Craniosynostosis

CraniosynostosisSurgical Treatment & Neurodevelopmental Outcome

Devon M. Fagel, J.D.Clinical Neuroscience Clerkship

February 5, 2010

Learning Objectives

• Recognize the early presentation of skull deformities

• Describe the differential diagnosis of craniosynostosis

• Review calvarial anatomy and suture pathophysiology

• Interpret the epidemiology of nonsyndromic synostosis

• Learn the surgical techniques for correcting synostosis

• Review the complications and post-op management

• Evaluate the data on neurodevelopmental outcomes

• HPI: Full-term M infant presents for monitoring following episode of hypoglycemia (stabilized to 58 w/o intervention).

• PMH: No prenatal/birth complications.

• FH: No hx of craniofacial disorders.• PE:

• Vitals: HR: 150 RR: 48 BP:75/38 SpO2: 100% Temp: 98.7

• Measure: Length: 48.9cm Weight: 3.1kg Head Circumference: 34cm

• CV: RRR, no m/r/g, 2+ pulses AFE, plethoric color

• GI/GU: Abd soft, no masses, + BS, urine/meconium not passed

• MS: Spine straight, upper/lower ext appear normal w full ROM

• Neuro: +Moro reflex, normal tone, spontaneous activity, strong cry

Case PresentationAdmission to NBSCU - Day 4

• PE: • HEENT:

• Head: Symmetrical, central forehead angular vertical prominence

• Fontanels: Normal, flat and soft

• Sutures: Normal, approximated

• Face: Symmetrical

• Eyes: Clear, +red reflex

• Ears: Normal shape and position

• Nose: Patent nares

• Mouth: Palate intact, normal tongue

• Neck: Normal, supple

Case PresentationAdmission to NBSCU - Day 4

Differential DiagnosisNonsyndromic Seconday Craniosynostosis

• Metabolic Disorders

• Rickets

• Hyperthyroidism

• Hematological Disorders

• Thalassemias

• Sickle cell anemia

• Polycythemia vera

• Lysosomal Storage Disorders

• Sly Syndrome

• Hurler Syndrome

• Morquio Syndrome

• Teratogens

• Phenytoin

• Valproic Acid

• Retinoic Acid

• Aminopterin

• Malformations

• Microcephaly

• Encephalocele

• Shunted Hydrocephalus

• Positional Etiology

• Fetal Head Restraints

• Deformational Plagiocephaly

Differential DiagnosisSyndromic Primary Craniosynostosis

Syndrome Gene Additional Symptoms

Apert FGFR2 syndactyly, flat midface

CrouzonFGFR2,

3orbital hypertelorism, flat face

Muenke FGFR3 skeletal abnormalities hands/feet, hearing loss

PfeifferFGFR1,

2syndactyly, short thumbs/big toes

Jackson-Weiss

FGFR1,2 enlarged, varus big toes

Calvarial Anatomy

Suture Pathophysiology

Sagittal Scaphocephaly 50-60%

Unilateral Coronal

Frontal Plagiocephaly

20-30%

Bilateral Coronal Turribrachycephaly 10-15%Metopic Trigonocephaly 5-10%

Unilateral Lambdoid

Posterior Plagiocephaly

2-4%

Bilateral Lambdoid Brachycephaly ?

Suture Pathophysiology• Skull begins developing between 23-26d gestation.

• Ossification begins, forming the cranial vault bones at 2m.

• Margins of these bones host osteoprogenitors with deposition by osteoblasts and remodeling by osteoclasts to form sutures.

• Dura is essential for immature sutures to develop normally. When neonatal rat dura was transplanted into subcutaneous tissue, bone was formed. But when placed under sutures it resisted ossification and formed cartilage.

• FGFRs play critical role in osteoblast proliferation (R2) and differentiation (R1). FGFR2 is absent in the suture and dura but highly expressed in bone fronts.

Epidemiology• Incidence ranges from 3-10 per 10,000 live births.

• Of those, 2-8% have primary craniosynostosis.

• More than 90% of those occur spontaneously.

• 8-10% of coronal synostosis patients have +FH.

• 1-2% of sagital synostosis patients have +FH.

• Some patients misdiagnosed non-syndromic due to extreme variability of some Mendelian syndromes.

• Incidence of Apert syndrome 1 per 200,000 births.

• More than 98% of posterior plagiocephaly cases due to positional molding with increasing rates since Back to Sleep Campaign in 1992.

Case PresentationWorkup for Craniosynostosis - Day 54

Case PresentationWorkup for Craniosynostosis - Day 54

Metopic Synostosis

Surgery Indications • Signs of Elevated Intracranial Pressure

• 14% of single suture synostosis had elevated ICP

• 47% of multiple suture synostosis had elevated ICP

• Symptoms include HA, emesis, visual defects, AMS

• Most consistent finding is papilledema/optic nerve atrophy

• Radiological signs are narrow ventricles, sulcal effacement

• Ongiong debate about behavioral and cognitive deficits

• Cosmetic Considerations

• Calvarial deformity affects psychosocial development

• Untreated pts more likely to suffer personality disorders

• Deformities may also lead to proptosis and strabismus

Surgery Indications • Cosmetic Considerations

• Deformities may also lead to proptosis and strabismus

• Calvarial deformity affects psychosocial development

• Untreated pts more likely to suffer personality disorders

Correction of Metopic Synostosis

• Bifrontal craniotomy and bilateral supraorbital rim osteotomy. Frontal bone remolded to eliminate frontal keel and triangular shape. Supra-orbital rim also remodeled.

