Diseases of the Brain and Meninges

Suddenly Speechless

A 59-year-old manager of an information technology firm, previously in good health, suddenly felt unwell late one afternoon at work, with a warm feeling in his head that was hard to describe. He slowly cleared his desk and drove home. On arrival, he could not carry on a conversation with his wife: he understood her easily but found no words to answer her. He went to bed and slept for 2 hours, but still could not speak properly on awakening. He went to the emergency room of the nearest hospital. The neurologic examination there, 4 hours after the onset of symptoms, revealed aphasia with word-finding difficulty and paraphasic errors, as well as a mild right central facial palsy. His blood pressure was 165/95 mm Hg.

The mainly motor aphasia and the right facial palsy implied a left frontal disturbance, and the acute onset was consistent with cerebral ischemia or hemorrhage as the most likely cause. To pin down the diagnosis, a computed tomography (CT) scan was performed immediately after the examination. It showed hypodensity in the left insular cortex, most likely representing an ischemic stroke. Occlusion of a major cerebral vessel was ruled out by duplex ultrasonography. As the patient had not presented to the emergency room until 4 hours after the onset of symptoms, and the clinical and neuroradiologic workup had taken an additional 35 minutes, the temporal window for intravenous thrombolysis was already over. A magnetic resonance imaging (MRI) scan confirmed the diagnosis of a territorial ischemic stroke: the lesion was hyperintense on both the diffusion-weighted image and the T2-weighted spin-echo image. Given that occlusion of a major cerebral vessel had been ruled out, endovascular recanalization was not indicated. The need remained to find the cause of the stroke to protect the patient from further such events.

His family physician had measured mildly elevated blood pressure values at various times in the past, and he had been mildly overweight for several years, with a high cholesterol level. He had also complained of bothersome palpitations on multiple occasions over the past few months. A 24-hour electrocardiogram (ECG) showed intermittent atrial fibrillation; echocardiography revealed no other cardiac abnormality.

The most likely cause of the stroke was atrial fibrillation leading to clot formation in the left atrium and then embolism of a blood clot into the brain (cardioembolic stroke). Oral anticoagulation was begun to prevent further clot formation in the left atrium. This measure lowers the risk of a second stroke by two-thirds. An antihypertensive drug and a statin were also prescribed, and the patient was encouraged to lose weight by means of a healthier diet and regular physical exercise. His aphasia improved markedly during his hospital stay; only mild word-finding difficulty remained when he was discharged.

6.1 Congenital and Perinatally Acquired Diseases of the Brain

Key Point

The main types of brain disease that are congenitally present or acquired at the time of birth are the following: cerebral movement disorders of perinatal origin (infantile cerebral palsy), developmental disorders of the neural tube (dysrhaphias), childhood hydrocephalus, heterotopias (islands of gray matter in the brain at abnormal locations outside the cerebral cortex), combined disease of the brain and skin (phakomatoses), malformations of the skull, and infections that are acquired in utero.

6.1.1 Fundamentals

▶ Table 6.1 contains an overview of the major types of brain damage that are present at birth, or acquired in early childhood, and their causes. The most common ones are:

Genetic disorders.
Disorders acquired during intrauterine life: infections (rubella embryopathy, toxoplasmosis, cytomegalovirus [CMV], syphilis, human immunodeficiency virus [HIV]) and chronic intoxications (alcohol embryopathy).
Complications of delivery (cerebral hypoxia during birth, birth trauma).

Prematurity and difficult delivery are the most important risk factors.

**Table 6.1** Important causes of congenital and perinatally acquired brain damage
Cause	Examples
Perinatal asphyxia
Structural anomalies of the brain	Microcephaly Meningoencephalocele (cf. ▶ Fig. 6.3a) Meningomyelocele Micropolygyria Arnold–Chiari malformation (cf. ▶ Fig. 6.3b) Dandy–Walker syndrome with or without hydrocephalus
Phakomatoses	Tuberous sclerosis (Bourneville disease) Encephalofacial angiomatosis (Sturge–Weber disease) Neurofibromatosis, type 1 (von Recklinghausen disease) and type 2 von Hippel–Lindau disease Ataxia telangiectasia (Louis–Bar syndrome)
Brain damage acquired in utero	Rubella embryopathy Congenital toxoplasmosis Congenital cytomegaly Congenital syphilis Congenital HIV infection Alcohol embryopathy
Rh incompatibility	Severe neonatal jaundice
Synostosis and craniostenosis (see ▶ Fig. 6.6)
Traumatic intracranial hemorrhage during delivery	Subdural hematoma Intracerebral hemorrhage Intraventricular hemorrhage

6.1.2 Cerebral Movement Disorders

Multiple mechanisms of injury to the developing brain (cf. ▶ Table 6.1) can cause movement disorders of varying degrees of severity; these are known collectively as cerebral movement disorders or infantile cerebral palsy.

Clinical features The manifestations of cerebral movement disorder include:

Disturbances of movement of many different kinds; the more common ones are summarized in ▶ Table 6.2. These are usually accompanied by a variably severe delay of motor development.
Intellectual disability (sometimes designated “childhood psycho-organic syndrome” or “attention deficit–hyperactivity syndrome”) is common and is characterized by the delayed acquisition of mental abilities, impaired attention, and often also hyperactivity and inability to concentrate.
Epileptic seizures often arise later on.

Practical Tip

The term psychomotor retardation refers to a combination of movement disturbances and intellectual disability.

**Table 6.2** The most important cerebral movement disorders
Disorder	Clinical features	Pathoanatomic substrate	Causes
Infantile spastic diplegia (Little disease)	Spasticity, predominantly in the legs; pes equinus, scissor gait, mentally often normal	Pachymicrogyria (abnormally hard, small gyri)	Perinatal injury (disturbance of cerebral development, embryopathy, severe neonatal jaundice)
Congenital cerebral monoparesis	Usually paresis of arm and face	Porencephaly (cavities in the brain parenchyma), localized atrophy	Birth trauma (asphyxia, hemorrhage)
Congenital hemiparesis	Arms more severely affected than legs, seizures in ~50%, usually mentally impaired	Porencephaly	Birth trauma (asphyxia, hemorrhage)
Congenital quadriparesis (bilateral hemiparesis)	Arms more severely affected than legs, occasionally bulbar signs, seizures; severe mental impairment	Porencephaly, bilateral; often hydrocephalus	Birth trauma (asphyxia, hemorrhage), also prenatal injury
Congenital pseudobulbar palsy	Dysphagia to liquids, dysarthria, usually not mentally impaired	Bilateral lesions of the corticobulbar pathways	Prenatal injury or birth trauma, congenital malformation (syringobulbia)
Bilateral athetosis (athétose double) and congenital chorea (choreoathetosis)	Athetotic or other involuntary movements, often combined with spastic paresis	Basal ganglionic defects, status marmoratus (multiple confluent gliotic areas in the basal ganglia); status dysmyelinisatus (Vogt) in cases of later onset	Disturbances of cerebral development, perinatal injury, especially severe neonatal jaundice
Congenital rigor	Rigor without involuntary movements, postural abnormalities, no pyramidal tract signs, severe mental impairment, seizures	Status marmoratus	Disturbances of cerebral development, perinatal injury, especially severe neonatal jaundice
Congenital cerebellar ataxia	Gait ataxia, intention tremor and impaired coordination, motor developmental retardation, dysarthria, sometimes in combination with other motor syndromes	Cerebellar developmental anomalies	Disturbances of cerebellar development