Malformations.pdf

CENTRAL NERVOUS CENTRAL NERVOUS

SYSTEM MALFORMATIONS SYSTEM MALFORMATIONS

Oana TartaOana Tarta--ArseneArsene

DEPARMENT OF PEDIATRIC NEUROLOGYDEPARMENT OF PEDIATRIC NEUROLOGY

PSYCHIATRY CLINICAL HOSPITAL “AL. OBREGIA”PSYCHIATRY CLINICAL HOSPITAL “AL. OBREGIA”

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DefinitiDefinitionon

Morphologic anomalies secondary to:Morphologic anomalies secondary to:

–– Stopping in development orStopping in development or

–– Abnormal developmentAbnormal development

Central nervous structures before birth;Central nervous structures before birth;

–– Various clinical syndromes;Various clinical syndromes;

–– Different causes:Different causes:

Environmental causes (80%)Environmental causes (80%)

–– Physical agents: traumatisms, XPhysical agents: traumatisms, X--rays radiations etc;rays radiations etc;

–– Infectious agents: TORCH;Infectious agents: TORCH;

–– Metabolic agents: phenilcetonuria, mellitus diabetes etc;Metabolic agents: phenilcetonuria, mellitus diabetes etc;

–– Toxic: CO, ethylic alcohol etc;Toxic: CO, ethylic alcohol etc;

Intrinsic factors (20%): genetic factors;Intrinsic factors (20%): genetic factors;

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Normal development of CNSNormal development of CNS

1. DORSAL INDUCTION:1. DORSAL INDUCTION:

–– Neural plate (thickening of Neural plate (thickening of

the ectoderm under the ectoderm under

induction of the notochord) induction of the notochord)

→→ neural groove neural groove →→ neural neural

crest crest →→ closed (Neural closed (Neural

tube) 4 wktube) 4 wk

Anterior 24Anterior 24--26 day;26 day;

Posterior 26Posterior 26--29 day;29 day;

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NORMAL DEVELOPMENT OF THE CNSNORMAL DEVELOPMENT OF THE CNS

2. VENTRAL INDUCTION (302. VENTRAL INDUCTION (30--90 days)90 days)

–– 3 vesicles:3 vesicles:

Prosencephalon Prosencephalon →→ telencephalic vesicles telencephalic vesicles →→ cerebral hemispheres;cerebral hemispheres;

→→ diencephalon;diencephalon;

Mezencephalon Mezencephalon →→ mmidbrain;idbrain;

RombencephalonRombencephalon→→ metencephalon (pons & cerebellum)metencephalon (pons & cerebellum)

→→ mielencephalon (medulla)mielencephalon (medulla)

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NORMAL DEVELOPMENT OF THE CNSNORMAL DEVELOPMENT OF THE CNS

3. NEURONAL AND GLIAL 3. NEURONAL AND GLIAL

PROLIFERATION:PROLIFERATION:

→→ birth;birth;

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ABNORMAL DEVELOPMENT OF THE CNSABNORMAL DEVELOPMENT OF THE CNS

1. DORSAL INDUCTION (1. DORSAL INDUCTION (→→ 4 wk4 wk))

–– Disorders of the neurulation Disorders of the neurulation –– ANENCEPHALYANENCEPHALY;;

–– Disorders of the closing of the neural tube Disorders of the closing of the neural tube –– DYSRAPHISM;DYSRAPHISM;

–– Disorders of the developing of the cervical somites Disorders of the developing of the cervical somites –– ARNOLDARNOLD--CHIARI SDR.;CHIARI SDR.;

2. VENTRAL INDUCTION (2. VENTRAL INDUCTION (→→ 12 wk)12 wk)

–– Disorders of segmentation and cleavage Disorders of segmentation and cleavage ––HOLOPROSENCEPHALY;HOLOPROSENCEPHALY;

3. CORTICAL DEVELOPMENT (3. CORTICAL DEVELOPMENT (→→ birth)birth)

–– Disorders of neuronal migration and cortex structure Disorders of neuronal migration and cortex structure ––LISSENCEPHALY, POLYMICROGYRIA, NEURONAL LISSENCEPHALY, POLYMICROGYRIA, NEURONAL HETEROTOPY, CORTICAL DYSPLASIA;HETEROTOPY, CORTICAL DYSPLASIA;

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DISORDERS OF THE DORSAL DISORDERS OF THE DORSAL

INDUCTIONINDUCTION

ANENCEPHALYANENCEPHALY

–– Lethal condition characterized by Lethal condition characterized by

absence of both cerebral hemisphere absence of both cerebral hemisphere

and skull;and skull;

