Chapter 13 Congenital Cerebral Impairments

Many perinatal cerebral injuries and genetic abnormalities create distinctive, lifelong neurologic, neuropsychologic, and physical impairments. Although usually apparent in infancy, some of these disorders do not become evident until childhood or adolescence. One explanation for the delay is that cerebral myelination, which begins in the third trimester of gestation and spreads from the brainstem to the cortex, is not complete until the second year of life. Another explanation is that infants and young children, despite mild brain injury, may reach their early milestones, but eventually they cannot meet the more rigorous challenges of later childhood and adolescence.

Cerebral Palsy

Cerebral palsy (CP) – a nonscientific, but generally accepted term – describes the permanent, nonprogressive neurologic motor system impairments that result from injuries of the immature brain during fetal development (in utero), delivery, infancy, or early childhood. In addition, a variety of nonmotor problems often accompany but fall outside of the operational definition of CP. These problems include epilepsy, deficits in vision and hearing, intelligence quotient (IQ) scores below 85, poor school performance, and impaired social skills.

Neurologists attribute most cases of CP to prematurity and low birth weight, particularly weights less than 1.5 kg. Among premature infants, periventricular leukomalacia (damage of the white matter around the lateral ventricles) is the predominant pathology. Other risk factors for developing CP include hypoxia before or during labor, prolonged bradycardia, 10- or 15-minute Apgar score of less than 4, in utero intracerebral hemorrhage, perinatal ischemia, and postpartum multisystem organ failure. Over the last 40 years, improved prenatal, obstetric, and postpartum care has reduced the incidence of CP to about 2% of births. Nevertheless, CP remains the most common explanation of pediatric motor impairments, in part because of the modern-day survival rate of infants with very low birth weight.

Preventable obstetric injuries, such as anoxia, account for less than 10% of cases. In contrast, unalterable antepartum factors account for more than 70%. For example, CP is often a manifestation of genetic or congenital malformations, such as microgyria (small cerebral gyri), pachygyria (thickened gyri), hydrocephalus, and porencephaly (see Fig. 20-4). Also, because 5% of CP children have a first-degree relative with a similar condition, as yet undetermined genetic factors undoubtedly determine or at least contribute to many cases.

Several conditions mimic CP closely enough to represent diagnostic pitfalls. Several of the disorders included in this chapter cause motor impairments that physicians may mistake for CP. In addition, insidiously advancing leukoencephalopathies (see Chapter 15) may produce spastic paresis almost identical to spastic CP. Dopa-responsive dystonia gives rise to a disorder similar to choreoathetotic CP (see later and Chapter 18). Deafness, which may occur alone or be accompanied by other neurologic disabilities, may mimic CP or mental retardation.*

Neurologists often divide CP into four varieties. Each one has a characteristic motor impairment, such as spastic paresis or choreoathetosis (Fig. 13-1), and a correlation with epilepsy and mental retardation. Neurologists usually do not diagnose CP in infants until they are at least 4 months old and, in some cases, not until they are 4 years old. Moreover, once children have an established motor deficit attributable to a perinatal cerebral injury, it must not progress as the affected child grows. In fact, impairments may seem to recede as children learn compensatory strategies and benefit from various therapies.

FIGURE 13-1 Most cases of cerebral palsy (CP) are varieties of spastic CP: hemiplegic, diplegic, and quadriplegic. Because studies vary, the percentages are approximations.

Once assured that a child has a stable, congenital neurologic deficit rather than a progressive illness, neurologists concentrate on the problem at hand by evaluating the child’s disabilities and abilities in intelligence, learning, speech, and hearing as well as motor function. Because approximately 50% of children with CP have normal intelligence despite major motor deficits, neurologists do not label a child as mentally retarded without an individualized evaluation.

Although CP-induced motor impairments and associated mental retardation remain stable, comorbid epilepsy may further impair the CP child. Although epilepsy may not appear during infancy, it is usually evident before 5 years of age. Its incidence roughly corresponds to the severity of physical impairments and mental retardation (Fig. 13-2).

