Neurology PDF

Neurology i. Congenital Anomalies of the Central Nervous System Nelson Last Minute  Congenital Anomalies of the Central Nervous System Neural Tube Defects (Dysraphism) Failure of the neural tube to close spontaneously bet...

Neurology i. Congenital Anomalies of the Central Nervous System Nelson Last Minute  Congenital Anomalies of the Central Nervous System Neural Tube Defects (Dysraphism) Failure of the neural tube to close spontaneously between the 3rd and 4th wk of in utero development. neural tube factors, including hyperthermia, drugs, malnutrition, chemicals, maternal obesity or diabetes, and genetic determinants (mutations in folate-responsive or folate- dependent pathways) The major neural tube defects include: 1. spina bifida occulta 2. meningocele 3. myelomeningocele 4. encephalocele 5. anencephaly 6. dermal sinus 7. tethered cord 8. syringomyelia 9. diastematomyelia 10. lipoma involving the conus medullaris and/or filum terminale. In the 3rd wk of embryonic development, the neural tube is formed. Normally, the rostral end of the neural tube closes on the 23rd day and the caudal neuropore closes by the 27th day of development. Failure of closure of the neural tube allows excretion of fetal substances (α-fetoprotein [AFP], acetylcholinesterase) into the amniotic fluid, serving as biochemical markers for a neural tube defect. Prenatal screening of maternal serum for AFP in the 16th-18th wk of gestation is an effective method for identifying pregnancies at risk for fetuses with neural tube defects in utero. Spina Bifida Occulta Anomaly consists of a midline defect of the vertebral bodies without protrusion of the spinal cord or meninges. Most individuals are asymptomatic and lack neurologic signs, and the condition is usually of no consequence. patches of hair, a lipoma, discoloration of the skin, or a dermal sinus in the midline of the lower back suggests a more significant malformation of the spinal cord A spine roentgenogram in simple spina bifida occulta shows a defect in closure of the posterior vertebral arches and laminae, typically involving L5 and S1 Spina bifida occulta is associated with developmental abnormalities: syringomyelia, diastematomyelia, and a tethered cord.( occult spinal dysraphism) = usually with cutaneous manifestations. dermoid sinus a small skin opening, which leads into a narrow duct, sometimes indicated by protruding hairs, a hairy patch, or a vascular nevus.  Dermoid sinuses occur in the midline at the lumbosacral region or occiput.  Dermoid sinus tracts may pass through the dura,act as conduit for spread of infection. Meningocele When the meninges herniate through a defect in the posterior vertebral arches. The spinal cord is usually normal and assumes a normal position in the spinal canal There may be tethering, syringomyelia, or diastematomyelia. A fluctuant midline mass that may transilluminate occurs along the vertebral column, usually in the lower back. Most meningoceles are well covered with skin and pose no threat to the patient. roentgenograms, ultrasonography, and MRI ۳۰۱  Urologic evaluation, by cystometrogram (CMG), will identify those children with neurogenic bladder who are at risk for renal deterioration. Those patients with leaking cerebrospinal fluid (CSF) or a thin skin covering should undergo immediate surgical treatment to prevent meningitis. A CT scan of the head is recommended for children with a meningocele because of the association with hydrocephalus in some cases. An anterior meningocele projects into the pelvis through a defect in the sacrum.  Symptoms of constipation and bladder dysfunction develop due to the increasing size of the lesion.  Female patients may have associated anomalies of the genital tract, including a rectovaginal fistula and vaginal septa.  