Diseases of the Basal Ganglia

Clinical manifestations include:

paucity of movement,

gait disturbance early in the course of the disease,

predominantly axial rigidity,

often, a permanently extended cervical spine (head turned upward),

frequent falls,

tendency to fall backward,

progressive dementia,

an impairment of vertical gaze movements (particularly downward), with nystagmus.

Course. This disease presents between ages 50 and 70, mainly in men. It progresses rapidly and causes death within a few years.

Multiple System Atrophies (MSA)

This term subsumes a variety of rare diseases that have also been described individually: olivo-ponto-cerebellar atrophy (OPCA), striatonigral degeneration (SND), Shy− Drager syndrome (SDS), and mixed forms of these.

The neuropathological lesion consists of cellular degeneration and gliosis in the substantia nigra, striatum, pons, inferior olive, and cerebellum.

Treatment of MSA is generally not very effective, though dopamine agonists tend to be more effective than L-DOPA. The disease usually leads to severe disability within a few years of onset.

Corticobasal Degeneration

Neuropathological lesion of this disease consists of cellular degeneration and gliosis in the substantia nigra and in the precentral and postcentral gyri. The cerebral peduncles are correspondingly diminished in size.

Clinical manifestations , which are asymmetrically distributed, include:

impaired fine motor control of an arm (early in the course of the disease),

progressive rigidity and akinesia,

weakness,

central sensory disturbances,

(sometimes) apraxia,

(sometimes) dystonia.

Treatment with L-DOPA is generally not very effective and patients usually become severely disabled within a few years of the onset of the disease.

The main clinical manifestations are present to varying extents in the different forms of MSA, each of which has its own characteristic initial presentation:

bradykinesia, akinesia, rigidity, and rest tremor (seen early in the course of OPCA and SND),

autonomic dysfunction, including orthostatic hypotension, incontinence, and impotence in men (seen early in the course of SDS),

ataxia and other cerebellar signs (prominent in OPCA),

pyramidal tract signs.

The diagnosis is made from the clinical manifestations. Other findings that are compatible with the diagnosis of MSA may include partial brain atrophy, as revealed by MRI, or a reduction of glucose metabolism or of the concentration of dopamine receptors in the striatum, as revealed by PET or SPECT.

Lewy Body Disease

This disease is described below on p. 139.

Diseases Causing Hyperkinesia

These diseases, unlike Parkinson disease, cause “too much” movement, often in combination with diminished muscle tone. The different clinical varieties of hyperkinesia include chorea, athetosis,ballism and dystonia, and mixed forms. Each of these disturbances of movement may be due to many different causes. The hyperkinetic extrapyramidal diseases are a heterogeneous group with regard to both phenomenology and etiology.

Table 6.26 provides an overview of the extrapyramidal diseases that manifest themselves as hyperkinetic syndromes. The more important members of this group are described in greater detail in this section.

131

6

Diseases of the Brain and Meninges

Table 6.26 The diagnostic evaluation of hyperkinetic extrapyramidal syndromes

Syndrome	Features	Etiology	Remarks
Chorea
Chorea minor	sudden, usually rapid, distal, brief,	autoimmune; streptococcal	often a sequela of streptococcal pha-
	irregular involuntary movements;	infection	ryngitis, most commonly in girls
	hypotonia		aged 6−13 years
Chorea mollis		autoimmune; streptococcal	hypotonia is prominent
		infection
Chorea gravidarum		3rd−5th month of pregnancy	usually during first pregnancy, often
			with prior history of chorea minor
Chorea due to an-			rare, reversible with discontinuation
tiovulatory agents			of the drug
			Continued

