Cerebrospinal malformations Notes

NOTES NOTES CEREBROSPINAL MALFORMATIONS GENERALLY, WHAT ARE THEY? PATHOLOGY & CAUSES ▪ Disorders affecting normative central nervous system (CNS) development/ function ▪ Varying severity, intensity CAUSES ▪ Primary ▫ Genetic mutation/idiopathic ▪ Secondary ▫ E.g. trauma, infection, neoplasm, environmental factors RISK FACTORS ▪ Cerebral ischemia, delivery trauma, premature birth, teratogenic substance exposure (prenatal) ▪ Supportive structure (bone, connective tissue) malformation → physically obstructs CNS development SIGNS & SYMPTOMS ▪ Developmental milestones ▫ Not met ▪ Motor dysfunction ▫ Ataxia, paresis, unsteady gait, speech impairment, poor coordination ▪ Dysautonomia ▪ Intellectual disability ▫ Learning/memory issues ▪ Dementia DIAGNOSIS DIAGNOSTIC IMAGING ▪ CT scan, MRI OTHER DIAGNOSTICS ▪ Neurological exam TREATMENT ▪ Mostly supportive SURGERY ▪ In some cases; see individual disorders OSMOSIS.ORG 513

ARNOLD–CHIARI MALFORMATION osms.it/arnold-chiari-malformation PATHOLOGY & CAUSES SIGNS & SYMPTOMS ▪ Insufficient posterior fossa growth → developmental cerebellum, brainstem, craniocervical junction malformation ▪ Affects cerebellar structure, position ▪ AKA Chiari malformation type II (types I, III, IV—no specific name) ▪ Chiari malformations: similar presentations, different mechanism development ▪ Accompanying findings: aqueductal stenosis, upward cerebellar displacement, cerebellar dysplasia ▪ Cerebellar tonsil protrusion through foramen magnum ▪ Associations: lumbosacral myelomeningocele, Pierre Robin syndrome, neurofibromatosis type I, Noonan syndrome ▪ Commonly accompanies spina bifida ▪ Nausea, vertigo, nystagmus, unsteady gait ▪ Lumbosacral/thoracic myelomeningocele presence ▪ Medulla oblongata compression → dysautonomia (↓ ↑ heart/breathing rate, neurogenic bladder, sleep apnea, pupillary dilation, etc.) ▪ Paralysis/dysesthesia below spinal compression ▪ Valsalva maneuver → symptoms worsen (increased intracranial pressure) RISK FACTORS ▪ Hydrocephalus (congenital/acquired) ▪ Ehlers–Danlos syndrome, Marfan syndrome → craniocervical joint instability → cerebellar tonsil displacement ▪ Posterior cranial fossa malformation (agenesia, craniosynostosis, osteopetrosis) ▪ Posterior cranial fossa pathology (tumor, abscess, cyst, hematoma) COMPLICATIONS ▪ Aqueductal stenosis → impaired CSF flow → non-communicating hydrocephalus → lateral, third ventricle dilatation ▪ Fourth ventricle obstruction → noncommunicating hydrocephalus → aqueduct dilatation; lateral, third ventricles ▪ Brainstem, spinal cord compression ▪ Syringomyelia (hydrocephalus → distention, dilation of spinal cord’s central canal) 514 OSMOSIS.ORG DIAGNOSIS DIAGNOSTIC IMAGING CT scan, MRI ▪ Findings include presence of myelomeningocele, cerebellar tissue (downward displacement) through foramen magnum, small fourth ventricle, tectal beaking, atlas assimilation OTHER DIAGNOSTICS ▪ Neurological exam TREATMENT SURGERY ▪ Open neural tube defect closure ▪ Shunt placement (relieves hydrocephalus) ▪ Bone removal (↓ brain structure pressure) OTHER INTERVENTIONS ▪ Address complications: neurogenic bowel, bladder; neonatal feeding difficulty; respiratory failure, apnea

Chapter 66 Cerebrospinal Malformations Figure 66.1 An MRI scan of the head in the sagittal plane of an individual with an Arnold-Chiari malformation. There is a small posterior fossa and partial descent of the brainstem and the cerebellar tonsils through the foramen magnum. CEREBRAL PALSY (CP) osms.it/cerebral-palsy PATHOLOGY & CAUSES ▪ Wide disorder group; non-progressive cerebral lesions impair motor, postural function/muscle tone ▪ Most common motor disorder, 2.1 per 1000 babies affected, ages 0–3 years ▪ Varying severity, complexity ▪ Often accompanied by mental function impairment, epilepsy MNEMONIC: PALSY Main characteristcs of CP Paresis Ataxia Lagging motor development Spasticity Young CAUSES ▪ Primary: genetic (autosomal recessive glutamate decarboxylase-1 deficiency) ▪ Secondary: preterm birth (most common cause), CNS injury, intrauterine growth restriction, intrauterine infection, antepartum hemorrhage, severe placental pathology, multiple pregnancy RISK FACTORS ▪ Prenatal/perinatal ▫ CNS trauma (pregnancy/birth) ▫ Cerebrovascular insult (infarction, thrombosis, hypoxic-ischemic injury) ▫ CNS infection ▫ Radiation exposure ▫ Methylmercury/alcohol (prenatal exposure) ▫ Maternal smoking/obesity ▫ Infections during pregnancy OSMOSIS.ORG 515

