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* Corresponding author: Rajesh Kumar.D.
E-mail address: rajeshpharma89@gmail.com
IJAMSCR |Volume 1 | Issue 1 | Oct - 2013
www.ijamscr.com
Review article
Pachygyria: A Neurological Migration Disorder
Rajesh Kumar.D1
*, Ramu.V.V2
, Ram Sarath Kumar.B3
, Sumalatha.N3
Murali.G4
, Prathap
Reddy.P5
1*
Department of Pharmacology, Siddhartha Institute of Pharmaceutical Sciences, Narsaraopet.
Guntur (Dt).
2
Nova College of Pharmacy, Vijayawada, A.P.
3
Sims College of Pharmacy, Guntur, A.P.
4
Sai Aditya Institute of pharmaceutical Sciences, Vijayawada, A.P.
5
Siddhartha Institute of Pharmaceutical Sciences Vijayawada, A.P.
ABSTRACT
Pachygyria is a neuronal migration disorder characterized by thick convulsions on cerebral cortex and brain has
few gyri. It leads to mental retardation. It is also known as Macrogyria. It is considered as a rare disease. The
disease involves mutations in a number of genes. Mainly the symptoms are seizures and delayed development.
MRI and CT scan are used for diagnosis. It can be treated by anti epileptic medication and various therapies like
speech therapy and occupational therapy. G therapy is effective for the treatment. So far, there is no specific
drug treatment.
KEY WORDS: Pachygyria, Macrogyria, Mutations, Seizures and G therapy.
INTRODUCTION
Isolated Pachygyria means that only one part of the
brain is affected, extensive Pachygyria signifies
that most of the brain is absent of gyri. The
condition is closely related to lissencephaly, a term
used to describe the condition of a brain that is
completely smooth. Though in most cases it is
genetic, sometimes pachygyria can be caused by
infection early in a pregnancy. During fetal
development, neurons must migrate from their
place of origin deep inside the brain to their proper
neural circuits near the brain’s surface. Neuronal
migration, which can occur as early as the second
month of gestation, is controlled by chemical
signals. Neurons that settle outside of their
designated locations cause the brain to develop
structural abnormalities. “A neuronal migration
disorder is a disorder where the neurons do not
migrate as they should”, Paciorkowski said.
“Because the neurons are not showing up on the
surface of the brain, the surface of the brain is not
as developed as it should be and has fewer gyri.
This is a shared finding of all neuronal migration
disorders.”The extent to which a person with
Pachygyria is affected depends on how absent the
brain is from convulsions. Paciorkowski said that
in most cases, people with pachygyria have
moderate to severe developmental delay and
epilepsy. Proper brain function depends on the
correct positioning of neurons as a result of
directed migration during development. Humans
with lissencephaly/ Pachygyria are mentally
retarded and frequently suffer from epilepsy. The
disease involves mutations in a number of genes.
International Journal of Allied Medical Sciences
and Clinical Research (IJAMSCR)
Rajesh Kumar.D, et al / Int. J. of Allied Med. Sci. and Clin. Research Vol-1(1) 2013 [31-33]
www.ijamscr.com
~ 32 ~
Definition
According to Seattle Children’s pediatric
neurologist Alexander Paciorkowski, Pachygyria is
a neuronal migration disorder that results in too
few gyri, or folds in the brain. It is a Condition in
which the convolutions of the cerebral cortex are
abnormally large, there are fewer sulci than normal
and in some cases the amount of brain substance is
somewhat increased.
Synonym: Macrogyria, Incomplete lissencephaly.
History
Pachygyria is a Greek word; (from
the Greek "pachy" meaning "thick" or "fat" gyri) is
a congenital malformation of the cerebral
hemisphere. It results in unusually thick
convolutions of the cerebral cortex. It is a less
variant of lissencephaly (smooth brain)
characterized by short, broad gyri with lack of
sulcation. Pachygyria is a condition identified by a
type of cortical genetic malformation.
Symptoms
 Seizures
 Developmental delay
 Mental problems
 Poor muscle tone (hypotonia)
 Poor muscle control
 Feeding/swallowing difficulties
 Small head size (microcephaly)
 Swelling in the extremities.