blubber blubber

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132	6 Diseases of the Brain and Meninges
		Table 6.26 The diagnostic evaluation of hyperkinetic extrapyramidal syndromes (Continued)
		Syndrome	Features	Etiology	Remarks
		Huntington		autosomal dominant inheri-	onset usually at age 30 to 50; associated
		disease		tance	with progressive dementia
		Benign familial		autosomal dominant inheri-	onset in childhood, no further progres-
		chorea		tance	sion, no dementia
	Choreoacantho-			autosomal recessive	mainly orofacial, tongue-biting, elevated
	cytosis				CPK, hyporeflexia, acanthocytosis
	Postapoplectic			vascular (prior stroke)	sudden hemichorea and hemiparesis, of-
	chorea				ten combined with hemiballism
	Senile chorea			vascular and degenerative	occasional presenile onset, often more se-
					vere on one side, occasionally with de-
					mentia
	Athetosis
	Status marmoratus		Slow, exaggerated movements	perinatal asphyxia	soon after birth, increasingly severe athe-
			against resistance of antagonist		totic hyperkinesia, often cognitive impair-
			muscles, predominantly distal, ap-		ment, sometimes also spasticity
			pear uncomfortable and cramped

Status dysmyelinisatus

Pantothene kinasejoint hyperflexion/hyperextension associated neuro-

degeneration (formerly called Hallervorden−Spatz disease)

Hemiathetosis

Ballism/Hemi-	unilateral, lightning-like, high-
ballism	amplitude flinging movements of
	multiple limb segments
Dystonic
syndromes
Torsion dystonia	slow, tonic contractions of mus-
	cles or muscle groups, of shorter
	or longer duration, usually against
	the resistance of antagonist mus-
	cles
Spasmodic	slow contraction of cervical and
torticollis	nuchal musculature against anta-
	gonist resistance, with turning
	movements of the head
Localized dystonia	see text, p. 134

kernicterus of the newborn

autosomal recessive disorder of pigment metabolism

focal lesion of pallidum and striatum

ischemic or neoplastic lesion of the subthalamic nucleus

familial syndromes

symptomatic types

idiopathic, occasionally after cervical spine trauma and various other causes

present at birth, often with other signs of perinatal brain damage; further progression

choreoathetotic movements beginning at age 5−15 years, rigidity, dementia, and retinitis pigmentosa in one-third of cases; progressive, death by age 30

unilateral, may come about some time after the causative lesion

sudden onset, usually with hemiparesis as well

often in families of Jewish ancestry, onset in the 1st−2nd decade of life with focal dystonia, later rotating movements of head, trunk, and limbs, as well as athetotic movements of the fingers

e. g., in Wilson disease, Huntington disease, pantetheine kinase-associated neurodegeneration

one-third spontaneous recovery, one-third no change, one-third progression to torsion dystonia

e. g., writer’s cramp, faciobuccolingual dystonia, oromandibular dystonia

Diseases Causing Chorea

The neuropathological basis of chorea consists of degeneration of small neurons, mainly in the putamen and caudate nucleus. This lesion is particularly evident in hereditary chorea (see below).

Clinical manifestations. Chorea consists of irregular, sudden, involuntary movements that are usually more pronounced at the distal end of the limbs. In some patients, these movements are of low amplitude and look almost normal, resembling nonpathological “fidgetiness”; in others, they are massive and highly disturbing. They can appear on one side (“hemichorea”) or

both (Fig. 6.34). The muscle tone is normal or diminished, there is no weakness or sensory deficit, and pyramidal tract signs are absent. The intrinsic muscle reflexes are normal, except that they may have a second extension phase (Gordon phenomenon) if elicited at the same time as an incipient choreiform movement. Choreiform movements, like other types of hyperkinetic movement (see below), are typically enhanced by goaldirected movement, mental stress, or concentration, and subside in sleep and under general anesthesia.

Individual etiologic forms. Chorea has diverse causes and the prognosis depends on the cause.

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Diseases of the Basal Ganglia 133

Fig. 6.34 Senile hemichorea. Drawings made from a film recording.

