebellar involvement, which  surely exists for the presence of the dysmetria symptom, may be faced with the physiatric therapy alone.  
Moreover, the increasing of the physical activity, in a peripheral asthenic subject, would have even worsened the asthenia itself for the consequent physical tiredness. We need to remember, as for it, that the boy had to go to rest in the afternoon, to recover his strengths.

 This would be a self-perpetuating circle that could be only interrupted by giving energy to the muscles. The glutamine assumption, which the organism produces mainly from the muscular ATP, save up this last one.

 The creatine is a precursor of the ATP that allows to improve the physical endurance, and its addition to the regimen has just brought to results otherwise obtainable in a short time like that.

There is a new fact, concerning the SAMe. The scapular noise, which was missing, reappeared after the suspension of the SAMe his mother decided. It then disappeared again to drug resumption. The A-B-A sequence, missing-reappearing-missing again, in the same case, as related to the assumption of the SAME, confirms the action of this drug on the joints.

The last checkup revealed some symptoms of depression, although the boy was apparently serene.

Thirty-six months later, as for the motility, it is not clear if he is doing a substituting therapy, or even curative one. The cracking of the articulations of the hands' fingers is surely a sign of decreasing of the joint laxity.

  

Conclusions.   

In a child with ligamentous laxity and clumsiness an antistress drug therapy, able also to the saving of the ATP and to possible improve the ligamentous matter,  has brought to an amelioration in both basic symptoms of base, after 36 months. This clearly opens many questions to which I should try to answer in the following updating of the case.

 

References.

Agnew P.:  Evaluation of the child with ligamentous laxity. Clin Podiatr Med Surg 1997, 14:117-130.

Cocchi R.: A syndrome from possible GABA deficiency. Clinical therapeutic report of 15 cases. Acta Pschiat. Belg. 78, 407-424, 1978.

Cocchi R.: Le depressioni infantili. In: Strutture e dinamiche psicopatologiche in età evolutiva. Montefeltro, Urbino 1985: 163-183.

Cocchi R.:  Hypo-A-GABA-erge  Depression  bei Kindern. Klinisches  Bild und mit neurochemischen Mechanismen verbundene Symptome. In Friese H.-J., Trott G.-E. (eds): Depression in Kindheit und Jugend. Huber, Bern 1988: 126-133.

Cocchi R.: La S-Adenosil-L-Metionina (SAMe) riduce la lassità articolare nel bambino Down? (Comunicazione preliminare). Riv.Disturbo Intellet. 1990, 3: 141-144.

Nork SE; Hennrikus WL; Loncarich DP; Gillingham BL; Lapinsky AS. Relationship between ligamentous laxity and the site of upper extremity fractures in children: extension supracondylar fracture versus distal forearm fracture. J Pediatr Orthop B 1999, 8:90-92.

Salman M.: The cerebellum: it's about time! But timing is not everything-new insights into the role of the cerebellum in timing motor and cognitive tasks. J Child Neurol 2002, 17: 1-9.

Sigmundsson H; Pedersen AV; Whiting HT; Ingvaldsen RP. We can cure your child's clumsiness! A review of interven-tion methods. Scand J Rehabil Med 1998 Jun;30(2):101-106.

Stramentinoli G.: Neuroendocrine effects of S-adenosylmethionine (SAMe)  (dattiloscrit-to). BioResearch, Milano 1987b.  

 

Posted in Internet on November 2002. Copyright by Renato Cocchi, 2002

Author's address: dr. Renato COCCHI, via Rabbeno, 3

42100 Reggio Emilia (Italy)

renatococchi@libero.it

 

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