Pathophysiology
Pachygyria is due to neuronal migration defects,
usually genetic or toxic in origin. Mainly R264C
alpha-tubulin mutation causes pachygyria, a
neuronal migration disease.
Another mechanism involves the architectonic
features of abnormal cerebral cortex in a brain with
lissencephaly and pachygyria suggest than neuronal
migration was interrupted by cortical and
subcortical laminar necrosis in the fourth fetal
month. The severest cortical abnormality lies in the
distal perfusion fields of the major cerebral arteries,
while the normal areas are located in the proximal
perfusion fields. These architectonic and
topographic features suggest that intra-uterine
hypoxia or perfusion failure may be a pathogenetic
mechanism leading to lissencephaly and
pachygyria. Pachygyria, lissencephaly (smooth
brain), and polymicrogyria (multiple small gyri) are
all the results of abnormal cell migration. The
abnormal migration is typically associated with a
disorganized cellular architecture, failure to form
six layers of cortical neurons (a four-layer cortex is
common), and functional problems.
Causes
There may be various possible causes of
Pachygyria, includes
 Viral infections,
 Insufficient blood flow to the brain during fetal
development or
 Certain genetic factors.
Epedimiology
Pachygyria is classified as a rare condition
.Neurologists and geneticists consider rare
conditions to arise in less than 1 in 2,000 people.
Diagnosis
Mostly the application of MRI and CT scan is
applied to understand the condition of the patients
and accordingly the treatment schedule is planned
in correlation of the symptoms and major
obstruction. Magnetic Resonance Imaging (MRI) is
commonly used for diagnosis. It provides a high
contrast image for better delineation of white and
gray matter. Pachygyria shows on an MRI as
thickened cerebral cortices with few and large gyri
and incomplete development of Sylvian fissures.
While computed tomography (CT) provides higher
spatial resolution imaging of the brain, cerebral
cortex malformations are more easily visualized.
Treatment
The treatment of Pachygyria mainly depends upon
assistive technology speech therapy, behavioral
therapy, occupational therapy, counseling,
symptomatic drug therapy for convulsions,
involuntary movements etc. and surgery for
corrective measures. However these therapies and
cognitive interventions may vary from one patient
to another depending on level of complications and
age. So far there is no drug therapy available to
improve motor functions and higher cortical
functions of the brain.
Pachygyria is basically a structural defect; therefore
specific treatment of this pachygyria is still not
available especially of associated seizure problem.
Treatment of pachygyria may include the treatment
of gastronomy, the process involves the insertion of
a feeding tube in order to reduce possible
malnutrition and repeated spell of aspiration
pneumonia in the affected child. However,
gastronomical intervention may not be the
treatment of the prime disease but it is a kind of
Rajesh Kumar.D, , et al / Int. J. of Allied Med. Sci. and Clin. Research Vol-1(1) 2013 [31-33]
www.ijamscr.com
~ 33 ~
back- up for the immunity of the concerned child in
order to make the health system comparatively
robust and scale of immunity can be improved.
G Therapy has shown positive effects in a few
cases in the treatment of pachygyria. Changes in
patients after G Therapy treatment for Pachygyria
include improvements in muscle tone,
understanding, speech and other global
improvements. It is a pioneering homeopathic
medical combination treatment for variety of
neurological conditions. The complete name of this
form of treatment is "Homeo-Biochemic
Formulation Therapy", it was formulated by Dr
Gunvant Oswal from the University of Pune in
India. G-Therapy is part of the Ayurvedic
medicine, it is essentially based on a remedy whose
substance is extracted from plants. The remedy is
diluted according to the homeopathic process
which states that the higher a substance is diluted
the greater its effects will be and added to
biochemical salts or body salts. The final product is
available in form of tablets and like homeopathic
remedies; the tablets have to be taken sublingually
(under the tongue). The mechanism of action of G
Therapy can be explained according to the
principles of homeopathy, where in biochemical
remedies reactivate the chemical changes for
neurotransmission, while the homeopathic
remedies act as catalyst to speed up the
improvement.