Plain roentgenograms demonstrate a defect in the sacrum  CT scanning or MRI outlines the extent of the meningocele. Myelomeningocele the most severe form of dysraphism involving the vertebral column and occurs Incidence ≈1/4,000 live births. The cause of myelomeningocele is unknown Genetic predisposition exists; the risk of recurrence after one affected child increases to 3-4% and increases to ≈10% with two previous abnormal pregnancies. Folate is intricately involved in the prevention and etiology of NTDs. Maternal periconceptional use of folic acid supplementation reduces 50%. (before conception - least the 12th wk of gestation) - 0.4mg of folic acid daily, if high-risk =4mg of folic acid daily 1mo before the time of the planned conception May be located anywhere along the neuraxis, but the lumbosacral region accounts for at least 75% of the cases. The extent and degree of the neurologic deficit depend on the location of the myelomeningocele, as well as the associated lesions.  A lesion in the low sacral region causes bowel and bladder incontinence associated with anesthesia in the perineal area but with no impairment of motor function.  the midlumbar region typically have a saclike cystic structure covered by a thin layer of partially epithelialized tissue ♦ Remnants of neural tissue are visible beneath the membrane, which may occasionally rupture and leak CSF. ♦ Produce lower motor neuron signs due to abnormalities and disruption of the conus medullaris. ♦ flaccid paralysis of the lower extremities, an absence of deep tendon reflexes, a lack of response to touch and pain, and a high incidence of lower extremity deformities (clubfeet, subluxation of the hips). ♦ Constant urinary dribbling and a relaxed anal sphincter may be evident.  increasing neurologic deficit as the myelomeningocele extends higher into the thoracic region  In the upper thoracic or the cervical region usually have a very minimal neurologic deficit and, in most cases, do not have hydrocephalus. Hydrocephalus in association with a type II Chiari defect develops in at least 80% of patients with myelomeningocele.  the lower the deformity in the neuraxis (sacrum), the less likely is the risk of hydrocephalus.  Ventricular enlargement may be indolent and slow growing or may be rapid: ♦ Bulging anterior fontanel, dilated scalp veins, setting-sun appearance of the eyes, irritability, and vomiting, increased head circumference. ♦ About 15% of infants with hydrocephalus and Chiari II malformation develop symptoms of hindbrain dysfunction (difficulty feeding, choking, stridor, apnea, vocal cord paralysis, pooling of secretions, and spasticity of the upper extremities) if untreated death. ♦ This Chiari crisis is due to downward herniation of the medulla and cerebellar tonsils through the foramen magnum. ۳۰۲  Surgery is often done within a day or so of birth but can be delayed for several days (except when there is a CSF leak) After repair of a myelomeningocele, most infants require a shunting procedure for hydrocephalus. reassessment of the genitourinary system (regularly catheterize a neurogenic bladder  low residual volume and bladder pressure t prevents UTI and reflux leading to pyelonephritis, hydronephrosis, and bladder damage) incontinence of fecal matter is common  fecal impaction and/or megacolon the mortality rate is ≈10-15%, and most deaths occur before age 4yr At least 70% of survivors have normal intelligence Renal dysfunction is one of the most important determinants of mortality. Encephalocele Two major forms of dysraphism affect the skull, resulting in protrusion of tissue through a bony midline defect( cranium bifidum) 1. cranial meningocele consists of a CSF-filled meningeal sac only 2. cranial encephalocele contains the sac plus cerebral cortex, cerebellum, or portions of the brainstem. The cranial defect occurs most commonly in the occipital region at or below the inion, but in certain parts of the world, frontal or nasofrontal encephaloceles are more prominent Are at increased risk for developing hydrocephalus due to aqueduct stenosis, Chiari malformation, or the Dandy-Walker syndrome. Examination: small sac with a pedunculated stalk or a large cystlike structure that may exceed the size of the cranium. Investigations: 1. A plain roentgenogram of the skull and cervical spine  anatomy of the vertebrae. 