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NEW THERAPIES FOR RETT SYNDROME

  • May 2019
Authors:
Aamir Al Mosawi at Children Teachig Hospital, Baghdad Medical City
Aamir Al Mosawi
  • Children Teachig Hospital, Baghdad Medical City
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Abstract and Figures

There is no satisfactory therapy for Rett syndrome, a rare genetic disorder. A three-year old girl with Rett syndrome was hypotonic, ataxic, and had abnormal movements of the upper limbs. She was unable to sit alone on a chair and showed no eye contact and was not responding to her name. She didn't have purposeful hand movement and was not able to hold things. She couldn't be held erect in the standing position. She was not saying any word nor was babbling. The girl received two treatment courses. The first course included intramuscular cerebrolysin 1ml daily for ten days. The second course included 10 cerebrolysin injections, 3ml every third day, and oral citicoline. After the ten-day course of cerebrolysin, she showed dramatic improvement in muscle tone and was able to sit on a chair, and she had no abnormal movements. It was also possible to hold her straight in the standing position without apparent ataxia. After the second course of treatment she showed marked improvement with the development of purposeful movement and the ability to hold feeding bottle with assistant of the mother and feed herself. She was able to stand and step one step holding furniture. She started babbling and showed some reduction in the autistic features. The use of these new therapies in Rett syndrome resulted in an obvious improvement that has never been reported before.
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2019 May Edition |www.jbino.com | Innovative Association
J.Bio.Innov 8(3), pp: 301-307, 2019 |ISSN 2277-8330 (Electronic)
Mosawi et al.,
NEW THERAPIES FOR RETT SYNDROME
Aamir Jalal Al Mosawi
Children Teaching Hospital,Baghdad Medical City,Bab Al Muadham,Baghdad, Iraq
ABSTRACT
There is no satisfactory therapy for Rett syndrome, a rare genetic disorder. A three-year old
girl with Rett syndrome was hypotonic, ataxic, and had abnormal movements of the upper
limbs. She was unable to sit alone on a chair and showed no eye contact and was not
responding to her name. She didn’t have purposeful hand movement and was not able to
hold things. She couldn’t be held erect in the standing position. She was not saying any word
nor was babbling. The girl received two treatment courses. The first course included
intramuscular cerebrolysin 1ml daily for ten days. The second course included 10 cerebrolysin
injections, 3ml every third day, and oral citicoline. After the ten-day course of cerebrolysin,
she showed dramatic improvement in muscle tone and was able to sit on a chair, and she
had no abnormal movements. It was also possible to hold her straight in the standing position
without apparent ataxia. After the second course of treatment she showed marked
improvement with the development of purposeful movement and the ability to hold feeding
bottle with assistant of the mother and feed herself. She was able to stand and step one
step holding furniture. She started babbling and showed some reduction in the autistic
features. The use of these new therapies in Rett syndrome resulted in an obvious
improvement that has never been reported before.
Key words: Rett syndrome, cerebrolysin, citicoline.
No: of Figures : 03 No: of
References:12
2019 May Edition |www.jbino.com | Innovative Association
J.Bio.Innov 8(3), pp: 301-307, 2019 |ISSN 2277-8330 (Electronic)
Mosawi et al.,
INTRODUCTION
Rett syndrome is a rare X-linked dominant
genetic disorder affecting only girls. The
disorder is generally regarded as a
neurodevelopmental condition rather than
a neurodegenerative disorder. The
diagnosis is generally based on clinical
findings which characteristically include
(Galli et al.,1985; Peters, 1985):Delayed
motor development and delayed speech
development.Ataxia or fine tremor of hand
movements.Repetitive hand-wringing
movements and loss of purposeful and
spontaneous use of the hands. Autistic
feature is a typical finding in all patients.
Generalized tonic-clonic convulsions occur
in the majority and are usually well
controlled by anticonvulsants.