–– Clinical data:Clinical data:

NewNew--born only with visceroskull born only with visceroskull

(face eyes);(face eyes);

Survive days Survive days –– 2 wks;2 wks;

Some stereotypic movements, Some stereotypic movements,

spontaneously, few archaic spontaneously, few archaic

reflexes (Moro);reflexes (Moro);

–– Diagnosis:Diagnosis:

antenatal: ecography + antenatal: ecography + ↑↑ levels of levels of

alphaalpha--fetoprotein + amniocentesisfetoprotein + amniocentesis;;

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INDUCTIONINDUCTION

DYSRAPHISM:DYSRAPHISM:

–– Imperfect formation of the midline mesenchymal, bony and Imperfect formation of the midline mesenchymal, bony and neural structures secondary to imperfect closing the neural neural structures secondary to imperfect closing the neural tube;tube;

Classification:Classification:

1.1. Type of structure herniated:Type of structure herniated:

1.1. Meanings: meningocele;Meanings: meningocele;

2.2. Nervous tissue + meninges: Nervous tissue + meninges: encephalocele/myelomeningocele;encephalocele/myelomeningocele;

2.2. Localization: Localization:

1.1. Cranial: encephalocele/ meningocele;Cranial: encephalocele/ meningocele;

2.2. Spinal: spina bifida cystica / occulta;Spinal: spina bifida cystica / occulta;

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INDUCTIONINDUCTION

CRANIAL: herniation of the nervous tissues +/CRANIAL: herniation of the nervous tissues +/-- meninges meninges outside the skull;outside the skull;

Classification (type of tissue):Classification (type of tissue):

–– Cranial meingocele: covered / not by abnormal skin (hemangioma Cranial meingocele: covered / not by abnormal skin (hemangioma etc);etc);

–– Encephalocele (associate frequent with hydrocephaly):Encephalocele (associate frequent with hydrocephaly):

Post (85%): supra / infratenthorial;Post (85%): supra / infratenthorial;

Ant (15%): sphenoid / ethmoidal etc;Ant (15%): sphenoid / ethmoidal etc;

Para clinical diagnosis:Para clinical diagnosis:–– Rx, CT, MRI;Rx, CT, MRI;

–– AlphaAlpha--fetoprotein (mother + amniotic liquid);fetoprotein (mother + amniotic liquid);

Clinical signs (depending of the herniated tissue):Clinical signs (depending of the herniated tissue):

–– pyramidal s, mental retardation, epilepsy, visual deficiencies epyramidal s, mental retardation, epilepsy, visual deficiencies etc;tc;

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INDUCTIONINDUCTIONSPINALSPINAL

1.1. SPINA BIFIDA CYSTICA (herniation of the nervous tissue)SPINA BIFIDA CYSTICA (herniation of the nervous tissue)

Meningocele;Meningocele;

Localization: thoracoLocalization: thoraco--lombar/lombolombar/lombo--sacral;sacral;

Clinical data: frequent no signs, high risk of infection;Clinical data: frequent no signs, high risk of infection;

Myelomenigocele (95%):Myelomenigocele (95%):

Localization: lomboLocalization: lombo--sacral / rare cervical;sacral / rare cervical;

Clinical data:Clinical data:

Frequent uncovered by skin, only abnormal meninges;Frequent uncovered by skin, only abnormal meninges;

Motor signs:Motor signs:

Lower unit motor s. (peripheral nerve impairment);Lower unit motor s. (peripheral nerve impairment);

Upper unit motor s. (spinal cord impairment);Upper unit motor s. (spinal cord impairment);

Sphincter disturbances;Sphincter disturbances;

Sensitive s.;Sensitive s.;

Hydrocephalus;Hydrocephalus;

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INDUCTIONINDUCTION

1.1. SPINA BIFIDA CYSTICA (herniation of the nervous SPINA BIFIDA CYSTICA (herniation of the nervous

tissue)tissue)

Diagnosis:Diagnosis:

Imagistic : ecography, Rx, CT, IRM;Imagistic : ecography, Rx, CT, IRM;

↑↑ alphaalpha--fetoproteinfetoprotein;;

Treat: surgical, < 3 mo;Treat: surgical, < 3 mo;

Prevention:Prevention:

folic acid 1 mo before + 2 mo of pregnancy;folic acid 1 mo before + 2 mo of pregnancy;