▪ Postnatal ▫ Stroke, CNS trauma, hypoxia (drowning), sepsis/meningitis, kernicterus SIGNS & SYMPTOMS ▪ Motor symptoms (type-dependent) ▫ Paresis, ataxia, spasticity, irregular posture, orthopedic contracture, scoliosis, seizure, neurogenic bladder/ bowel, impaired vision/speech, difficulty feeding/swallowing DIAGNOSIS DIAGNOSTIC IMAGING CT scan, MRI ▪ Type-dependent ▫ Hypoxic-ischemic lesions (e.g. periventricular leukomalacia/basal ganglia lesions); cortical malformation; hydrocephalus Ultrasound ▪ In young infants with open anterior fontanelle OTHER DIAGNOSTICS ▪ Neurological exam ▪ Diagnostic tests ▫ Differentiate from other motor dysfunction disorders (e.g metabolic disorders, stroke, hydrocephalus, hematomas) 516 OSMOSIS.ORG TREATMENT ▪ No definitive treatment MEDICATIONS ▪ Benzodiazepines → myorelaxation, anxiety relief ▪ Spasmolytics → muscle-spasticity relief ▪ Anticonvulsants → seizure treatment, prevention ▪ Pain medication SURGERY ▪ Posture correction OTHER INTERVENTIONS ▪ Physical, occupational, speech therapy ▪ Posture correction ▫ Braces/other orthotic devices

Chapter 66 Cerebrospinal Malformations DANDY–WALKER SYNDROME (DWS) osms.it/dandy-Walker-malformation PATHOLOGY & CAUSES ▪ Neurodevelopmental disorders; affect cerebellar vermis, fourth ventricle ▪ Classical triad ▫ Vermis hypoplasia/agenesis, cystic dilatation (fourth ventricle), posterior fossa enlargement ▪ Accompanying disorders (wide range) ▫ Cortical dysplasia, syringomyelia, schizencephaly, corpus callosum dysgenesis, cleft palate, etc. ▪ Associated with posterior fossa malformations–hemangiomas– arterial anomalies–cardiac defects– eye abnormalities–sternal cleft and supraumbilical raphe syndrome (PHACES) MNEMONIC: DWS Components of DWS Dilated 4th ventricle Water on the brain Small vermis CAUSES ▪ Genetic, environmental factors ▫ Meckel syndrome ▫ Chromosomal aneuploidy (e.g. 45X, triploidy) ▫ Rubella infection/warfarin exposure during pregnancy ▫ Maternal alcohol consumption ▫ Congenital heart defect ▫ Neural tube defect ▫ Holoprosencephaly COMPLICATIONS ▪ Foramina (Magendie, Luschka) atresia → hydrocephalus SIGNS & SYMPTOMS ▪ Macrocephaly, developmental milestones not met (mental, motor), impaired motor coordination, unsteady gait, seizure, lower limb spasticity, eye/ear involvement (rarely) OSMOSIS.ORG 517

DIAGNOSIS DIAGNOSTIC IMAGING MRI, prenatal ultrasound ▪ Characteristic findings ▫ Cerebellar vermis agenesis/hypoplasia, cystic dilatation (fourth ventricle), posterior fossa enlargement; hydrocephalus, absent corpus callosum may also be present LAB RESULTS ▪ Amniocentesis Figure 66.2 An MRI scan of the head in the sagittal plane demonstrating a Dandy-Walker malformation in a one-year-old boy. There is accompanying gross hydrocephalus. 518 OSMOSIS.ORG TREATMENT ▪ No definitive treatment SURGERY Ventricular-peritoneal shunt ▪ Manages hydrocephalus OTHER INTERVENTIONS ▪ Physical, occupational therapy