Many patients also develop respiratory
abnormalities with intermittent periods of
apnea that may be associated with
cyanosis.Feeding problems and poor
weight gain are common. Rett syndrome
was most probably first described in
German language in 1966 by Andreas Rett,
a pediatrician in Vienna (Rett,1966) .
Bengt Hagberg, a Swedish pediatrician,
published an English article in 1983 and
named the condition after Rett (Hagberg et
al.,1983).More than half century after the
syndrome was first described, and there is
no known effective therapy that can
improve Rett syndrome, and treatment
mostly includes anticonvulsants to control
seizures.
Patients and methods
A girl with Rett syndrome was first seen at
the age of about three years because of
developmental delay, abnormal
movements, and autistic features. The girl
had history of convulsions and was taking
sodium valproate. She also had poor
feeding and respiratory abnormalities with
intermittent periods of apnea associated
with cyanosis.The girl was not able to sit
alone on the chair and showed no eye
contact and was not responding to her
name (Fig.1).
She didn’t have purposeful hand
movement and was not able to hold things.
She was hypotonic and ataxic, and had
abnormal movements of the upper
limbs.She couldn’t be held erect in the
standing movement, and she was not
saying any word nor was babbling.
Audiogram showed normal hearing. Brain
MRI showed mild ventriculomegaly.
The girl was initially treated with cerebrolysin
1ml daily given by intramuscular injections
for ten days.A second course of treatment
given over one month included:
Cerebrolysin 3ml given by intramuscular
injections every third day, received ten
doses.Oral citicoline 2ml (200mg) daily.The
protocol for this research was approved by
the scientific committee of Iraq
headquarter of Copernicus Scientists
International Panel and conforms to the
provisions laid out in the Declaration of
Helsinki (as revised in Edinburgh 2000).
Results and Discussion
After the ten-day course of cerebrolysin, the
girl showed dramatic improvement in
muscle tone and was able to sit on a chair
(Fig. 2), and she had no abnormal
movements or apparent ataxia. It was also
possible to hold her straight in the standing
position.After the second course of
treatment she showed marked
improvement:She developed purposeful
2019 May Edition |www.jbino.com | Innovative Association
J.Bio.Innov 8(3), pp: 301-307, 2019 |ISSN 2277-8330 (Electronic)
Mosawi et al.,
movements and was able to hold feeding
bottle with the assistant of her mother and
fed herself (Fig. 3).
She was able to stand and step one step
holding furniture (Fig. 3).She started
babbling.She showed some reduction in
the autistic features according to the
mother, but at the clinic she remained not
responding to her name and didn’t show
obvious eye contact.There is no specific nor
satisfactory therapy for many of the
disabling neurological disorders such as Rett
syndrome.
Cerebrolysin solution which can be given
intramuscularly consists of low-molecular-
weight neuro-peptides including nerve
growth factor, glial cell line-derived
neurotrophic factor, brain-derived
neurotrophic factor, and ciliary
neurotrophic factor.Cerebrolysin solution is
a safe, well-tolerated, and efficacious
neuroreparative agent that is associated
with a relatively wide therapeutic time
window (Al Mosawi , 2017).
Previous reports of the use of cerebrolysin in
patients with Rett syndrome suggested that
it can improve behavior, attention level,
motor functions, and nonverbal social
communication.
The EEG parameters of the patients with
Rett syndrome could also be normalized
with the use of cerebrolysin
(Gorbachevskaya et al.,2001).The use of
cerebrolysin in childhood autism and autism
spectrum disorder was also associated with
a beneficial.Krasnoperova et al., (2003)
reported the use of cerebrolysin in the
treatment of nineteen children with
childhood autism and eight with Asperger's
syndrome. Treatment with cerebrolysin was
associated with improvement of cognitive
functions (expressive and receptive
speech, fine motoring, playing). Positive
effects were noted in all the patients with
Asperger's syndrome and in 89% of the
patients with childhood autism.