2. Ultrasonography  the contents of the sac. 3. MRI or CT further  the spectrum of the lesion. Meckel-Gruber syndrome is a rare autosomal recessive condition 1. occipital encephalocele 2. cleft lip or palate 3. microcephaly 4. microphthalmia 5. abnormal genitalia 6. polycystic kidneys 7. polydactyly Perinatal diagnosis: 1. maternal serum α-fetoprotein levels 2. ultrasound measurement of the biparietal diameter , identification of the encephalocele itself. Polycystic kidney polyductyly encephalocele Prognosis: disease 1. cranial meningocele  good prognosis 2. encephalocele : at risk of visual problems, microcephaly, mental retardation, seizures. 3. cranial encephalocele and hydrocephalus have the poorest prognosis. Anencephaly a large defect of the calvarium, meninges, and scalp associated with a rudimentary brain, which results from failure of closure of the rostral neuropore, the opening of the anterior neural tube. recurrence risk is ≈4% and increases to 10% if a couple has had two previously affected pregnancies. 50% of cases of anencephaly have associated Note: polyhydramnios.  Lissencephaly: no brain sulcation, seizure Most infants die within several days of birth +developmental retardation, chromosomal  Schizenecephaly: symmetrical bilateral cleft extend from cerebral cortex to ventricles, severe mental and motor retardation.  Holoprosenecephalus: failure of cerebral vesicle to divide, associated with midline fascial defects: hypotolerism, cleft lip, cleft palate. isolated or chromosomal. ۳۰۳  Microcephaly Head circumference that measures more than three standard deviations below the mean for age and sex. main groups: 1. primary (genetic) microcephaly : associated with a specific genetic syndrome, familial and autosomal dominant microcephaly, 2. secondary (nongenetic) microcephaly: large number of noxious agents that affect a fetus in utero or an infant during periods of rapid brain growth( 1st 2yr of life) Family history for additional cases of microcephaly or disorders affecting the nervous system. The head circumference of each parent and sibling should be recorded. Inv: 1. mother's serum phenylalanine level should be determined. High phenylalanine serum levels in an asymptomatic mother can produce marked brain damage in an otherwise normal nonphenylketonuric infant. 2. karyotype if a chromosomal syndrome is suspected or if the child has abnormal facies, short stature, and additional congenital anomalies. 3. MRI is useful in identifying structural abnormalities of the brain 4. CT scanning is useful to detect intracerebral calcification. 5. fasting plasma and urine amino acid analysis 6. serum ammonia determination 7. toxoplasmosis, rubella, cytomegalovirus, and herpes simplex (TORCH) titers as well as HIV testing of the mother and child; and a urine sample for the culture of cytomegalovirus. CAUSES CHARACTERISTIC FINDINGS PRIMARY (GENETIC) 1. Familial (autosomal severely mentally retarded and prominent seizures. Typical recessive)- microcephaly vera appearance with slanted forehead, prominent nose and ears 2. Autosomal dominant Nondistinctive facies, upslanting palpebral fissures, mild forehead slanting, and prominent ears Normal linear growth, seizures readily controlled, and mild or borderline mental retardation 3. Syndromes Down (21-trisomy) Abnormal rounding of occipital and frontal lobes and a small cerebellum Edward (18-trisomy) Low birthweight, microstomia, micrognathia, low-set malformed ears, prominent occiput, rocker-bottom feet, flexion deformities of fingers, congenital heart disease Cri-du-chat (5 p-) Round facies, prominent epicanthic folds, low-set ears, hypertelorism, and characteristic cry No specific neuropathology Cornelia de Lange Rubinstein-Taybi ۳۰٤  Smith-Lemli-Opitz Low birthweight, marked feeding problems SECONDARY (NONGENETIC) 1. Radiation Microcephaly and mental retardation most severe if exposure before 15th wk of gestation 2. Congenital infections Cytomegalovirus Small for dates, petechial rash, hepatosplenomegaly, chorioretinitis, deafness, mental retardation, and seizures Central nervous system calcification and microgyria Rubella Growth retardation, purpura, thrombocytopenia, hepatosplenomegaly, congenital heart disease, chorioretinitis, cataracts, and deafness Toxoplasmosis Purpura, hepatosplenomegaly, jaundice, convulsions, hydrocephalus, chorioretinitis, and cerebral calciffication 3. Drugs Fetal alcohol Growth retardation, ptosis, absent philtrum and hypoplastic upper lip, congenital heart