83

6Diseases of the Brain and Meninges

Congenital and Perinatally Acquired Diseases				Infectious Diseases of the Brain and Meninges . . .			111
of the Brain . . .	83			Metabolic Disorders and Systemic Illnesses
Traumatic Brain Injury . . .		87		Affecting the Nervous System		. . . 120
Intracranial Pressure and Brain Tumors . . .			92	Diseases of the Basal Ganglia . . .		127
Circulatory Disorders of the Brain and				Cerebellar Diseases . . .	135
Nontraumatic Intracranial Hemorrhage			. . . 98	Dementing Diseases . .	. 137

Congenital and Perinatally Acquired Diseases of the Brain

Fundamentals

	The developing brain is vulnerable to damage by a		Disturbances of movement of many different
	number of different pathological mechanisms. The		kinds; the more common ones are summarized
	variably severe neurological deficits that result are		in Table 6.1. These are usually accompanied by a
	known collectively as cerebral movement dis-		variably severe delay of motor development.
	orders or infantile cerebral palsy (CP). In general,		Mental retardation (sometimes designated
	this term implies the presence of deficits of multi-		“childhood psycho-organic syndrome”) is com-
	ple types:		mon and is characterized by the delayed acqui-

Table 6.1 The most important cerebral movement disorders

Name of disorder	Clinical features	Pathoanatomical substrate	Causes
infantile spastic	spasticity, predominantly in the legs;	pachymicrogyria (abnormally	perinatal injury (disturbance
diplegia	pes equinus, scissor gait, mentally	hard, small gyri)	of cerebral development,
(Little disease)	often normal		embryopathy, severe neonatal
			jaundice)
congenital cerebral	usually, paresis of arm and face	porencephaly (cavities in the	birth trauma (asphyxia,
monoparesis		brain parenchyma), localized	hemorrhage)
		atrophy
congenital	arms more severely affected than	porencephaly	birth trauma (asphyxia,
hemiparesis	legs, seizures in ca. 50 %, usually		hemorrhage)
	mentally impaired
congenital quadri-	arms more severely affected than	porencephaly, bilateral;	birth trauma (asphyxia,
paresis (bilateral	legs, occasionally bulbar signs,	often hydrocephalus	hemorrhage), also prenatal
hemiparesis)	seizures; severe mental impairment		injury
congenital pseudo-	dysphagia to liquids, dysarthria,	bilateral lesions of the	prenatal injury or birth
bulbar palsy	usually not mentally impaired	corticobulbar pathways	trauma, congenital malforma-
			tion (syringobulbia)
atonic−astatic	generalized flaccid weakness, inabil-	frontal lobe atrophy cerebellar
syndrome (Foerster)	ity to stand, impaired coordination,	defects
	severe mental impairment
bilateral athetosis	athetotic or other involuntary move-	basal ganglionic defects, status	disturbances of cerebral
(athétose double) and	ments, often combined with spastic	marmoratus (multiple confluent	development, perinatal injury,
congenital chorea	paresis	gliotic areas in the basal ganglia);	esp. severe neonatal jaundice
(choreoathetosis)		status dysmyelinisatus (Vogt) in
		cases of later onset
congenital rigor	rigor without involuntary move-	status marmoratus	disturbances of cerebral
	ments, postural abnormalities, no		development, perinatal injury,
	pyramidal tract signs, severe mental		esp. severe neonatal jaundice
	impairment, seizures
congenital cerebellar	gait ataxia, intention tremor and	cerebellar developmental	disturbances of cerebellar
ataxia	impaired coordination, motor	anomalies	development
	developmental retardation, dys-
	arthria, possibly in combination with
	other motor syndromes