Chapter 66 Cerebrospinal Malformations NORMAL PRESSURE HYDROCEPHALUS (NPH) osms.it/normal-pressure-hydrocephalus PATHOLOGY & CAUSES ▪ Cerebrospinal fluid (CSF) accumulation → progressive lateral ventricle enlargement ▪ AKA Hakim’s syndrome ▪ Intracranial pressure (ICP) not normal (name is misnomer) OTHER DIAGNOSTICS ▪ High-volume lumbar puncture/lumbar drain trial ▫ Improved functionality with CSF removal ▪ Neurological exam TREATMENT SURGERY CAUSES ▪ Slight–moderate elevation → classical ↑ ICP symptoms (nausea, vomiting, photophobia, neck pain, stiffness) not evident ▪ ↑ CSF → ↑ ICP → lateral ventricle dilation → pressure on corona radiata ▫ Urinary incontinence), brainstem structure (magnetic gait), periventricular limbic system (dementia) ▪ Idiopathic/secondary ▫ Cerebrovascular insult, meningitis, trauma, tumor ▪ In some situations Ventriculoperitoneal shunt ▪ ↑ ICP relief RISK FACTORS ▪ Prevalence largest among elderly (common onset approx. 60 years old) SIGNS & SYMPTOMS ▪ Unsteady gait ▫ Described as magnetic or “glue-footed” ▪ Urinary incontinence ▪ Cognitive impairment DIAGNOSIS Figure 66.3 An MRI scan of the head in the sagittal plane demonstrating hydrocephalus. There is a prominent flow void in the sylvian aqueduct, suggesting a normal-pressure hydrocephalus. DIAGNOSTIC IMAGING MRI/CT scan ▪ Ventriculomegaly, enlarged Sylvian fissures, enlarged sulci with no cortical atrophy OSMOSIS.ORG 519

RETT SYNDROME osms.it/rett-syndrome PATHOLOGY & CAUSES RISK FACTORS ▪ Rare neurological disorder, impairs motor function (eating, walking, talking, breathing) ▪ AKA cerebroatrophic hyperammonemia ▪ Associated with prolonged QT syndrome ▪ Young, individuals who are biologically female ▪ Extraordinarily, individuals who are biologically male with Klinefelter syndrome (XXY), otherwise fatal for biologically-male (XY) individuals CAUSES COMPLICATIONS ▪ X-linked autosomal dominant MeCP2 gene mutation (spontaneous) ▪ MeCP2 protein involved in forming neuronal connections, when only one gene is mutated, the other one can compensate to a degree 520 OSMOSIS.ORG Growth failure Seizure Fractures (related to ↓ bone mineralization) Cardiac abnormalities; e.g. prolonged QTc interval ▪ Autonomic nervous system dysfunction ▪ Sleep disturbances ▪ Behavioral issues; e.g. clapping, “pill-rolling” (due to extrapyramidal motor defects) ▪ ▪ ▪ ▪

Chapter 66 Cerebrospinal Malformations TREATMENT SIGNS & SYMPTOMS ▪ Manifests after six months old → later, divided into four stages DIAGNOSIS LAB RESULTS ▪ No definitive treatment MEDICATIONS ▪ SSRI (behavioral issues) OTHER INTERVENTIONS ▪ Genetic test ▫ MeCP2 mutation ▪ Occupational, speech, physical therapy ▪ Nutritional support for fracture reduction OTHER DIAGNOSTICS ▪ Clinically diagnosed (characteristic findings) ▫ Loss of acquired purposeful hand skills, spoken language ▫ Gait abnormalities ▫ Stereotypic hand movements SEPTO-OPTIC DYSPLASIA (SOD) osms.it/septo-optic-dysplasia PATHOLOGY & CAUSES ▪ Congenital malformation triad ▫ Underdeveloped optic nerve, hypopituitarism, absent septum pellucidum ▪ AKA de Morsier syndrome ▪ Most individuals have two of three components, some present with all three ▪ May also have encephalomalacia, schizencephaly, ectopic pituitary tissue CAUSES ▪ Genetic ▫ Spontaneous/inherited HESX1, OTX2, SOX2, PAX6 mutation ▪ In utero sodium valproate, cocaine exposure SIGNS & SYMPTOMS Nystagmus Visual impairment Intellectual impairment Seizure Growth hormone deficiency → short stature, hypoglycemia, micropenis (if biologically-male) ▪ Vasopressin deficiency → diabetes insipidus ▪ Hyperprolactinemia ▪ Hyperbilirubinemia → jaundice ▪ ▪ ▪ ▪ ▪ DIAGNOSIS DIAGNOSTIC IMAGING MRI ▪ Optic nerve hypoplasia, septum pellucidum, corpus callosum agenesis OSMOSIS.ORG 521