FIGURE 13-2 The proportion of cerebral palsy (CP) patients with mental retardation and epilepsy increases with more extensive cerebral disease. The incidence of those complications in choreoathetosis or extrapyramidal CP is only approximately 10%; however, the incidence in diplegic CP is 25%; hemiplegic CP 50%; quadriplegic CP 75%; and mixed CP 95%.

Spastic Cerebral Palsy

In spastic CP, spasticity usually impairs mobility more than paresis. It causes slow, clumsy, and stiff movements that force affected children to walk with extended, unbending legs. The spasticity also precludes them from making normal isolated movements, such as tapping one foot while keeping the other one immobile. The usual signs of upper motor neuron injury – hyperactive deep tendon reflexes, clonus, and Babinski signs – accompany the spasticity.

As a result of the cerebral injury occurring prior to physical maturation, affected limbs experience growth arrest. Arms or legs, already weak and stiff, fail to grow to their proper length and muscle structure. The thumb and great-toe nail beds are also smaller on the abnormal side. A short Achilles tendon forces children to walk on the toes of that foot.

Diplegic CP (spastic diplegia) consists of bilateral symmetric paresis characteristically involving the legs more than the arms (Fig. 13-3). This CP variety usually forces children to hold their legs straight, drawn together (adducted), and crossed over each other (“scissored”). It also forces them to keep their feet and toes pointed downward (extended). When children begin to walk, this posture obligates them to stand on their toes with their legs brought closely together.

FIGURE 13-3 A, Spastic diplegia in this 10-year-old girl with low-normal intelligence causes straightening, inturning, and adduction of her legs; a tiptoe stance; and scissor-like gait. Her uncoordinated, awkward arm movements (posturing) also reflect her cerebral palsy. B, Another patient with spastic diplegia, an 18-year-old college engineering student, has typical increased muscle tone, adduction of his legs, and “toe-walking.” He also has a subtle, sustained right-sided Babinski sign.

Neurologists usually find this variety of CP in children who have been born prematurely and have sustained periventricular leukomalacia. Because the cerebral cortex has escaped major damage, both epilepsy and mental retardation occur in a relatively small proportion (about 25%) of these children. Moreover, many of them have no cognitive impairment.

Hemiplegic CP consists of spastic hemiparesis that typically affects the face and arm more than the leg (Fig. 13-4). The motor impairment of children and adults with hemiplegic CP resembles adults with strokes from middle cerebral artery occlusions, but they differ in three respects. While normal infants younger than 2 year old do not show hand preference, infants with hemiplegic CP show premature handedness. For example, unequivocal right-handedness in infants younger than 1 year old may mean that the left hand, if not the entire left arm, is paretic. Because left hemisphere injury during the perinatal period forces the right hemisphere to assume dominance, children and adults with congenital right hemiparesis maintain dominance in the right hemisphere and have no language impairment (aphasia). Their lack of aphasia accompanying right hemiparesis contrasts starkly with the results of a left middle cerebral artery stroke, where aphasia is often the most devastating result of damage to the mature left-sided perisylvian language arc. Finally, older children and adults with hemiplegic CP show growth arrest of the affected limbs. Compared to their normal limbs, affected ones are shorter, less muscular, and weaker.

FIGURE 13-4 Hemiparetic since birth, this 28-year-old woman with normal intelligence holds her spastic and weak arm, wrist, and fingers in a flexed posture. Growth arrest of her right hand has led to shortened fingers and a less broad thumb nail bed. Similarly, her right leg, especially the heel (Achilles) tendon, is short. The growth arrest causes her to walk on her right toes and circumduct that leg. Her posture and gait are similar to that of adults after a left middle cerebral artery infarction (see Figs. 2-3 to 2-5).

Quadriplegic CP is paresis of all four limbs, usually accompanied by pseudobulbar palsy. Extensive cerebral damage, often from anoxia during delivery, usually underlies this CP variety. In contrast, cervical spinal cord birth injury causes quadriplegia without cerebral damage; however, neurologists do not include this condition within a strict definition of CP.