Treatment was not associated with any side
effect (Krasnoperova et al., 2003).Radzivil
and Bashina (2006) described an open
prospective clinical study of the use of
cerebrolysin with a beneficial effect in the
treatment of twenty five patients with
childhood autism.Chutko et al (2017)
reported that the use of cerebrolysin in the
treatment of forty three children with autism
spectrum disorders was associated with
improvement observed in 27 patients
(62.8%).
Cerebrolysin can improve brain functions
through (Al Mosawi , 2017) :Inhibition of
apoptosis.Stimulation of neurogenesis
through stimulating proliferation,
differentiation, and migration of adult
subventricular zone neural progenitor stem
cells.Stimulation of stem-cell proliferation in
the brain.Citicoline (cytidine diphosphate-
choline) or cytidine 5 diphosphocholine is a
nootropic agent with a very low toxicity and
has been approved for treatment of head
trauma, stroke, and neurodegenerative
disease in Japan and Europe (Al Mosawi ,
2017).As a safe neuro-protective agent,
citicoline may improve brain functions
through the following mechanisms (Al
Mosawi , 2017):
Preservation of cardiolipin and
sphingomyelin Preservation of arachidonic
acid content of phosphatidylcholine and
phosphatidylethanolamine.Partial
restoration of phosphatidylcholine
levels.Stimulation of glutathione synthesis
and glutathione reductase
activity.Reduction of phospholipase A2
activity.Increasing glucose metabolism in
the brain.Increasing cerebral blood
2019 May Edition |www.jbino.com | Innovative Association
J.Bio.Innov 8(3), pp: 301-307, 2019 |ISSN 2277-8330 (Electronic)
Mosawi et al.,
flow.Reducing oxidative stress and
preventing excessive inflammatory
response in the brain by inhibiting the
release of free fatty acids and reducing
blood brain barrier breakdown.
Fig.1: A three-year old girl with Rett syndrome. The girl was not able to sit alone on
a chair and showed no eye contact and was not responding to her name.
Fig. 2: After the first course of cerebrolysin, the girl showed dramatic improvement
in muscle tone and was able to sit on a chair
2019 May Edition |www.jbino.com | Innovative Association
J.Bio.Innov 8(3), pp: 301-307, 2019 |ISSN 2277-8330 (Electronic)
Mosawi et al.,
Fig. 3: After the second course of treatment, the girl was able to hold feeding bottle
with the assistant of her mother and fed herself. She was able to stand and step one
step holding furniture
2019 May Edition |www.jbino.com | Innovative Association
J.Bio.Innov 8(3), pp: 301-307, 2019 |ISSN 2277-8330 (Electronic)
Mosawi et al.,
Enhancing cellular communication by
increasing the availability of
neurotransmitters, including acetylcholine,
norepinephrine, and dopamine.Lowering
increased glutamate concentrations and
increasing the decreased ATP
concentrations induced by
ischemia.Increases dopamine receptor
densities. Al Mosawi (2019) reported a
retrospective observational study
describing the use of cerebrolysin and
citicoline for the treatment of eight of 19
patients with autism and Asperger
syndrome. Seven patients had autism and
one patient had Asperger syndrome.
All the treated patients showed
improvement and marked lessening of the
autistic features with six patients showed
complete disappearance of the main
autistic features. No patient developed any
side effects. The eleven patients observed
during the same year who didn’t receive
this treatment or were treated with other
treatments such as omega-3 and
risperidone didn’t show any lessening effect
in the autistic features. However, one
patient was treated with citicoline injection
showed obvious improvement in the autistic
features. In this study, the use of
cerebrolysin and oral citicoline in the
treatment of Rett syndrome resulted in an
obvious improvement that has never been
reported before.
References
Galli V, Ciccarone V, Venuta A, Ferrari P,
Cavazzuti GB. Rett syndrome. Review of the
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Peters AC.The Rett syndrome. Tijdschr
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PMID:4095698 [Article in Dutch].
Rett A. On a unusual brain atrophy
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childhood. Wien Med Wochenschr 1966
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Al Mosawi AJ. A novel therapeutic
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Gorbachevskaya N, Bashina V, Gratchev V,
Iznak A. Cerebrolysin therapy in Rett
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Brain Dev 2001; 23 Suppl 1:S90-S93.