REFERENCES
[1] Francis F., Meyer G., Fallet-Bianco C., Moreno S., Kappeler C., Socorro A. C., Tuy F. P., Beldjord C.,
Chelly J. Human disorders of cortical development: from past to present. Eur. J.
Neurosci. 2006;23:877–893. [PubMed]
[2] Gao Y., Thomas J. O., Chow R. L., Lee G. H., Cowan N. J. A cytoplasmic chaperonin that catalyzes
beta-actin folding. Cell. 1992;69:1043–1050.[PubMed]
[3] Gdalyahu A., Ghosh I., Levy T., Sapir T., Sapoznik S., Fishler Y., Azoulai D., Reiner O. DCX, a new
mediator of the JNK pathway. EMBO J.2004;23:823–832. [PMC free article] [PubMed]
[4] Gleeson J. G., et al. Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and
double cortex syndrome, encodes a putative signaling protein. Cell. 1998; 92:63–72. [PubMed]
[5] Grishchuk E. L., McIntosh J. R. Sto1p, a fission yeast protein similar to tubulin folding cofactor E,
plays an essential role in mitotic microtubule assembly. J. Cell Sci. 1999;112:1979–1988. [PubMed]
[6] Poirier, Gray, and Escourolle. Manual of Basic Neuropathology 1990. pp 200.
[7] Cotran, Kumar, and Robbins. Pathologic Basis of Disease 5th edition. pp 1302.
[8] Barkovich AJ, Kjos BO. Gray matter heterotopias: MR characteristics and correlation with
developmental and neurologic manifestations. Radiology. 1992;182 (2): 493-Radiology (abstract) -
Pubmed citation
[9] Abdel razek AA, Kandell AY, Elsorogy LG et-al. Disorders of cortical formation: MR imaging
features. AJNR Am J Neuroradiol. 2009;30 (1): 4-11. doi:10.3174/ajnr.A1223 -Pubmed citation
[10] Grainger & Allison's Diagnostic Radiology: A Textbook of Medical Imaging, 4th ed. 2001.
[11] Rarediseases.info.nih.gov.
[12] www.diseaseinfosearch.org.
[13] en.wikipedia.org.
************************

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Pachygyria a neurological migration disorder

  • 1. ~ 31 ~ * Corresponding author: Rajesh Kumar.D. E-mail address: rajeshpharma89@gmail.com IJAMSCR |Volume 1 | Issue 1 | Oct - 2013 www.ijamscr.com Review article Pachygyria: A Neurological Migration Disorder Rajesh Kumar.D1 *, Ramu.V.V2 , Ram Sarath Kumar.B3 , Sumalatha.N3 Murali.G4 , Prathap Reddy.P5 1* Department of Pharmacology, Siddhartha Institute of Pharmaceutical Sciences, Narsaraopet. Guntur (Dt). 2 Nova College of Pharmacy, Vijayawada, A.P. 3 Sims College of Pharmacy, Guntur, A.P. 4 Sai Aditya Institute of pharmaceutical Sciences, Vijayawada, A.P. 5 Siddhartha Institute of Pharmaceutical Sciences Vijayawada, A.P. ABSTRACT Pachygyria is a neuronal migration disorder characterized by thick convulsions on cerebral cortex and brain has few gyri. It leads to mental retardation. It is also known as Macrogyria. It is considered as a rare disease. The disease involves mutations in a number of genes. Mainly the symptoms are seizures and delayed development. MRI and CT scan are used for diagnosis. It can be treated by anti epileptic medication and various therapies like speech therapy and occupational therapy. G therapy is effective for the treatment. So far, there is no specific drug treatment. KEY WORDS: Pachygyria, Macrogyria, Mutations, Seizures and G therapy. INTRODUCTION Isolated Pachygyria means that only one part of the brain is affected, extensive Pachygyria signifies that most of the brain is absent of gyri. The condition is closely related to lissencephaly, a term used to describe the condition of a brain that is completely smooth. Though in most cases it is genetic, sometimes pachygyria can be caused by infection early in a pregnancy. During fetal development, neurons must migrate from their place of origin deep inside the brain to their proper neural circuits near the brain’s surface. Neuronal migration, which can occur as early as the second month of gestation, is controlled by chemical signals. Neurons that settle outside of their designated locations cause the brain to develop structural abnormalities. “A neuronal migration disorder is a disorder where the neurons do not migrate as they should”, Paciorkowski said. “Because the neurons are not showing up on the surface of