disease, feeding problems Fetal hydantoin Growth delay, hypoplasia of distal phalanges, inner epicanthic folds, broad nasal ridge, and anteverted nostrils 4. Meningitis/encephalitis Cerebral infarcts, cystic cavitation, diffuse loss of neurons 5. Malnutrition Controversial cause of microcephaly 6. Metabolic Maternal DM and maternal hyperphenylalaninemia 7. Hyperthermia Significant fever during 1st 4-6 wk has been reported to cause microcephaly, seizures, and facial anomalies Further studies showed no abnormalities with maternal fever 8. Hypoxic-ischemic Initially diffuse cerebral edema; late stages characterized by cerebral encephalopathy atrophy PRIMARY Craniosynostosis Craniosynostosis is defined as premature closure of the cranial sutures and is Classified: 1. Primary craniosynostosis : closure of one or more sutures due to abnormalities of skull development 2. secondary craniosynostosis results from failure Note: of brain growth and expansion Secondary causes: Incidence of primary craniosynostosis approximates  Metabolic disorders (hyperthyroidism 1/2,000 births ,Mucopolysaccharidosis  Malformations (holoprosencephaly, microcephaly, shunted hydrocephalus, encephalocele)  valproic acid, phenytoin ۳۰٥  The cause is unknown in the majority of children, genetic syndromes account for 10-20% of cases. Most cases are evident at birth and are characterized by a skull deformity FORMS: 1. scaphocephaly:  The most common form of craniosynostosis.  Premature closure of the sagittal suture produces a long and narrow skull  Associated with a prominent occiput, a broad forehead, and a small or absent anterior fontanel.  The condition is sporadic, more common in males 80%  Causes difficulties during labor because of cephalopelvic disproportion.  Does not produce increased ICP or hydrocephalus, normal neurologic examination 2. Frontal plagiocephaly:  the next most common form of craniosynostosis  Result of premature fusion of a coronal and sphenofrontal suture.  Characterized by unilateral flattening of the forehead, elevation of the ipsilateral orbit and eyebrow, and a prominent ear on the corresponding side.  The condition is more common in females  Surgical intervention produces a cosmetically pleasing result. 3. Occipital plagiocephaly:  most often a result of positioning during infancy – need positional maneuvers only  more common in an immobile or handicapped child  Fusion or sclerosis of the lambdoid suture cause unilateral occipital flattening and bulging of the ipsilateral frontal bone. 4. Trigonocephaly:  Rare form of craniosynostosis due to premature fusion of the metopic suture.  a keel-shaped forehead and hypotelorism  At risk for associated developmental abnormalities of the forebrain. 5. Turricephaly :  Cone-shaped head due to premature fusion of the coronal and often sphenofrontal and frontoethmoidal sutures. 6. kleeblattschädel deformity:  skull resembles a cloverleaf.  Affected children have very prominent temporal bones, and the remainder of the cranium is constricted.  Hydrocephalus is a common complication The most prevalent genetic disorders associated with craniosynostosis: 1. Crouzon syndrome: inherited as an autosomal dominant trait. The shape of the head most often is brachycephaly. The orbits are underdeveloped, and ocular proptosis is prominent. Hypoplasia of the maxilla and orbital hypertelorism are typical facial features. 2. Apert syndrome: sporadic condition,may AD. associated with premature fusion of multiple sutures,The facies tend to be asymmetric, eyes are less proptotic than in Crouzon syndrome. Apert syndrome is characterized by syndactyly of the 2nd, 3rd, and 4th fingers, which may be joined to the thumb and the 5th finger also occur in the feet. All patients have progressive calcification and fusion of the bones of the hands, U feet, and cervical spine. 3. Carpenter syndrome :autosomal recessive, klee-blattschädel skull deformity. Soft tissue syndactyly of the hands and feet is always present, and mental retardation is U U common. 4. Chotzen syndrome is characterized by asymmetric craniosynostosis and U plagiocephaly. The condition is the most prevalent of the genetic syndromes U and is inherited as an autosomal dominant trait. facial asymmetry, ptosis of the eyelids, shortened fingers, syndactyly of the 2nd and 3rd fingers. 