Krasnoperova MG, Bashina VM, Skvortsov
IA, Simashkova NV. The effect of
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Radzivil MG, Bashina VM. An effect of long-
term cerebrolysin therapy in
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endogenous childhood autism]. Zh Nevrol
Psikhiatr Im S S Korsakova 2006; 106(2):21-5.
PMID: 16548370[Article in Russian].
2019 May Edition |www.jbino.com | Innovative Association
J.Bio.Innov 8(3), pp: 301-307, 2019 |ISSN 2277-8330 (Electronic)
Mosawi et al.,
Chutko LS, Yakovenko EA, Surushkina SY,
Kryukova EM, Palaieva SV. The efficacy of
cerebrolysin in the treatment of autism
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Korsakova 2017; 117(9):71-75. PMID:
29053124 [Article in Russian].
Al Mosawi AJ. The use of cerebrolysin and
citicoline in autism and Asperger syndrome.
J Bio Innov 2019; 8(1), pp: 99-108.
... Rett Disorder: It was most probably first described in German language in 1966 by Andreas Rett (Figure-6), a pediatrician in Vienna. Bengt Hagberg, a Swedish pediatrician, published an English article in 1983 and named the condition after Rett [5,6]. ...
... Within several months, the boy reached a state of overtly bizarre behavior and dementia, and was saying nothing. At the clinic, the boy showed marked repetitive movements, and was rather uncontrollable and tried to move from place to place in the room A three-year girl had Rett syndrome and her case and early treatment was published [5]. ...
... She was able to stand and step one step holding furniture. She started babbling and showed some reduction in the autistic features [5]. ...
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  • Dec 2019
Background: Pervasive developmental disorders include five chronic disorders marked by early impairment in socialization, communication and behavior. Little is known about the types of pervasive developmental disorders in Iraq. This is a retrospective clinical study aiming at determining the types of pervasive developmental disorders in Iraqi children observed at the pediatric psychiatry clinic in a tertiary pediatric referral center. Patients and methods: During nine months period (November 18th, 2018 to July 18th, 2019), fifty one patients with a diagnosis of pervasive developmental disorders (30 males and 21 females) were observed at the psychiatry clinic at the Children Teaching Hospital of Baghdad Medical City. Their ages ranged from two and half years to twelve years. Results: Thirty two (17 males and 15 females) patients had autism without significant mental retardation as indicated by adequate urine and bowel control and self care skills particularly spoon feeding. Thirteen patients were considered to have atypical autism or Pervasive developmental disorder not otherwise specified (10 boys and 3 girls), in eleven of them, the disorder was considered atypical because of the lack of adequate urine and bowel control and self care skills particularly appropriate spoon feeding indicating significant degree of mental retardation. In one patient, his condition was considered a typical because of the presence of an acceptable eye contact and response appropriately to name in most instances. Three patients had Asperger syndrome including two girls and one boy. Two boys had childhood disintegrative disorder (Heller syndrome), one of them have changes on brain MRI suggestive of cerebral vasculitis. One girl had Rett syndrome and her case and early treatment was published. Conclusion: In this series, typical autism without significant mental retardation accounted for 63%. Atypical autism (Pervasive developmental disorder not otherwise) was the second most common type of Pervasive developmental disorders accounting for about 25%. Asperger syndrome accounted for only 6% of the cases in this series
... However, patients with Asperger syndrome have good speech development. A child with acceptable eye contact and acceptable response to name can not receive the diagnosis of an autism disorder [1][2][3][4][5][6][7][8][9][10]. ...