the brain, the surface of the brain is not as developed as it should be and has fewer gyri. This is a shared finding of all neuronal migration disorders.”The extent to which a person with Pachygyria is affected depends on how absent the brain is from convulsions. Paciorkowski said that in most cases, people with pachygyria have moderate to severe developmental delay and epilepsy. Proper brain function depends on the correct positioning of neurons as a result of directed migration during development. Humans with lissencephaly/ Pachygyria are mentally retarded and frequently suffer from epilepsy. The disease involves mutations in a number of genes. International Journal of Allied Medical Sciences and Clinical Research (IJAMSCR)
  • 2. Rajesh Kumar.D, et al / Int. J. of Allied Med. Sci. and Clin. Research Vol-1(1) 2013 [31-33] www.ijamscr.com ~ 32 ~ Definition According to Seattle Children’s pediatric neurologist Alexander Paciorkowski, Pachygyria is a neuronal migration disorder that results in too few gyri, or folds in the brain. It is a Condition in which the convolutions of the cerebral cortex are abnormally large, there are fewer sulci than normal and in some cases the amount of brain substance is somewhat increased. Synonym: Macrogyria, Incomplete lissencephaly. History Pachygyria is a Greek word; (from the Greek "pachy" meaning "thick" or "fat" gyri) is a congenital malformation of the cerebral hemisphere. It results in unusually thick convolutions of the cerebral cortex. It is a less variant of lissencephaly (smooth brain) characterized by short, broad gyri with lack of sulcation. Pachygyria is a condition identified by a type of cortical genetic malformation. Symptoms  Seizures  Developmental delay  Mental problems  Poor muscle tone (hypotonia)  Poor muscle control  Feeding/swallowing difficulties  Small head size (microcephaly)  Swelling in the extremities. Pathophysiology Pachygyria is due to neuronal migration defects, usually genetic or toxic in origin. Mainly R264C alpha-tubulin mutation causes pachygyria, a neuronal migration disease. Another mechanism involves the architectonic features of abnormal cerebral cortex in a brain with lissencephaly and pachygyria suggest than neuronal migration was interrupted by cortical and subcortical laminar necrosis in the fourth fetal month. The severest cortical abnormality lies in the distal perfusion fields of the major cerebral arteries, while the normal areas are located in the proximal perfusion fields. These architectonic and topographic features suggest that intra-uterine hypoxia or perfusion failure may be a pathogenetic mechanism leading to lissencephaly and pachygyria. Pachygyria, lissencephaly (smooth brain), and polymicrogyria (multiple small gyri) are all the results of abnormal cell migration. The abnormal migration is typically associated with a disorganized cellular architecture, failure to form six layers of cortical neurons (a four-layer cortex is common), and functional problems. Causes There may be various possible causes of Pachygyria, includes  Viral infections,  Insufficient blood flow to the brain during fetal development or  Certain genetic factors. Epedimiology Pachygyria is classified as a rare condition .Neurologists and geneticists consider rare conditions to arise in less than 1 in 2,000 people. Diagnosis Mostly the application of MRI and CT scan is applied to understand the condition of the patients and accordingly the treatment schedule is planned in correlation of the symptoms and major obstruction. Magnetic Resonance Imaging (MRI) is commonly used for diagnosis. It provides a high contrast image for better delineation of white and gray matter. Pachygyria shows on an MRI as thickened cerebral cortices with few and large gyri and incomplete development of Sylvian fissures. While computed tomography (CT) provides higher spatial resolution imaging of the brain, cerebral cortex malformations are more easily visualized. Treatment The treatment of Pachygyria mainly depends upon assistive technology