5. Pfeiffer syndrome is most often associated with turricephaly. The eyes are U U prominent and widely spaced, and the thumbs and great toes are short and broad. Partial soft tissue syndactyly may be evident. Most cases appear to be sporadic. ۳۰٦  TREATMENT:  Premature fusion of only one suture rarely causes a neurologic deficit  the sole indication for surgery is child's cosmetic appearance  when two or more sutures are prematurely fused, Neurologic complications, including hydrocephalus and increased ICP may occuroperative intervention is essential.  The best time to intervene is when the infant is between 3-9 months of age (less than 1 year).  Infants with increased intracranial pressure require urgent decompression. Note: differences deformational lambdoid synostosis plagiocephaly posterior bossing absent contralateral and parietal frontal bossing Ipsilateral, absent or contralateral prominent ipsilateral ear anterior displaced posteriorly displacement toward the fused suture Crouzon syndrome Apert syndrome Carpenter syndrome ۳۰۷ Hydrocephalus: Cfs:  Formed primarily in the ventricular system by the choroid plexus, which is situated in the lateral, 3rd, and 4th ventricles.  most CSF is produced in the lateral ventricles, ≈25% originates from extrachoroidal sources( brain capillaries)  Adrenergic system ↓ CSF production, cholinergic nerves↑ the normal CSF production.  The total volume of CSF: 50mL in an infant and 150mL in an adult.  CSF flows from the lateral ventricles  foramina of Monro the 3rd ventricle aqueduct of Sylvius 4th ventricle paired lateral foramina of Luschka and the midline foramen of Magendie  cisterns at the base of the brain over the convexities of the cerebral hemispheres absorbed by arachnoid villi. Hydrocephalus: 1. obstructive or non-communicating hydrocephalus: obstruction within the ventricular system  Most commonly in children because of an abnormality of the aqueduct stenosis( sex-linked recessive or infectious- intrauterine infections &mumps ) or a lesion in the 4th ventricle.  Others: posterior fossa brain tumors,Dandy-Walker malformation, Chiari malformation, 2. nonobstructive or communicating hydrocephalus: obliteration of the subarachnoid cisterns or malfunction of the arachnoid villi.  most commonly follows a subarachnoid hemorrhage  others: leukemic infiltrates, Pneumococcal and tuberculous meningitis clinical features:  In an infant: 1. accelerated rate of enlargement of the head is the most prominent sign 2. the anterior fontanel is wide open and bulging 3. the scalp veins are dilated 4. The forehead is broad 5. the setting-sun eye sign. 6. Long-tract signs: brisk tendon reflexes, spasticity, clonus (particularly in the lower extremities), and Babinski sign.  In an older child: 1. Irritability, lethargy, poor appetite, and vomiting are common to both age groups 2. Headache is a prominent symptom in older patients. 3. A gradual change in personality and a deterioration in academic productivity. 4. Increase velocity of head circumference growth. 5. Macewen sign: skull Percussion produce cracked pot sound  sutures separation 6. occiput: flat  Chiari malformation, prominent  Dandy-Walker malformation. 7. Papilledema, abducens nerve palsy, and UMN are apparent in most cases. Multiple café-au-lait spots and other clinical features of neurofibromatosis point to aqueductal stenosis as the cause of hydrocephalus. type II Chiari malformation is characterized by progressive hydrocephalus with a myelomeningocele. Dandy-Walker malformation consists of triad: complete or partial agenesisi of th vermis, cystic dilatation of the 4 ventricle, enlarged posterior fossa. 90% of patients have P P hydrocephalus. managed by shunting the cystic cavity. D/D: 1. Hydranencephaly : The cerebral hemispheres are absent or represented by membranous sacs with remnants of cortex dispersed over the membrane. 2. Familial megalencephaly: autosomal dominant trait , characterized by delayed motor milestones and hypotonia , normal or near-normal intelligence. # parents' head circumference for diagnosis. 