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6

Diseases of the Brain and Meninges

84 6 Diseases of the Brain and Meninges

		seizures), and certain symptoms may worsen over the
sition of mental abilities, by impaired attention,
		course of the individual’s life.
and often also by hyperactivity and inability to
concentrate. The term psychomotor retardation
refers to a combination of movement distur-		Special Clinical Forms
bances and mental retardation.
Epileptic seizures often arise later on.		Some of the more important etiological types of early
Common types and their causes. Tables 6.1, 6.2 pro-		childhood brain damage will now be discussed in-
		dividually:
vide an overview of the major types of brain damage
that are present at birth, or acquired in early childhood,		Hydrocephalus is a pathological dilatation of the inner
and their causes. These include genetic disorders, cere-		(and sometimes also the outer) cerebrospinal fluid
bral hypoxia during the birth process, birth trauma, in-		spaces. Various types of hydrocephalus are listed in
trauterine infections (rubella embryopathy, toxoplas-		Table 6.3. In terms of pathogenesis, the most common
mosis, cytomegalovirus, syphilis, HIV), and chronic in-		type of hydrocephalus in childhood is occlusive hydro-
toxications (alcohol embryopathy). Prematurity and dif-		cephalus (gliosis, stenosis, or malformation of the aque-
ficult delivery are the most important risk factors.
Possible indications of brain damage in the newborn
include cyanosis at birth, a weak cry, and hypotonia. In
the early prenatal period, there may be further abnor-
malities of muscle tone, as well as pathological reflexes
(cf. p. 43 ff.). Later on, a squint or left-handedness may
be a sign of brain damage.
Treatment consists of physical therapy (e. g., of the
Bobath or Vojta type), which should be begun as early as
possible, making use of the child’s reflex behavior, as
well as special education and rehabilitation. The goal of
treatment is maximal independence.
Prognosis. Although the neurological deficits of cere-
bral palsy do not progress over time, certain manifesta-
tions may not appear until later in life (e. g., epileptic

Table 6.2 Important causes of congenital and perinatally acquired brain damage

Perinatal asphyxia

(Genetically determined) structural anomalies of the brain, e.g.:

microcephaly

meningoencephalocele

meningomyelocele

micropolygyria

Arnold−Chiari malformation, with or without hydrocephalus

Phakomatoses

tuberous sclerosis (Bourneville disease)

encephalofacial angiomatosis (Sturge−Weber disease)

neurofibromatosis (von Recklinghausen disease)

von Hippel−Lindau disease

Brain damage acquired in utero

rubella embryopathy

congenital toxoplasmosis

congenital cytomegaly

congenital syphilis

congenital HIV infection

alcohol embryopathy

Severe neonatal jaundice (due to Rh incompatibility)

Synostosis and craniostenosis

Traumatic intracranial hemorrhage during delivery

subdural hematoma

intracerebral hemorrhage

intraventricular hemorrhage

Fig. 6.1 Arnold−Chiari malformation (MR image). The cerebellar tonsils are caudally displaced below the arch of the atlas deep into the cervical spinal canal (courtesy of Dr. D. Huber, Radiological Institute, Hirslanden−Klinik, Zurich).

Table 6.3 Types and terminology of hydrocephalus

Internal	enlargement of the ventricles:
hydrocephalus
obstructive	due to obstruction of CSF flow within the
	ventricular system (e. g., aqueductal stenosis)
	or at its exits (e. g., obstruction of foramina
communicat-	of Magendie and Luschka)
	nonobstructive internal hydrocephalus
ing
malabsorptive	a subtype of communicating hydrocephalus
	due to impaired CSF resorption (e. g., cister-
	nal adhesions or dysfunction of the pacchion-
	ian granulations)
External	enlargement of the subarachnoid space over
hydrocephalus	the cerebral convexities and/or in the cisterns
External and	combination of the above
internal
hydrocephalus
Hydrocephalus	internal and external hydrocephalus second-
ex vacuo	ary to brain atrophy

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Congenital and Perinatally Acquired Diseases of the Brain

duct, Arnold−Chiari malformation [Fig. 6.1] with impaired outflow through the foramina of Luschka and Magendie). In the Arnold−Chiari malformation, part of the medulla and the cerebellar tonsils are displaced below the foramen magnum into the cervical spinal canal. This anomaly may be combined with internal hydrocephalus and syringomyelia.