As a general rule, the underlying cerebral damage in quadriplegic CP is worse than in spastic hemiparesis and much worse than in spastic diplegia. Thus, epilepsy and mental retardation occur more frequently in quadriplegic than in hemiplegic CP, and occur much more frequently than in diplegic CP. Physical and occupational therapy, bracing, and orthotics may all help these children. Neurologists often reduce spasticity by recommending surgery that transposes or lengthens tendons; prescribing oral antispasticity medications, such as baclofen and tizanidine; and administering intramuscular injections of botulinum toxin (see Chapter 18). However, epilepsy in these children resists treatment. Seizure control often requires two or more antiepileptic drugs (AEDs), which in turn may produce undesirable side effects, particularly sedation, cognitive impairments, paradoxical hyperactivity, and other behavioral disturbances.

Extrapyramidal Cerebral Palsy

Involuntary writhing movements (athetosis) of the face, tongue, hands, and feet punctuated by jerking movements (chorea) of the trunk, arms, and legs – embraced by the term choreoathetosis – define extrapyramidal CP (Fig. 13-5). Although choreoathetosis may remain subtle throughout a patient’s lifetime, it often interferes with fine hand movements, walking, and even sitting. Another manifestation – involuntary larynx, pharynx, and diaphragm movements – may lead to incomprehensible dysarthria.

FIGURE 13-5 The slow sinuous movements (athetosis) of her wrists, hands, and fingers, present since age 3 years, signify that this 13-year-old girl has congenital cerebral palsy-induced choreoathetosis. The athetosis intermittently forces her hands into flexion at the wrist and her fingers into extension with overlapping positions.

Physicians should distinguish choreoathetotic CP from dopamine-responsive dystonia, which produces similar involuntary movements in young children (see Chapter 18). In short, unlike CP, dopamine-responsive dystonia is progressive (albeit slowly), fluctuating in a characteristic diurnal pattern at its onset, and, most important, responsive to small doses of levodopa (L-dopa). Despite the differences, the clinical similarity can be so great that many neurologists insist on a therapeutic trial of L-dopa before accepting a diagnosis of choreoathetotic CP.

Neurologists usually attribute choreoathetotic CP to combinations of low birth weight, anoxia, and neonatal hyperbilirubinemia damaging the basal ganglia (kernicterus). In addition, because these insults also damage the auditory pathways, hearing impairment frequently complicates the clinical picture.

Unlike spastic CP, choreoathetosis may not become clinically apparent until children are 2–4 years old. By that time, the children should have acquired steady walking and fine motor skills, but the involuntary movements have probably delayed or prevented them from acquiring these and other milestones. Similarly, hearing impairment may remain unnoticed until 1 year of age, when the rudiments of language should commence.

In contrast to the burden of these impairments, probably because kernicterus tends to spare the cerebral cortex, choreoathetotic CP is associated with a relatively low – 10% – incidence of epilepsy and mental retardation. A superficial academic or medical evaluation may underrate children with choreoathetotic CP. Despite pronounced physical impediments, many CP patients are able to complete college. Thus, both choreoathetotic and diplegic CP qualify, along with polio, ALS, and several other neurologic disorders, as physically devastating conditions that allow normal cognition.

Most systemic medications provide little relief from the choreoathetosis. Although deep-brain stimulation reduces athetosis, the procedure remains risky and is not yet perfected for this situation.

Finally, mixed-form CP – combinations of spastic paraparesis and choreoathetosis – account for about 15% of cases. They reflect the most extensive central nervous system (CNS) injury, which is naturally associated with the highest incidence of epilepsy and mental retardation – 95%.

Neural Tube Closure Defects

During the third and fourth weeks of gestation, dorsal ectoderm normally invaginates to form a closed, midline neural tube that eventually forms the brain and spinal cord and seals itself at both ends (Fig. 13-6, A). While ectoderm thus gives rise to the CNS as well as the skin, mesoderm forms the coverings of the CNS – the meninges, vertebrae, and skull.