• Parallel osteotomies created in the parietal region for lateral expansion.

• Supraorbital rim is advanced.

• Reshaped frontal bone attached to the underlying dura and supraorbital rim.

Case PresentationPost-Op Imaging - 4 Months

Case PresentationPost-Op Management

• HPI: s/p cranioplasty post-op day 0. Patient received 750cc crystalloid and 300cc blood during procedure. Hct in OR was 34, dropped to 31 on arrival to PICU.

• PE: • Vitals: HR: 166 RR: 32 BP:82/69 SpO2: 95% Temp: 96.6

• HEENT: surgical incisions over parietal/occipital lobe c/d/i

• Lungs: CTAB, no tachypnea, no retractions

• CV: RRR, no m/r/g, pale, warm, cap refill <3s

• Neuro: Grasping dad’s hand, intermittently opens eyes, PERRLA

Neurodevelopment in SSC

• Assumption is that ICP increases with restricted cranial growth and in turn adversely influences mental development, yet in SSC patency of remaining sutures should allow for adequate decompression.

• Though may expect decrease in intracranial volume, data suggests that brain volume in SSC is normal or exceeds normal limits.

• Shape may also play critical role as changes in normal spacial relations may affect neural organizational networks.

• Metopic synostosis patients have been found to exhibit corpus callosum anomalies and abnormally small frontal lobes as well as enlargement of the subarachnoid space in the areas of compensatory bone expansion likely due to fluid shifts.

• Though linear distances between and among structures were altered after corrective surgery, these relations were still abnormal.

Effects on Brain Structure

Neurodevelopment in SSC

• A review of 17 studies between 1972-2003 found that the majority of children demonstrated global development within normal range, however 35-40% showed more subtle learning disability, language impairment or “behavioral or cognitive abnormality.”

• Among several quasi-experimental studies of cranioplastic surgery there is little evidence that intervention either prevented or reduced risk of neurobehavioral impairment.

• Warschausky et al examined 22 infants with isolated metopic synostosis before surgery using the Bayley scales of infant development (problem-solving skills) and a psychomotor development index. Scores were within normal range.

• Kapp-Simon et al recently reported data on first 100 patients in a prospective longitudinal study with 24 metopic cases. Assessing infants with BSID and PDI as well as preschool language scale-3, study found that those with SSC had scores 1-2 standard deviations below normal, regardless of subgroup.

Effects on Neurobehavioral Outcomes

Mechanism???

While it has been hypothesized that increasing ICP and other structural changes caused by SSC are responsible for

neurodevelopmental deficits, we must consider the possibility that SSC and the neuropsychological deficits

may both stem from a primary malformation of the brain.

FGF Pathway• FGF induces

proliferation, migration, differentiation leading to neurogenesis and angiogenesis.

• FGFs bind to activate the Raf1-MEK-MAPK and PI3K pathway for proper mesoderm development (bones and cartilage).

• Mutations in genes encoding FGFR1,2,3 cause both dwarfing chondrodysplagia and craniosynostosis syndromes.

FGFR1 in Neurodevelopment

Increase in FGFR1 After Hypoxia

FGFR1 & Migration

FGFR1 & Differentiation

FGFR1 & Proliferation

Review• Distinguish between primary vs secondary, syndromic vs

nonsyndromic and craniosynostosis vs positional DP.

• Sagital and unilateral coronal synostosis are the most common deformities accounting for 80-90% of patients.

• Dura is essential for immature sutures to develop normally. FGFRs play critical role in proliferation and differentiation.

• Indications for surgery include increased ICP (papilledema) and cosmetic considerations (psychosocial development).

• Correction of metopic synostosis includes bifrontal craniotomy and remodeling to eliminate triangular shape and parietal barrel stave osteotomy to allow for lateral expansion.

• Suture fusion may lead to behavioral and cognitive deficits or genetic mutations in growth factor genes may cause both fused sutures and developmental disabilities in parallel.

References• Persing, JA, Jane, JA. Craniosynostosis. In: Youmans J. ed Neurological

Surgery. 4th ed. Philadelphia: WB Saunders; 1996: 995-1011.

• Ocal, E et al., Craniosynostosis. In: Albright, A. ed Principles and Practice of Pediatric Neurosurgery. 2nd ed. New York: Thieme Medical Publishers; 2008: 265-288.

• Kimonis et al., Genetics of Craniosynostosis. Semin Pediatr Neurol 14: 150-61, 2007.

• Kapp-Simon et al., Neurodevelopment of Chilren with Single Suture Craniosynostosis: A Review. Childs Nerv Syst 23: 269-281, 2007.

• Starr et al., Presurgical and Postsurgical Assessment of the Neurodevelopment of Infants with Single-Suture Craniosynostosis: Comparison with Controls. J Neurosurg 107: 103-110, 2007.

• Magge et al., Long-term Neuropsychological Effects of Sagittal Cranio-synostosis on Child Development. J Craniofac Surg 13: 99-104, 2002.

• Fagel et al., Cortical Neurogenesis Enhanced by Chronic Perinatal Hypoxia. Exp Neurol 199: 77-91, 2006

• Fagel et al., FGFR1 is Required for Cortical Regeneration and Repair After Perinatal Hypoxia. J Neurosci 29: 1202-1211, 2009