speech therapy, behavioral therapy, occupational therapy, counseling, symptomatic drug therapy for convulsions, involuntary movements etc. and surgery for corrective measures. However these therapies and cognitive interventions may vary from one patient to another depending on level of complications and age. So far there is no drug therapy available to improve motor functions and higher cortical functions of the brain. Pachygyria is basically a structural defect; therefore specific treatment of this pachygyria is still not available especially of associated seizure problem. Treatment of pachygyria may include the treatment of gastronomy, the process involves the insertion of a feeding tube in order to reduce possible malnutrition and repeated spell of aspiration pneumonia in the affected child. However, gastronomical intervention may not be the treatment of the prime disease but it is a kind of
  • 3. Rajesh Kumar.D, , et al / Int. J. of Allied Med. Sci. and Clin. Research Vol-1(1) 2013 [31-33] www.ijamscr.com ~ 33 ~ back- up for the immunity of the concerned child in order to make the health system comparatively robust and scale of immunity can be improved. G Therapy has shown positive effects in a few cases in the treatment of pachygyria. Changes in patients after G Therapy treatment for Pachygyria include improvements in muscle tone, understanding, speech and other global improvements. It is a pioneering homeopathic medical combination treatment for variety of neurological conditions. The complete name of this form of treatment is "Homeo-Biochemic Formulation Therapy", it was formulated by Dr Gunvant Oswal from the University of Pune in India. G-Therapy is part of the Ayurvedic medicine, it is essentially based on a remedy whose substance is extracted from plants. The remedy is diluted according to the homeopathic process which states that the higher a substance is diluted the greater its effects will be and added to biochemical salts or body salts. The final product is available in form of tablets and like homeopathic remedies; the tablets have to be taken sublingually (under the tongue). The mechanism of action of G Therapy can be explained according to the principles of homeopathy, where in biochemical remedies reactivate the chemical changes for neurotransmission, while the homeopathic remedies act as catalyst to speed up the improvement. REFERENCES [1] Francis F., Meyer G., Fallet-Bianco C., Moreno S., Kappeler C., Socorro A. C., Tuy F. P., Beldjord C., Chelly J. Human disorders of cortical development: from past to present. Eur. J. Neurosci. 2006;23:877–893. [PubMed] [2] Gao Y., Thomas J. O., Chow R. L., Lee G. H., Cowan N. J. A cytoplasmic chaperonin that catalyzes beta-actin folding. Cell. 1992;69:1043–1050.[PubMed] [3] Gdalyahu A., Ghosh I., Levy T., Sapir T., Sapoznik S., Fishler Y., Azoulai D., Reiner O. DCX, a new mediator of the JNK pathway. EMBO J.2004;23:823–832. [PMC free article] [PubMed] [4] Gleeson J. G., et al. Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein. Cell. 1998; 92:63–72. [PubMed] [5] Grishchuk E. L., McIntosh J. R. Sto1p, a fission yeast protein similar to tubulin folding cofactor E, plays an essential role in mitotic microtubule assembly. J. Cell Sci. 1999;112:1979–1988. [PubMed] [6] Poirier, Gray, and Escourolle. Manual of Basic Neuropathology 1990. pp 200. [7] Cotran, Kumar, and Robbins. Pathologic Basis of Disease 5th edition. pp 1302. [8] Barkovich AJ, Kjos BO. Gray matter heterotopias: MR characteristics and correlation with developmental and neurologic manifestations. Radiology. 1992;182 (2): 493-Radiology (abstract) - Pubmed citation [9] Abdel razek AA, Kandell AY, Elsorogy LG et-al. Disorders of cortical formation: MR imaging features. AJNR Am J Neuroradiol. 2009;30 (1): 4-11. doi:10.3174/ajnr.A1223 -Pubmed citation [10] Grainger & Allison's Diagnostic Radiology: A Textbook of Medical Imaging, 4th ed. 2001. [11] Rarediseases.info.nih.gov. [12] www.diseaseinfosearch.org. [13] en.wikipedia.org. ************************