FIGURE 13-6 Top, The neural tube forms during the third and fourth weeks of gestation. Its formation begins when the embryo’s external layer, the ectoderm, invaginates to shape a distinct, midline neural tube that eventually closes at both ends. Once closed, the embryo begins to bend into a curved fetus with the tube on the convex surface. Failure to complete this process results in defects, most commonly at the upper and lower ends of the spinal cord. Bottom left, The magnetic resonance imaging (MRI) scan shows the normal relationship of several of the structures contained in the posterior fossa: the pons (P), medulla (unmarked), cerebellum (C), and the fourth ventricle (the black, cerebrospinal fluid-filled, triangular area between the pons and middle of the cerebellum). Note that the lower portion of the cerebellum remains above the foramen magnum (indicated by a short horizontal line). Bottom right, This MRI shows an Arnold–Chiari abnormality. The lower portion of the cerebellum, which includes the tonsils, and the medulla protrude below the foramen magnum. In addition, in severe cases, aqueductal stenosis causes hydrocephalus.

The neural tube sometimes does not follow the choreography and fails to fuse at one or both of its ends. In other words, the neural tube does not close at either the prospective site of the brain or lower end of the spinal cord. The defect then expands during further embryogenesis, leading to malformations of the brain and lower spinal cord. In addition, accompanying abnormalities in the overlying meninges and either lumbosacral vertebrae or skull neural tube fail to cover neural tube closure defects. Beyond the neurologic issues, neural tube defects create some of the most heart-wrenching controversies in medicine, such as the question of whether to continue treatment of severely malformed infants and the burden of tremendous health care costs for infants with a dismal prognosis.

Upper Neural Tube Closure Defects

In an extreme example of a neural tube defect, the entire upper end of the neural tube fails to form. In this case, anencephaly, the fetus lacks a brain or has one consumed by a major malformation.

In an encephalocele, a skin-covered malformed brain, covered only by its meninges and cerebrospinal fluid (CSF), protrudes through an occipital skull defect. In a similar malformation, the Dandy–Walker syndrome, the posterior portion of the upper neural tube fails to mature. Posterior brain structures, particularly the cerebellar vermis, remain at an early embryonic stage. Expanding into the empty space, the fourth ventricle forms a large cystic structure.

A group of malformations, collectively termed the Arnold–Chiari malformation, constitute a variety of upper neural tube closure defects. Usually not obvious by external appearances, the Arnold–Chiari malformation consists of downward displacement of the lower portion of the medulla and cerebellum through the foramen magnum (Figs 13-6 and 20-22). In older children and adults, who may previously have escaped detection, this malformation may produce headaches (especially when bending), bulbar palsy, and neck pain. Patients with compression of the medulla or cerebellum require “unroofing” of the upper cervical spine and occipital portion of the skull.

In many patients, these congenital abnormalities lead to mental retardation and, because of aqueductal stenosis, obstructive hydrocephalus. Those who develop hydrocephalus typically require neurosurgical insertion of ventriculoperitoneal shunt. In addition, these upper neural tube defects are associated with comparable lower neural tube defects, such as meningomyelocele (see later).

Lower Neural Tube Closure Defects

In the most benign variety, spina bifida occulta, lumbar vertebrae simply fail to fuse. With both the underlying spinal cord and cauda equina remaining intact, this disorder usually remains asymptomatic.

In meningocele, a more serious variety, the meninges and skin protrude through a lumbosacral spine defect to form a large, CSF-filled bulge. Although this condition may remain asymptomatic, it frequently causes symptoms originating in dysfunction of the lumbar and sacral nerves, such as leg weakness, gait impairment, and bladder-emptying problems. Thus progressive hydronephrosis often complicates the deficit. Meningomyelocele (myelomeningocele), which occurs far more frequently than meningocele, is the most serious variety. It consists of a tangle of a rudimentary lower spinal cord, lumbar and sacral nerve roots, and meninges protruding into a saclike structure overlying the lumbosacral spine (Fig. 13-7). The disrupted nerve tissue causes paraparesis, areflexia, and incontinence. In addition, hydrocephalus and other brain abnormalities are comorbid in about 25% of cases. Approximately 10% of infants born with meningomyelocele die from the defect.