Huntington disease (chorea major) is a genetic disorder of autosomal dominant inheritance due to an unstable CAG trinucleotide repeat expansion on chromosome 4. The clinical manifestations generally arise between the ages of 30 and 50 (earlier in patients who inherited the defective gene from their father). Rigidity and pyramidal tract signs are sometimes present at the outset, but, as a rule, choreiform movements soon dominate the clinical picture, accompanied by progressive dementia. The disease progresses chronically, generally ending in death 10 to 15 years after the onset of symptoms. There is no treatment other than palliative, symptomatic management (see below).

Chorea minor (Sydenham chorea) is the most common etiologic form of chorea. It mainly strikes school-aged girls after an infection with -hemolytic group A streptococci and is caused by an autoimmune reaction in which antibodies are generated that cross-react with neurons. Within a few days or weeks after an attack of “strep throat,” or within a few weeks or months of an attack of rheumatic fever, the patient develops choreiform motor unrest (mainly in the face, pharynx, and hands), combined with irritability and other mental abnormalities. These manifestations resolve spontaneously in a few weeks or months. The usual treatment is with highdose penicillin for at least 10 days.

Rare types of chorea include chorea gravidarum (in pregnant women), benign familial chorea, and postapoplectic hemichorea.

Treatment. Choreiform movements can be alleviated by perphenazine, tetrabenazine, tiapride, and other neuroleptic medications.

Athetosis

The neuropathological basis of athetosis is loss of neurons in the striatum, the globus pallidus, and, less commonly, the thalamus.

blubber blubber

Clinical manifestations. Athetosis generally consists of slow, irregular movements mainly affecting the distal ends of the limbs, causing extreme flexion and extension at the joints and correspondingly bizarre postures, particularly of the hands (Fig. 6.35). The interphalangeal joints may be hyperextended to the point of subluxation (“bayonet finger”). Athetosis is often found in combination with chorea (“choreoathetosis”).

Individual forms. Congenital and perinatally acquired lesions of the basal ganglia (status marmoratus, status dysmyelinisatus, severe neonatal jaundice = kernicterus) cause bilateral athetosis (athétose double), sometimes in conjunction with other signs of brain damage. Choreoathetosis and dystonia are prominent manifestations of iron deposition in the basal ganglia in pantetheine kinase-associated neurodegeneration. Focal lesions, too, e. g., an infarct, can produce hemiathetosis.

Fig. 6.35 Hand posture in athetosis.