LAB RESULTS Genetic testing ▪ HESX1, OTX2, SOX2, PAX6 mutations OTHER DIAGNOSTICS ▪ Neurological exam TREATMENT MEDICATIONS ▪ Hormone replacement therapy ▪ Anticonvulsants → seizure treatment, prevention OTHER INTERVENTIONS ▪ Treat complications ▫ Ophthalmic, physical, and occupational therapy Figure 66.4 An MRI scan of the head in the coronal plane of an individual with septooptic dysplasia. The septum pellucidum, which normally separates the two lateral ventricles, is absent. SPINA BIFIDA osms.it/spina-bifida PATHOLOGY & CAUSES ▪ Congenital spinal column, meninges malformation ▪ Most common neural tube defect ▪ Improper vertebrae formation allows meninges/spinal cord to protrude dorsally out of spinal canal ▪ Occurs in fourth week of pregnancy ▪ Usually manifests in lumbar part of spinal column (can occur elsewhere) ▪ Most individuals with spina bifida have latex allergy (complicates medical procedures) ▪ Some individuals with spina bifida have intellectual impairment ▪ Can present with Arnold–Chiari malformation ▪ Associated with malformed corpus callosum, cerebellum, cerebral cortex 522 OSMOSIS.ORG RISK FACTORS ▪ Multifactorial ▫ Genetic, environmental factors ▪ Pregnancy ▫ Folate deficiency, anticonvulsant use ▪ Obesity ▪ Poorly-managed diabetes mellitus COMPLICATIONS ▪ Meningitis; neurogenic bladder, bowel; nerve damage paralysis; tethered cord syndrome; cognitive impairment; pressure ulcer; seizure; hydrocephalus; orthopedic problems SIGNS & SYMPTOMS ▪ Lower-back pain, hip dysplasia, dysesthesia (below lesion), leg weakness, nystagmus, clubfoot, scoliosis

Chapter 66 Cerebrospinal Malformations DIAGNOSIS DIAGNOSTIC IMAGING Prenatal ultrasound OTHER INTERVENTIONS ▪ Resolve complications ▫ Seizure, hydrocephalus, orthopedic problems ▪ Physical therapy X-ray, CT scan, MRI ▪ Show improper vertebral formation LAB RESULTS ▪ ↑ alpha-fetoprotein ▫ Spina bifida occulta does not show ↑ ▪ Genetic tests OTHER DIAGNOSTICS ▪ Visual examination ▫ Visible meningocele, myelomeningocele at birth TREATMENT SURGERY ▪ Reposition meninges, spinal cord into spinal canal Figure 66.5 An individual with spina bifida and a an associated myelomeningocoele, also known as spina bifida cystica. OSMOSIS.ORG 523

SYRINGOMYELIA osms.it/syringomyelia PATHOLOGY & CAUSES ▪ Cerebrospinal fluid-filled cyst around spinal cord’s central canal ▪ Cyst in nerve tissue (syrinx); spinal cord (myelia) ▫ E.g. brainstem syrinx (syringobulbia) ▪ As cyst forms, grows → fluid collects within spinal cord tissue → ↑ pressure within spinal cord → damage ▪ Symptoms progress slowly, often adult diagnosis TREATMENT SURGERY ▪ Cyst drainage; flow restoration RISK FACTORS ▪ Congenital: Arnold–Chiari malformation, genetic mutation ▪ Acquired: trauma; spinal cord tumor, bleeding; scoliosis SIGNS & SYMPTOMS ▪ Various locations, syringomyelia severity ▪ Chronic pain, dysesthesia, paresis/paralysis ▪ Suspended sensory level ▫ Sensory perception defect only on body parts innervated by syringomyeliaaffected structures DIAGNOSIS DIAGNOSTIC IMAGING MRI ▪ Syrinx visualization in spine OTHER DIAGNOSTICS Neurological exam ▪ For suspended sensory level 524 OSMOSIS.ORG Figure 66.6 An MRI scan of the head and neck in the sagittal plane demonstrating syringomyelia extending from approximately the level of C4 to T3. There is also a Chiari I malformation.

Chapter 66 Cerebrospinal Malformations TETHERED SPINAL CORD SYNDROME (TCS) osms.it/tethered-spinal-cord-syndrome PATHOLOGY & CAUSES ▪ Pathological spinal cord fixation to spinal canal wall ▪ AKA occult spinal dysraphism sequence ▪ Spinal cord movement restricted ▫ Normally, spinal cord floats freely in CSF ▫ TCS: restricted movement → physical strain → spinal cord damage CAUSES ▪ Primary: congenital short filum terminale ▪ Secondary: surgery/trauma → scar tissue attachment; (myelo)meningocele SIGNS & SYMPTOMS ▪ Lower-back pain, scoliosis, clubfoot, neurogenic bladder, bowel, paresis/ paralysis below lesion DIAGNOSIS DIAGNOSTIC IMAGING Spinal MRI ▪ Conus medullaris located below the normal L2–3 level Figure 66.7 An MRI scan of the spine in the sagittal plane demonstrating a tethered spinal cord associated with a lipoma of the filum terminale. TREATMENT SURGERY ▪ Relieve spinal cord strain (if possible) ▪ Corrective orthopedic surgery OTHER INTERVENTIONS ▪ Physical therapy OTHER DIAGNOSTICS ▪ Neurological exam OSMOSIS.ORG 525