There may also be communicating hydrocephalus, whose etiology and pathogenesis are often unclear.

The chief clinical sign of hydrocephalus in childhood is abnormal enlargement of the head, which may already be noted in a prenatal ultrasound study or at birth, and which progresses over time. Protrusion of the frontal bone and depression of the orbital plate make the upper part of the sclera visible and cause the lower part of the iris to sink below the lower lid, in the so-called “settingsun sign.” The essential diagnostic tests are CT and/or MRI. The treatment, if required, is neurosurgical, usually the implantation of a ventriculoperitoneal or ventriculoatrial shunt. The prognosis of isolated hydrocephalus, in the absence of other neurological abnormalities, is good: once the hydrocephalus is treated, two-thirds of children go on to have a normal physical and mental development.

Microcephaly is usually due to prenatal toxic influences

(e. g., alcohol) or infections (e. g., cytomegalovirus), or to genetic factors. Affected persons are generally of lower than normal intelligence.

Dysraphic malformations. The most common type is spina bifida with meningomyelocele: in this disorder, there is a closure defect of the posterior arches of multiple vertebrae, usually in the lumbosacral region, accompanied by a prolapse of the meninges and spinal cord through the defect. The level and extent of spinal cord involvement determine whether paralysis of the lower limbs will be manifest at birth. Even if the defect is surgically repaired in the first few hours after birth, major sensorimotor impairment and urinary disturbances generally persist. This type of malformation may be accompanied by internal hydrocephalus and by anomalies of the craniocervical junction, which often require treatment. Other dysraphic syndromes include acrania (partial or total absence of the skull), anencephaly (absence or degeneration of most of the brain, with acrania— practically always a fatal condition), and encephalocele (prolapse of the meninges and brain tissue through a defect in the bony skull).

Areas of neuronal heterotopia (i. e., islands of gray matter anomalously lying outside the cerebral cortex) may be found in the periventricular zones or in a subcortical layer (lamina) that creates the appearance of a “double cortex” on MRI. Subcortical laminar heterotopia

(SCLH) is a genetic disorder of dominant inheritance caused by a mutation of the doublecortin gene on the X chromosome. The disorder is more severe, and often lethal, in males, because they lack a normal copy of the gene. In surviving males, SCLH is often combined with lissencephaly (“smooth brain,” i. e., absence of the cerebral gyri and sulci). Heterotopia is a common cause of epilepsy.

Ulegyria is a type of early childhood brain damage characterized by scarring and abnormally small gyri (microgyria). These structural abnormalities can be seen on MRI.

Phakomatoses are genetic disorders that cause complex malformations and tumors predominantly affecting the ectodermally derived structures of the body, i. e., the brain, peripheral nervous system, and skin. They are also called neurocutaneous disorders. The internal organs may also be affected. An overview is provided in Table 6.4.

The main types of brain disorder acquired in utero are the following:

Rubella embryopathy occurs in 10 % of infants that have been exposed by maternal infection in the first trimester of pregnancy. The associated anomalies include cataracts, deafness, microcephaly, and heart defects.

Congenital toxoplasmosis occurs when the fetus is infected in the second half of gestation by maternal infection in a mother without previous exposure to Toxoplasma gondii. Its manifestations include psychomotor retardation, convulsions, progressive hydrocephalus, and visual disturbances due to chorioretinitis. Plain radiographs and CT reveal intracerebral calcifications.

Congenital cytomegalovirus infection causes premature birth and low birth weight, microcephaly, hydrocephalus, convulsions, periventricular calcifications, and abnormalities in organs outside the nervous system as well.

Congenital HIV infection occurs in one-quarter of all babies born to HIV-positive mothers. It causes encephalopathy with psychomotor retardation, as well as immune deficiency, with later complications.