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6

Diseases of the Brain and Meninges

134 6 Diseases of the Brain and Meninges

	Ballism	Focal Dystonia
	The neuropathological substrate of ballism is a lesion	Focal dystonia is much more common than generalized
	of the contralateral subthalamic nucleus (corpus Luysii)	dystonia. The abnormal movements are restricted to in-
	and/or its fiber connections to the thalamus.	dividual parts of the body or muscle groups. The main
	Etiology. Ballism is usually due to a focal ischemic	types of focal dystonia are the following:
		Spasmodic torticollis. In this disorder, slow contrac-
	process, less commonly to a space-occupying lesion. It
	may also be the result of severe neonatal jaundice or of a	tion of individual muscles of the neck and shoulder
	hereditary degenerative disease; it is bilateral in such	girdle produce tonic rotation of the head to a certain
	patients.	position. It is usually the contralateral sternocleidomas-
	Clinical manifestations. Rapid, lightning-like, large-	toid muscle that is most prominently affected. Only
		one-third of all patients with “wry neck” due to spas-
	amplitude, unbraked flinging movements of the limbs	modic torticollis undergo a spontaneous remission; a
	are seen on one side of the body (hemiballism) or both.	further third later develop other dystonic manifesta-
	Unlike chorea, these movements occur mainly at the	tions. The etiology usually cannot be determined and is
	proximal joints. The limbs may be hurled into stationary	presumably multifactorial.
	objects (walls, etc.), causing injury.	Blepharospasm consists of bilateral tonic contraction
	Treatment. Haloperidol and chlorpromazine can alle-
		of the orbicularis oculi muscle, often with very pro-
	viate ballistic movements. Stereotactic neurosurgical	longed, involuntary eye closure, during which the patient
	procedures are rarely indicated.	cannot voluntarily open his or her eyes. It tends to affect
		older patients, mainly women. Eye closure may be
	Dystonic Syndromes	forceful, with visible contraction of the orbicularis oculi
		muscle, or weak, with a relatively normal external ap-
	Pathology. There are no characteristic neuropathologi-
		pearance. Cases of the latter type are alternatively des-
	cal abnormalities in dystonia. To date, only a few of its	ignated lid-opening apraxia. Misdiagnosis as a psycho-
	etiologic forms have a known pathophysiological basis	genic disturbance is, unfortunately, common.
	(e. g., L-DOPA-sensitive dystonia).	Dystonia affecting multiple muscles of the head is a
	Clinical manifestations. Dystonia consists of slow,
		subcategory of focal dystonia. The various types of dys-
	long-lasting contractions of individual muscles or muscle	tonia coming under this heading are not rare when
	groups. The trunk, head, and limbs assume uncom-	taken together; they include facio-buccolingual dystonia,
	fortable or even painful positions and maintain them for	oromandibular dystonia, and Breughel or Meige syn-
	long periods of time. The various clinical types of dys-	drome. There may also be a relatively isolated dystonia of
	tonia are classified as either focal, i. e., affecting in-	the mouth, pharynx, and tongue, particularly in patients
	dividual (small) muscle groups, or generalized.	who have been treated with neuroleptics. An acute form
		can appear as a complication of antiemetic agents such
	Types of Generalized Dystonia	as metoclopramide.
	Torsion dystonias are characterized by slow, forceful,	Isolated dystonia has been described for practically
	mainly rotatory movements of the trunk and head, usu-	every muscle group in the body. Dystonia of this type
	ally accompanied by athetotic finger movements.	may be idiopathic or may arise in connection with non-
	Muscle tone is diminished at the onset of the disease. In	physiological (occupational) overuse of the muscle group
	some cases, hyperkinesia gradually ceases and gives	in question. Well-known examples include writer’s
	way to hypertonia with a rigidly maintained dystonic	cramp, hand dystonia in musicians, and foot dystonia in
	posture (myostatic form). The various types of primary	certain other occupations. Spastic dysphonia is a focal
	torsion dystonia are mostly of autosomal dominant in-	dystonia of the laryngeal musculature.
	heritance, with low penetrance, and have been localized	Etiology. Precipitating factors for dystonia can be iden-
	to genes on various chromosomes. The early-onset form
	is particularly common among Jews of Ashkenazi (East-	tified in some patients (symptomatic types of dystonia),
	ern European) ancestry and is due to a genetic defect at	but the etiology of dystonia usually remains undeter-
	the 9p34 locus.	mined.
	L-DOPA-sensitive dystonia (Segawa disease) is an au-	Treatment. Generalized dystonia can be treated with
	tosomal recessive disorder due to a genetic defect on	baclofen, carbamazepine, or trihexyphenidyl, as mono-
	chromosome 14q. It usually presents in young girls as a	therapy or in combination, but the effect of treatment is
	disturbance of gait with dystonic postures or move-	usually disappointing. A trial of L-DOPA can be reward-
	ments of the legs that vary greatly in severity over the	ing in some patients (see above). Focal dystonia can be
	course of the day. It is liable to misdiagnosis as a psycho-	successfully treated with injections of botulinus toxin A.
	genic disorder. It characteristically responds to low	Stereotactic neurosurgical procedures for dystonia are
	doses of L-DOPA (250 mg, or a little more, daily). A ther-	currently under investigation and seem to hold some
	apeutic test of L-DOPA is worth trying in any young	degree of promise.
	patient with dystonia, including sporadic forms.

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