3. megalencephaly. Ex: lysosomal diseases (Tay-Sachs, mucopolysaccharidoses), the aminoacidurias (maple syrup urine disease), leukodystrophies, genatics causes( cerebral gigantism (sotos syndrome) and neurofibromatosis/ + Mental R.) ۳۰۸  4. thickened cranium : chronic anemia, rickets, osteogenesis imperfecta, and epiphyseal dysplasia. Treatment:  Therapy for hydrocephalus depends on the cause.  Medical management, acetazolamide and furosemide, provide temporary relief by ↓rate of CSF production.  Most cases of hydrocephalus require extracranial shunts,ex: ventriculoperitoneal shunt. The major complications of shunting are : 1. occlusion (characterized by headache, papilledema, emesis, mental status changes) 2. bacterial infection (fever, headache, meningismus), Staphylococcus epidermidis Neurocutaneous Disorders dermatological and neurological manifestations. the most common neurocutaneous disorders are: 1. Neurofibromatosis 2. Tuberous sclerosis 3. Sturge-Weber disease 4. Von Hippel-Lindau disease 5. Ataxia-telangiectasia Arise from a defect in differentiation of the primitive ectoderm except:. von Hippel-Lindau disease and Sturge-Weber disease (mesenchymal origin) von Hippel-Lindau disease has no characteristic cutaneous lesions. phakomatosis : "mother spots" or "birthmarks" and refers to tuberous sclerosis and NF NEUROFIBROMATOSIS von Reckling-hausen disease NF-1 (1 in 3000) diagnosed when 2/7 signs are present: 1. Six or more café-au-lait macules over 5mm in greatest diameter in prepubertal and over 15mm in greatest diameter in postpubertal. present 100% of patients. On trunk and extremities, sparing of the face. 2. Axillary or inguinal freckling : multiple hyperpigmented areas 2-3mm in diameter. 3. Two or more iris Lisch nodules. hamartomas located within the iris , identified by a slit-lamp examination. >74% with NF-1. prevalence Note: increases with age 90% of adults / 25% of children Scoliosis is the most 4. Two or more neurofibromas or one plexiform neurofibroma. common orthopedic a. Neurofibromas : involve the skin, or along peripheral nerves and manifestation of NF-1, blood vessels and viscera. Appear characteristically during although it is not specific adolescence or pregnancy. small, rubbery lesions with a slight enough to be included purplish discoloration of the overlying skin. as a diagnostic criterion. b. Plexiform neurofibromas :evident at birth and result from diffuse thickening of nerve trunks that are frequently located in the orbital or temporal region of the face. The skin overlying is hyperpigmented to a greater degree than a café-au-lait spot. Plexiform neurofibromas produce overgrowth of an extremity U and a deformity of the corresponding bone. U 5. A distinctive osseous lesion such as sphenoid dysplasia (which may cause pulsating exophthalmos) or cortical thinning of long bones with or without pseudoarthrosis. 6. Optic gliomas ≈15% of patients with NF-1. Most are asymptomatic with normal or near- normal vision, but ≈20% have visual disturbances or precocious sexual development secondary to tumor invasion of the hypothalamus. 7. first-degree relative with NF-1 Patients with NF-1 are at risk for hypertension, which may result from renal vascular stenosis or a pheochromocytoma. ۳۰۹  segmental neurofibromatosis: Somatic mosaicism, in which an abnormality in one copy of the NF1 gene is present in some cells but not others, indicates a postzygotic mutation. NF-2 accounts for 10% of all cases of NF  incidence of 1/50,000( NF2 gene mutation)  diagnosed when one of the following two features : 1. bilateral eighth nerve masses consistent with acoustic neuromas as demonstrated by CT scanning or MRI. 2. A parent, sibling, or child with NF-2 and either unilateral eighth nerve masses or any two of the following: ♦ neurofibroma, meningioma, glioma, schwannoma, or juvenile posterior subcapsular lenticular opacities≈50%.  Bilateral acoustic neuromas are the most distinctive feature of NF-2.  