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INDUCTIONINDUCTION

2.2. SPINA BIFIDA OCCULTA:SPINA BIFIDA OCCULTA:

Def: no herniation of the nervous tissue but:Def: no herniation of the nervous tissue but:

More vertebras affected;More vertebras affected;

Neurological signs secondary to medullar impairment;Neurological signs secondary to medullar impairment;

DD: simple osseous defect at 10% of children, asymptomatic;DD: simple osseous defect at 10% of children, asymptomatic;

Diagnosis:Diagnosis:

Skin signs:Skin signs:nevus, dermal sinuses, deviation of the interfesier fold skin, hnevus, dermal sinuses, deviation of the interfesier fold skin, hair zone, air zone, hemangioma etc;hemangioma etc;

Neurological s.: no / mild / severe, progressive;Neurological s.: no / mild / severe, progressive;Asymptomatic Asymptomatic →→ progressive symptomatic secondary to the growing progressive symptomatic secondary to the growing of the spinal cord;of the spinal cord;

Orthopedic + sphincter s;Orthopedic + sphincter s;

Imagistic s.: Rx / CT / MRI;Imagistic s.: Rx / CT / MRI;

Treat: surgical;Treat: surgical;

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INDUCTIONINDUCTION

2.2. SPINA BIFIDA OCCULTA:SPINA BIFIDA OCCULTA:

Types:Types:

1.1. SHORT FILUM TERMINALE:SHORT FILUM TERMINALE:

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INDUCTIONINDUCTION

2. SPINAL LIPOMAS (most frequent):2. SPINAL LIPOMAS (most frequent):

–– Collection of fat and connective tissue partially Collection of fat and connective tissue partially

encapsulated and associated with failure of fusion of thee encapsulated and associated with failure of fusion of thee

posterior bony structures;posterior bony structures;

–– Spinal cord is fixed to the meninges and skin; Spinal cord is fixed to the meninges and skin;

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INDUCTIONINDUCTION

3. DORSAL DERMAL SINUSES:3. DORSAL DERMAL SINUSES:

–– EpitheliumEpithelium--lined dermal tubes that courses from the skin lined dermal tubes that courses from the skin

surfaces toward CNS;surfaces toward CNS;

–– Complication: INFECTIOUS (recurrent meningitis + Complication: INFECTIOUS (recurrent meningitis +

hydrocephalus);hydrocephalus);

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INDUCTIONINDUCTION

4. DIASTEMATOMYELIA:4. DIASTEMATOMYELIA:Sagittal cleft dividing the spinal cord into 2 “halfSagittal cleft dividing the spinal cord into 2 “half--cords” cords” each surrounded by its own pia matter; each surrounded by its own pia matter;

5. DIPLOMYELIA:5. DIPLOMYELIA:–– Double of the spinal cord up to 10 segments, frequent Double of the spinal cord up to 10 segments, frequent

asymptomatic;asymptomatic;

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ABNORMALITIES OF THE DEVELOPMENT OF ABNORMALITIES OF THE DEVELOPMENT OF

THE CERVICAL SOMITESTHE CERVICAL SOMITES

ARNOLDARNOLD--CHIARI sdr.:CHIARI sdr.:

–– Abnormal position of the junction between medulla and spinal Abnormal position of the junction between medulla and spinal cord and also cerebellum in rapport to the foramen magnum;cord and also cerebellum in rapport to the foramen magnum;

–– Types:Types:

Type I: caudal displacement of the lower poles of cerebellum Type I: caudal displacement of the lower poles of cerebellum hemispheres up to C3;hemispheres up to C3;

–– symptomatic in adolescence;symptomatic in adolescence;

–– Recurrent headache, stiff neck;Recurrent headache, stiff neck;

–– Impairment of cranial nv (medulla) +Cerebellar s. + signs of Impairment of cranial nv (medulla) +Cerebellar s. + signs of spinal cord compression;spinal cord compression;

Type II: caudal displacement of the medulla and the lower part Type II: caudal displacement of the medulla and the lower part of the pons along with the cerebellar hemispheres;of the pons along with the cerebellar hemispheres;

–– Symptomatic: early;Symptomatic: early;

–– Associated with hydrocephalus & myelomeningocele;Associated with hydrocephalus & myelomeningocele;

–– Cerebellar s. + cranial nv s. + s. of spinal cord compression;Cerebellar s. + cranial nv s. + s. of spinal cord compression;

Type III, IV;Type III, IV;

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Disorders of segmentation and Disorders of segmentation and

cleavagecleavageHOLOPROZENCEPHALY (abnormal cleavage of the telencephalon in 5HOLOPROZENCEPHALY (abnormal cleavage of the telencephalon in 5--6 6 wk)wk)