Congenital syphilis is now rare. Its typical stigmata include a saddle nose, cutaneous fissures at the corners of the mouth, and later crescentic defects of the teeth (Hutchinson teeth), interstitial keratitis, and hearing loss.

Malformations of the skull come in many different forms: there are dysraphic malformations characterized by faulty closure of the cranial vault (cranioschisis), premature closure of the cranial sutures (craniostenosis), and anomalies of the craniocervical junction including basilar impression, platybasia, Arnold−Chiari syndrome (p. 84), and Dandy−Walker syndrome (malformation of the posterior fossa with aplasia of the inferior portion of the cerebellar vermis, cystic enlargement of the fourth ventricle, and occlusive hydrocephalus). The more common types of craniosynostosis are listed and illustrated in Table 6.5.

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Diseases of the Brain and Meninges

86	6 Diseases of the Brain and Meninges
		Table 6.4 The most important phakomatoses
		Disease	Neuropathology and	Further features	Age of onset and other
			clinical neurological manifestations		remarks
		tuberous sclerosis	glial tumors (giant cell astrocy-	multiple (fibro-)adenomas in the	salaam seizures often appear
		(Bourneville disease)	tomas, “tubers”) in the ventricular	face (typically butterfly-shaped,	as early as infancy; autosomal
			walls and surface of the brain, often	adenoma sebaceum) as well as	dominant inheritance
			calcified; as a result, thickening and	on the gums and nails; adenomas
			sclerosis of the gyri of the cerebral	in the heart, kidney, and retina
			and cerebellar cortex. Clinical

manifestations: mental retardation, epileptic seizures

encephalofacial	calcified, mixed capillary and venous
angiomatosis	angioma of the leptomeninges,
(Sturge−Weber	usually unilateral, with reactive atro-
disease)	phy and gliosis of the neighboring
	brain parenchyma; serpentine in-
	tracranial calcification is a typical
	radiograph finding. Possible clinical
	manifestations: epileptic seizures,
	mental retardation, and sometimes
	hemiparesis

choroidal hemangioma and angioma of the face (nevus flammeus) on the same side as the intracranial lesion

onset in early childhood; sporadic or dominant inheritance pattern, with variable penetrance

von Hippel−Lindau	cystic hemangioblastoma, usually in
disease	a cerebellar hemisphere, causing pro-
	gressive cerebellar signs and signs of
	intracranial hypertension
neurofibromatosis	multiple neurofibromas of periph-
(von Recklinghausen	eral nerves, nerve roots (particularly
disease)	in the cauda equina) and cranial
	nerves;
	intracranially, in some cases, bi-
	lateral acoustic neuroma and/or
	meningioma (in neurofibromatosis
	type II), or optic glioma and/or
	astrocytoma (type I); clinically, pro-
	gressive radicular or peripheral
	nerve deficits (flaccid paresis,
	sensory deficits), signs and symp-
	toms of a cerebellopontine angle
	tumor (esp. hearing loss, tinnitus),
	visual impairment with optic glioma

retinal angiomatosis; less commonly, cystic changes of other internal organs (esp. kidney, pancreas, epididymis)

variable number and density of nodular skin lesions, which may be either broad-based or pedunculated (cutaneous neurofibroma); café-au-lait spots

onset in middle age; autosomal dominant inheritance

the cutaneous changes are often present at birth or become apparent in early childhood; they typically become very prominent in puberty. Malignant degeneration is possible. Autosomal dominant inheritance, with frequent new mutations

Table 6.5 Types of craniosynostosis

Type	Fused suture	Shape of head	Remarks
scaphocephaly	sagittal suture	long, narrow (“boat-shaped”)
(=dolichocephaly)
			most common form
acrocephaly	coronal suture	high, broad on top;
		flat forehead

oxycephaly	sagittal, coronal,	pointed
	and lambdoid sutures

second most common form

brachycephaly coronal and lambdoid sutures short, broad

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