Symptoms of hearing loss, facial weakness, headache, or unsteadiness may appear during childhood  café-au-lait spots and skin neurofibromas are classic findings in NF-1, they are much less common in NF-2. As with NF-1, CNS tumors, including Schwann cell and glial tumors, and meningiomas are common in patients with NF-2. The average life span is less than 40 years. complications : 2. learning disability 3. scoliosis 4. macrocephaly 5. headache 6. peripheral nerve malignancy 7. pheochromocytoma 8. re-novascular hypertension 9. epilepsy 10. Malignancy is the most common cause of death. STURGE-WEBER SYNDROME Sturge-Weber syndrome is sporadic and not genetic. characterized by angiomas of the leptomeninges overlying the cerebral cortex in + ipsilateral facial port-wine nevus that at the least, covers part of the forehead and upper eyelid. The nevus may more extensive and with bilateral distribution. ( ectasia of superficial venules, not a hemangioma, because it has no endothelial proliferation). Ocular defects of Sturge-Weber syndrome include: 1. glaucoma: 30% to 50%, progressive. 2. hemangiomas of the choroid, conjunctiva, and episclera. seizuresThe most common associated neurologic abnormality. Due to brain ischemic injury by the meningeal angiomas.  most patients in the 1st year of life  They are focal tonic-clonic and contralateral to the side of the facial nevus. mental retardation is commonin ,at least 50% in later childhood. Angiomas, most commonly located in the posterior parietal, posterior temporal, and anterior occipital lobes, within the pia mater.  hemiparesis, hemianopia, intractable focal seizures, and dementia. "tram track" or "railroad track" calcifications is seen in about 60% of cases. ۳۱۰ TUBEROUS SCLEROSIS autosomal dominant disorder characterized by hamartomas in many organs, especially the brain, eye, skin, kidneys, and heart. incidence is 1 in 10,000 births 2/3 sporadic ,Germline mosaicism is uncommon ( explains normal parents with affected children). Clinical Manifestations extremely heterogeneous disease with a wide clinical spectrum varying from severe mental retardation and seizures  normal intelligence and no seizures. The classic clinical features are: 1. facial angiofibromas (adenoma sebaceum) 2. mental retardation 3. Severe epilepsy. < 50% of patients exhibit all three features. major signs are: 1. ungual fibromas 2. retinal hamartomas 3. hypopigmented macules 4. shagreen patches :plaques of skin specially lumbar and gluteal regions, develop in late childhood or early adolescence. 5. Sebaceous adenomas develop between 4 and 6yr of age; they appear as tiny red nodules over the nose and cheeks 6. Renal angiomyolipoma: may undergo malignant transformation , most common cause of death in adults with tuberous sclerosis. 7. cardiac rhabdomyoma 50% :largest in prenatal life & infancy, rarely symptomatic. 8. brain tubers: The characteristic brain lesion is a cortical tuber. 9. brain subependymal nodules 10. astrocytomas. 11. ash-leaf spots 90%:hypomelanotic macules, called, are present in infancy and best detected with a Wood lamp under UV light. Tuberous sclerosis is one of the most common causes of infantile spasms= intractable epilepsy, mental retardation; autism, hyperactivity. directly by MRI and indirectly by CT, shows periventricular calcifications within the nodule, especially around the foramen of Monro. ۳۱۱  Febrile Seizures Benign convulsions by any viral illness except: CNS disease, infection or metabolic disorders. Seizures not caused by fever or viral toxin. The most common seizure disorder during childhood. the incidence approaches 3–4% of young children. The peak age of onset is 14–18 mo of age. rare < 9 mo and > 5 yr of age. Each child with a seizure + fever  carefully examined and investigated for the cause of the fever. Have an excellent prognosis but may also signify a serious underlying acute infectious disease such as sepsis or bacterial meningitis. A strong family history of febrile convulsions  genetic predisposition.  AD inheritance pattern is demonstrated in some families. d/d : 1. Febrile convulsion 2. epilepsy caused by fever 3. CNS infection Clinical Manifestations. Associated with rapidly raising temperature when core temperature = ≥39°C. Simple complex Pattern Generalized Partial/focal Duration Brief15 min Occurrence in 24 Once > 1 attack hours Neurological Normal compromised statue History of febrile Negative positive convulsion 30–50% of children have recurrent seizures with later episodes of fever. RISKS: 1. age