–– there are 3 types anatomicalthere are 3 types anatomical--pathological :pathological :Alobar form: total absence of cleavage;Alobar form: total absence of cleavage;

–– single cerebral hemisphere, single ventricle, absence interemispsingle cerebral hemisphere, single ventricle, absence interemispheric bonds heric bonds (corpus calosus), single optical nv;(corpus calosus), single optical nv;

Semilobar form:Semilobar form:–– failure of cleavage in anterior part of telencephalon;failure of cleavage in anterior part of telencephalon;

–– single ventricle in the horseshoe, without body corpus calosus;single ventricle in the horseshoe, without body corpus calosus;

Lobar form:Lobar form:–– Anterior defect in cleavage of cerebral hemispheres;Anterior defect in cleavage of cerebral hemispheres;

–– 2 cerebral hemispheres + neocortex frontal anterior merged + the2 cerebral hemispheres + neocortex frontal anterior merged + the rest normal;rest normal;

–– Etiology: genetically transmit (more syndromes..)Etiology: genetically transmit (more syndromes..)

–– Clinical data: dysmorphism (gigantic, cebocephaly) + Clinical data: dysmorphism (gigantic, cebocephaly) + Endocrine, neurological, mental s.Endocrine, neurological, mental s.

–– Diagnosis: MRI;Diagnosis: MRI;

–– Prognosis Prognosis –– poor;poor;

–– Treatment Treatment –– symptomatic;symptomatic;

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Disorders of neuronal migration Disorders of neuronal migration

and cortex structureand cortex structureMICROCEPHALY:MICROCEPHALY:

–– Decrease in the volume and Decrease in the volume and weight of the brain manifested weight of the brain manifested by cranial perimeter less than by cranial perimeter less than 2 standard deviations 2 standard deviations compared to the average of compared to the average of age, sex and race; age, sex and race;

MACROCEPHALY:MACROCEPHALY:

–– Increase volume and brain Increase volume and brain weight manifested by a weight manifested by a greater cranial perimeter with greater cranial perimeter with more than 2 standard more than 2 standard deviations compared to deviations compared to

average of age, sex and race;average of age, sex and race;

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Normal cranial perimeters growingNormal cranial perimeters growing

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Disorders of neuronal migration Disorders of neuronal migration

and cortex structureand cortex structure–– LISENCEPHALY (smooth brain);LISENCEPHALY (smooth brain);

–– POLYMYCROGYRIA: POLYMYCROGYRIA: neurons reach the cortex but distribute neurons reach the cortex but distribute

abnormally, smaller gyrus and larger numberabnormally, smaller gyrus and larger number; ;

–– NEURONAL HETEROTOPHY: NEURONAL HETEROTOPHY: neurons with normal structure, but neurons with normal structure, but abnormal location and impaired synaptic connections ;abnormal location and impaired synaptic connections ;

–– CORTICAL DYSPLAZIA: CORTICAL DYSPLAZIA: focal abnormality of the cerebral cortex;focal abnormality of the cerebral cortex;

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LYSENCEPHALYLYSENCEPHALY

(smooth brain);(smooth brain);

• 2 principals types:

Type I – predominantly anterior (LYSI gene)

Type II – predominantly posterior (DCX gene – X- linkage)

+ other genes...

• diagnosis – antenatal / postnatal (cerebral MRI)

• clinical signs: epilepsy, mental + motor retardation;

•Prognosis – poor;

! GENETICAL ADVICE!!

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POLYMYCROGYRIA:POLYMYCROGYRIA:neurons reach the cortex but distribute abnormally, smaller gyruneurons reach the cortex but distribute abnormally, smaller gyrus and larger s and larger

numbernumber

EPILEPSY, SPASTICITY,

MENTAL RETARDATION

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NEURONAL HETEROTOPYNEURONAL HETEROTOPY(neurons with normal structure, but abnormal location and impair(neurons with normal structure, but abnormal location and impaired ed

synaptic connections)synaptic connections)

EPILEPSY, MENTAL

RETARDATION, NEUROLOGICAL

S.