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Background: We have previously reported our extensive experiences with autism disorders and their treatments, and we showed the possibility of curing the major autistic features with a new therapeutic approach which included individualized courses of intramuscular cerebrolysin as the main therapy for the main autistic features. Our previously published experiences included observing the occurrence of atypical autism associated with evidence of mental retardation in four brothers from outside Baghdad, each two of them from two unrelated families. The four patients were treated based on our extensive published experiences with the pharmacological treatments of autism disorders; however, the follow-up and the outcome of treatments of these four children were not described in the previous publications. The aim of this paper is to report the cure of the major autistic features in 2 brothers with autosomal recessive autism. Patients and methods: It was possible to follow the first two brothers for only few weeks and to see them after the first course of treatment, however, the second brothers were followed for more than one year, and it was possible to achieve cure of the main autistic features. Results: After one short course, the first two brothers showed slight but noticeable improvement. The younger brother showed some reduction in autistic features as he developed rather an acceptable eye contact. However, the two brothers were still not responding to name and didn’t say any word. After, treatment, the second two brothers showed no autistic features, and experienced significant improvements in speech and cognitive functions. The older brother was not having autistic features after eighth months, and was obeying commands, but was still saying only few words. The younger brother joined primary school and was doing well apart from some behavioral problems especially running away from school and sometimes breaks things. Conclusion: In this paper, cure of autism has been achieved in two boys with autosomal recessive disorder. However, cure of autism in older children has never been expected to totally normalizes them, as the patients have already lost several years of learning, social adaptation, and maturation of personality and behavior.
... However, patients with Asperger syndrome have good speech development. A child with acceptable eye contact and acceptable response to name can not receive the diagnosis of an autism disorder [1][2][3][4][5][6][7][8][9][10]. ...
Autosomal Recessive Autism: Cure of the Major Autistic Features
Article
Full-text available
  • Sep 2021
Background: We have previously reported our extensive experiences with autism disorders and their treatments, and we showed the possibility of curing the major autistic features with a new therapeutic approach which included individualized courses of intramuscular cerebrolysin as the main therapy for the main autistic features. Our previously published experiences included observing the occurrence of atypical autism associated with evidence of mental retardation in four brothers from outside Baghdad, each two of them from two unrelated families. The four patients were treated based on our extensive published experiences with the pharmacological treatments of autism disorders; however, the follow-up and the outcome of treatments of these four children were not described in the previous publications. The aim of this paper is to report the cure of the major autistic features in 2 brothers with autosomal recessive autism. Patients and methods: It was possible to follow the first two brothers for only few weeks and to see them after the first course of treatment, however, the second brothers were followed for more than one year, and it was possible to achieve cure of the main autistic features. Results: After one short course, the first two brothers showed slight but noticeable improvement. The younger brother showed some reduction in autistic features as he developed rather an acceptable eye contact. However, the two brothers were still not responding to name and didn't say any word. After, treatment, the second two brothers showed no autistic features, and experienced significant improvements in speech and cognitive functions. The older brother was not having autistic features after eighth months, and was obeying commands, but was still saying only few words. The younger brother joined primary school and was doing well apart from some behavioral problems especially running away from school and sometimes breaks things. Conclusion: In this paper, cure of autism has been achieved in two boys with autosomal recessive disorder. However, cure of autism in older children has never been expected to totally normalizes them, as the patients have already lost several years of learning, social adaptation, and maturation of personality and behavior.
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Full-text available
  • Sep 2021
Researchgate est devenu l'outil le plus important pour l'évaluation de la stature académique, des prouesses et de la productivité des médecins, ainsi que pour l'évaluation du leadership académique. Plus de 200 profils Researchgate ont été examinés au cours des quatre derniers jours d'août 2021 dans le but de déterminer les leaders médicaux académiques irakiens qui ont un score de réputation scientifique (RG) chez Researchgate de 40 ou plus. Aamir Jalal Al-Mosawi est le médecin universitaire irakien qui a obtenu le score RG le plus élevé, soit 40,46. Les résultats de cette étude confirment que Researchgate est plus approprié pour le leadership médical universitaire car il réduit dans une certaine mesure l'influence d'un indice H élevé et trompeur qui n'est pas pertinent pour la détérioration du leadership universitaire résultant de la participation à un grand nombre d'études collaboratives.