FIGURE 13-7 The meningomyelocele of this newborn infant has a typical broad-based, loose, translucent sac of thin, friable skin arising from the lumbar area. It contains rudiments of a spinal cord and lumbosacral nerves. Its surface weeps a mixture of serum and cerebrospinal fluid. The infant’s legs, lacking innervation, remain weak, flaccid, and areflexic. Similarly, the bladder, also lacking innervation, distends.

Meningoceles and meningomyeloceles also deprive the lower CNS of the multiple tissue barriers – intact skin, vertebrae, and meninges – that normally shield it from the environment. To prevent bacteria from entering the CSF through the defective meninges and causing meningitis, infants with meningoceles and more serious varieties must undergo neurosurgery. Therefore, neurosurgeons usually repair these defects during the infant’s first week of life not to correct the paraplegia but to prevent meningitis. Most survivors of meningomyeloceles eventually require ventricular shunting. In addition, as affected children physically mature, they often require urinary and fecal diversion procedures, revision of their ventricular shunt, and further surgery on the spine. Some neurosurgeons’ recent publications have described in utero or “prenatal” meningomyelocele surgery that reduces the risk of death and need for shunting, and may improve mental and motor function.

Causes

Some studies have implicated genetic factors. For example, the risk of a neural tube defect occurring in a sibling of an affected child is 5%. With two affected children, the risk for a third increases to 10%. Similarly, a frequent occurrence of neural tube defects in individuals with three copies of chromosome 13 (trisomy 13) or chromosome 18 (trisomy 18) suggests a genetic basis.

Other studies have attributed neural tube defects to carbamazepine and valproate, folic acid deficiency, autoantibodies to folate receptors, radiation, and various toxins, including potato blight. Although there is no complete answer, the tendency of AEDs to reduce serum folate level and thus raise homocysteine levels may explain their relationship to neural tube defects.

Prenatal testing may provide early warning of a meningomyelocele or other neural tube defect. For example, excessive concentrations of α-fetoprotein in amniotic fluid and maternal serum indicate a neural tube defect. Fetal ultrasound examination, a complementary test, may show neural tube defects as well as other congenital malformations.

Women who eat adequate amounts of fruits and vegetables, which contain folic acids and other nutrients, reduce the risk of neural tube defects by 70%. Moreover, studies have found that a folic acid intake of 5 mg daily before conception and during the first month of pregnancy reduces the incidence of neural tube defects by 85%. Based on this evidence, the US Food and Drug Administration has ordered manufacturers to add folic acid to pasta, breakfast cereals, and corn meal. In addition, neurologists avoid prescribing carbamazepine or valproate to women who are pregnant or planning to conceive.

Neurocutaneous Disorders

Embryologic defects in the ectoderm also give rise to a group of neurocutaneous disorders that consists of paired abnormalities of the brain and skin. In addition, these disorders often include abnormalities of other ectoderm and nonectoderm organs. The neurocutaneous disorders, which neurologists sometimes call the phakomatoses (Greek, phakos, lentil [bean-shaped]) allow for the quintessential diagnosis by inspection.

Most neurocutaneous disorders are inherited in an autosomal dominant pattern. Although their cutaneous component usually remains stable through adult life, the cerebral lesions sometimes undergo malignant transformation.

Tuberous Sclerosis

Tuberous sclerosis usually causes conspicuous smooth and firm nodules, facial angiofibromas (adenoma sebaceum), on the malar surface of the face (Fig. 13-8), but this illness-defining skin lesion usually fails to appear until adolescence. However, during infancy and childhood, the skin shows several other characteristics: subtle hypopigmented macules (ash-leaf spots); shagreen patches, which are leathery, scaly areas, on the lower trunk and buttocks; and periungual fibromas of the fingers.