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CORTICAL DYSPLASIACORTICAL DYSPLASIA

(focal abnormality of the cerebral cortex)(focal abnormality of the cerebral cortex)

EPILEPSY RESISTANT TO

TREATMENT

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CRANIOSTENOSISCRANIOSTENOSIS

DEFINITION: premature closure of one or more cranial DEFINITION: premature closure of one or more cranial sutures in front of a developing brain, having the sutures in front of a developing brain, having the consequence of skull deformation compensation;consequence of skull deformation compensation;

Virchow's law:Virchow's law:–– the bone growth is inhibited in the perpendicular direction, witthe bone growth is inhibited in the perpendicular direction, with h

increasing compensatory parallel with closed suture!!!;increasing compensatory parallel with closed suture!!!;

Etiology:Etiology:–– Primary: anomaly of the mesenchymal matrix;Primary: anomaly of the mesenchymal matrix;

–– Secondary to mechanical disorders (shunted hydrocephalus), Secondary to mechanical disorders (shunted hydrocephalus), metabolic (vitaminmetabolic (vitamin--resistant rickets) etc.; resistant rickets) etc.;

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NORMAL SUTURES:NORMAL SUTURES:


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Metopic sutures stenosis Metopic sutures stenosis –– TRIGONOCEPHALY:TRIGONOCEPHALY:

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Coronal sutures stenosis:Coronal sutures stenosis:

–– Unilateral Unilateral –– PLAGIOCEPHALYPLAGIOCEPHALY

–– Bilateral Bilateral –– BRAHICEPHALY (BRAHICEPHALY (reduced antreduced ant--post diameter, increased post diameter, increased

transverse diameter)transverse diameter)

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Sagital sutures stenosis Sagital sutures stenosis –– SCAFOCEPHALY (increased antSCAFOCEPHALY (increased ant--post post

diameter, decreased transverse diameter);diameter, decreased transverse diameter);

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Lambdoid sutures stenosis:Lambdoid sutures stenosis:

–– Unilateral Unilateral –– PLAGYOCEPHALYPLAGYOCEPHALY

–– Bilateral Bilateral –– PAHICEPHALY (flat occipital)PAHICEPHALY (flat occipital)

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Stenosis of the coronal sutures coronal + lambdoid + sagital Stenosis of the coronal sutures coronal + lambdoid + sagital ––

OXICEPHALY (OXICEPHALY (skull very highskull very high ))

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Clinical data:Clinical data:

1.1. Dysmorphism;Dysmorphism;

2.2. Ophthalmologic signs:Ophthalmologic signs:

1.1. Mechanical disturbances: exophthalmia, hypertelorism, Mechanical disturbances: exophthalmia, hypertelorism, strabismus;strabismus;

2.2. Visual disturbances: modification of the ocular funds Visual disturbances: modification of the ocular funds (papillary edema) etc;(papillary edema) etc;

3.3. NeuroNeuro--mental signs:mental signs:

–– Hydrocephaly;Hydrocephaly;

–– Epilepsy;Epilepsy;

–– Mental retardation;Mental retardation;

4.4. Endocrinological signs:Endocrinological signs:

–– Retard in somatic development;Retard in somatic development;

–– AdiposeAdipose--genital syndrome;genital syndrome;

–– Insipid us diabetes;Insipid us diabetes;

–– Mix edema;Mix edema;

Treat: neurosurgical Treat: neurosurgical –– craniotomy in the first 3craniotomy in the first 3--6 mo of life;6 mo of life;

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TAKE HOME MESSAGES!TAKE HOME MESSAGES!

1.1. There are more cerebral and spinal malformations and There are more cerebral and spinal malformations and all are dependent on the time of insults;all are dependent on the time of insults;

2.2. Most of them have genetically predisposition Most of them have genetically predisposition →→genetically advice!genetically advice!

3.3. Clinical signs: depending on the tissue affected:Clinical signs: depending on the tissue affected:+ skin signs (dorsal induction abnormalities);+ skin signs (dorsal induction abnormalities);

+ upper motor unit signs (spinal cord cerebral abnormalities)+ upper motor unit signs (spinal cord cerebral abnormalities)

+ lower motor unit signs (spinal dysraphism);+ lower motor unit signs (spinal dysraphism);

+ mental retardation (cerebral abnormalities);+ mental retardation (cerebral abnormalities);

+ epilepsy (gray matter involvement);+ epilepsy (gray matter involvement);

4.4. Diagnosis:Diagnosis:Imagistic exams (antenatal !! + postnatal);Imagistic exams (antenatal !! + postnatal);

AlphaAlpha--fetoprotein fetoprotein –– incomplete closure of the neural tube;incomplete closure of the neural tube;

5.5. Treatment:Treatment:Symptomatic;Symptomatic;

+/+/-- Neurosurgery;Neurosurgery;

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Malformations.pdf