THE USE OF CEREBROLYSIN AND CITICOLINE IN AUTISM AND ASPERGER SYNDROME
Article
Full-text available
  • Jan 2019
There is no known curative therapy for pervasive developmental disorders (PDD) which include autism, Asperger syndrome, and atypical autism. Marked improvement or disappearance of autistic features in these disorders has not been reported with any therapy before.The aim of this paper is report a retrospective observational study describing the use of a new therapeutic approach for the treatment of eight of 19 patients with PDD. The treated patients ages ranged from 3 to 16 years. The new therapeutic approach which included injectable cerebrolysin as the main therapeutic component. The patients ages ranged from 3 to 8 years. Seven patients had a diagnosis of autism and one patient had a diagnosis of Asperger syndrome. Treatment aimed at improving the cardinal feature of PDD which is the impairment of social interaction which is mostly manifested by poor responsiveness to their name and infrequent engagement with others manifested by poor eye contact and infrequently looking to faces. All the treated showed improvement and marked lessening of the autistic features with six patients showed complete disappearance of the main autistic features. No patient developed any side effects. The eleven patients observed during the same year who didn't receive this treatment or were treated with other treatments such as omega-3 and risperidone didn't show any lessening effect in the autistic features. However, one patient was treated with citicoline injection showed obvious improvement in the autistic features.
The efficacy of cerebrolysin in the treatment of autism spectrum disorders
Article
Aim: To evaluate clinical and neurophysiological changes in children with different variants of autism spectrum disorders during treatment with cerebrolysin. Material and methods: Forty-three children with autism spectrum disorders, aged 4-6 years, were included in the study. To assess the degree of autism, the quantitative scale of assessing the severity of child autism CARS ('Childhood Autism Rating Scale') was used. A comparative analysis of the clinical picture of disease and data of the electroencephalographic examination in endogenous and exogenous (organic) variant of autism was made. Results and conclusion: In children with exogenous (organic) autism, the lower scores of autistic symptom on the CARS and a greater degree of functional immaturity of the cerebral cortex, according to electroencephalographic results, were found compared to children with endogenous autism. After treatment with cerebrolysin, 27 children (62.8%) showed signs of improvement. An improvement was noted in 13 children in with endogenous autism (56.5%) and in 14 children with organic autism (70.0%). CARS scores showed a more pronounced decrease in this indicator in a subgroup of children with organic autism.
[Rett syndrome. Review of the literature and presentation of 2 clinical cases]
Article
In this paper we report the cases of two girls affected by a progressive encephalopathy. Both stories are similar. After a normal development in the first year of life, neurological regression occurred since the beginning of the second year. This progressive syndrome led within a few months to a loss of any verbal acquisition, loss of purposeful use of the hands, dementia, autism. Other neurological alterations occurred in the following years: piramidal signs at lower limbs, generalized and partial seizures, ataxia, gait apraxia. All laboratory findings were normal in both girls. The EEG was abnormal in both patients and the patterns were quite the same in following records of both girls. The disease occurred in our patients is quite certainly the same described by Rett for the first time in 1966.
The efficacy of cerebrolysin in the treatment of autism spectrum disorders
  • Jan 2017
  • 301-307
  • A Rett
  • Mosawi
Rett A. On a unusual brain atrophy J.Bio.Innov 8(3), pp: 301-307, 2019 |ISSN 2277-8330 (Electronic) Mosawi et al., Chutko LS, Yakovenko EA, Surushkina SY, Kryukova EM, Palaieva SV. The efficacy of cerebrolysin in the treatment of autism spectrum disorders. Zh Nevrol Psikhiatr Im S S Korsakova 2017; 117(9):71-75. PMID: 29053124 [Article in Russian].
On a unusual brain atrophy
  • A Rett
Rett A. On a unusual brain atrophy
  • Jan 2019
  • 301-307
  • Mosawi
J.Bio.Innov 8(3), pp: 301-307, 2019 |ISSN 2277-8330 (Electronic) Mosawi et al.,