FIGURE 13-8 Adenoma sebaceum (facial angiofibromas), the cutaneous component of tuberous sclerosis, consists of nodules several millimeters in diameter, firm, and uniformly pale. They spread over the malar surface of the face. Although adenoma sebaceum may resemble acne, acne pimples have a liquid (pus) center surrounded by inflammation. Also acne pimples accumulate on the trunk as well as the face.

The classic triad of tuberous sclerosis stigmata, which actually occurs in total in only one-third of affected children, consists of epilepsy, mental retardation, and the angiofibromas. Almost any variety of seizure may be a manifestation of the epilepsy. Refractory epilepsy, which commonly complicates the illness, portends serious mental retardation. In children with tuberous sclerosis the retardation may worsen, eventually reaching the severity of dementia. Although mental retardation and epilepsy force many children into institutions, some have a benign form that causes only minimal cognitive impairment and readily controlled epilepsy.

In another important aspect of the illness, some tuberous sclerosis children display autistic behavior. Thus, neurologists consider tuberous sclerosis as one of several neurologic causes of autism-like symptoms (Box 13-1).

Box 13-1

Neurologic Syndromes that Include Autism-Like Symptoms

The CNS counterpart of the skin lesions consists of cerebral tubers that are potato-like brain nodules, 1–3 cm in diameter. The tubers frequently grow to compress and irritate the surrounding cerebral cortex, thus producing the epilepsy and progressive cognitive impairment. Although usually benign, tubers sometimes undergo malignant transformation. In addition, retinal, renal, and cardiac tumors develop.

Especially because tubers tend to calcify, computed tomography (CT) and sometimes even plain skull X-rays identify them; however, magnetic resonance imaging (MRI) is the better test to detect and monitor tubers. Removing the tubers may reduce intracranial pressure, relieve obstructive hydrocephalus, excise a malignancy, and reduce seizure frequency, but neurosurgery is usually not feasible when tubers are numerous and deeply situated. Emerging forms of chemotherapy include everolimus, which inhibits a gene product and thus reduces the size of the tubers.

The majority of tuberous sclerosis cases (70%) occur spontaneously. Nevertheless, whether inherited in autosomal dominant pattern or arising sporadically, the disorder is attributable to mutations in either of two tumor suppressor genes: tuberous sclerosis complex (TSC 1) on chromosome 9, and TSC 2 on chromosome 16.

Neurofibromatosis

Commonly occurring neurofibromatosis, neurofibromatosis type 1 (NF1) – previously called von Recklinghausen disease or “peripheral-type” neurofibromatosis – also causes a clinical triad: multiple café-au-lait spots, neurofibromas, and Lisch nodules.

Café-au-lait spots, the signature of neurofibromatosis, are areas of uniformly light brown, oval, and flat skin (Fig. 13-9). Although individual café-au-lait spots are found in at least 10% of normal individuals, the presence of more than six of them, each larger than 5 mm in children and 1.5 cm in adults, strongly suggests a diagnosis of neurofibromatosis. Freckling in the axilla and groin – two skin surfaces sheltered from sun exposure – often accompanies NF1-related café-au-lait spots.

FIGURE 13-9 Café-au-lait spots are flat, light-brown skin lesions. The diagnosis of neurofibromatosis requires six or more lesions, each measuring at least 1.5 cm in adults and 0.5 cm in children.

Neurofibromas consist of soft, palpable, subcutaneous growths, each a few millimeters to several centimeters in size, that emerge along peripheral nerves (Figs 13-10 and 13-11). They can also grow from nerve roots within the spinal canal and compress the spinal cord or cauda equina. They occasionally reach grotesque proportions or induce extraordinary growth of an affected limb. However, the famous nineteenth-century “elephant man,” Joseph Merrick, commonly cited as an example of neurofibromatosis, probably suffered from a related condition, Proteus syndrome.

FIGURE 13-10 Neurofibromas often grow to several centimeters of disfiguring protuberances on the face.

FIGURE 13-11 Neurofibromas are often subtle, multiple, subcutaneous, soft, and typically less than 0.5 cm in size.

Lisch nodules, the least obvious but most common manifestation, are multiple, asymptomatic, macroscopic, yellow to brown nodules (melanocytic hamartomas) situated on the iris (Fig. 13-12). Although a slit-lamp examination may be required to detect Lisch nodules and then differentiate them from inconsequential pigment collections, they are almost pathognomonic of the disorder.

FIGURE 13-12 Lisch nodules, virtually pathognomonic of neurofibromatosis type 1, are pigmented aggregations on the iris that are often visible with the unaided eye.

Excision of neurofibromas, except for those compressing the spinal cord or other vital structures, is impractical because NF1 involves innumerable peripheral nerves. However, laser therapy can blanch café-au-lait spots.

Although its cutaneous manifestations probably represent the most conspicuous sign of any neurocutaneous disorder, NF1 is not entirely peripheral. As with other disorders in this group, NF1 induces intracerebral tumors, particularly optic nerve gliomas, as well as intraspinal neurofibromas.

NF1 has a close association with attention deficit hyperactivity disorder (ADHD) and learning disabilities. Some tests detect sustained attention difficulties and learning disabilities in the majority of NF1 children. The IQ of NF1 children is about 5–10 points lower than average.

Despite those comorbidities, NF1 children and adults do not greatly differ from the general population. Only 4–8% are mentally retarded and psychosis occurs at no greater frequency than in the general population. Moreover, unlike the increased prevalence of autistic behavior in tuberous sclerosis, such behavior is not associated with either variety of NF.

Approximately 50% of patients inherit NF1 in an autosomal dominant pattern, usually because of a gene situated on chromosome 17. In the remainder of patients, NF1 arises sporadically. (The mnemonic for recalling the abnormal chromosome is “von Recklinghausen contains 17 letters.”) The incidence of NF1, like Down syndrome, increases with advanced paternal age.

Neurofibromatosis type 2 (NF2), which occurs only 10% as frequently as NF1, is an almost completely different disorder. NF2, also called familial acoustic neuroma or “central-type” neurofibromatosis, is characterized by bilateral acoustic neuromas (vestibular schwannomas) that steadily impair hearing until deafness ensues. It may induce a few neurofibromas and large, pale café-au-lait spots, but its hallmark remains the acoustic neuromas (see Fig. 20-27). In fact, NF2 is usually unrecognized until acoustic neuromas are discovered.

This neurocutaneous disorder is associated with two neoplastic complications, acoustic neuroma and meningiomas. Gadolinium-enhanced MRIs can readily show these complications. Although neurosurgeons can remove acoustic neuroma, sometimes they must sacrifice the adjacent acoustic nerve. Alternatively, pinpoint radiation or laser treatment may be able to burn away the tumor while sparing both nerves.

Unlike NF1, NF2 does not cause behavioral, learning, or cognitive impairments. Also, NF2 is inherited on chromosome 22 and, in the vast majority of cases, in an autosomal dominant pattern. (The mnemonic for its inheritance is “Chromosome 22 carries the NF2 mutation.”)

Sturge–Weber Syndrome

Sturge–Weber syndrome, also known as encephalo–trigeminal angiomatosis, consists simply of angioma of both the face (nevus flammeus) and underlying cerebral hemisphere. Unlike other neurocutaneous disorders, Sturge–Weber syndrome is an embryonal developmental disorder rather than a genetic disorder. Thus, it appears sporadically and does not strike multiple family members.

The facial angioma consists of a deep red discoloration (“port-wine stain”) in the distribution of one or more divisions of the trigeminal nerve (Fig. 13-13). Its extent does not correlate with the size of the cerebral abnormality. Clinicians must distinguish it from completely benign, more common skin abnormalities, such as small forehead angiomas (“strawberry nevi”). Also, port-wine stains, even in the trigeminal nerve distribution, are associated with Sturge–Weber syndrome in only 8% of cases. Whether or not facial angiomas are a manifestation of Sturge–Weber syndrome, laser therapy can bleach them.