Secondary Schizophrenia (142 page)

1997.
41
:433–40.

survival and decreased abnormal

67. Vincent J. B., Paterson A. D.,

movements in transgenic model

64. Leroi I., O’Hearn E., Margolis R.

Strong E.,
et al.
The unstable

of Huntington’s Disease, with

L. Psychiatric syndromes in

trinucleotide repeat story of major

administration of the

cerebellar degeneration. Int Rev

psychosis. Am J Med Genet, 2000.

transglutaminase inhibitor

Psychiatry, 2001.
13
:323–9.

97
:77–97.

357

Section 3

Organic syndromes of schizophrenia: genetic disorders related to SLP

29 Fahr’sDiseaseandpsychosis

Kim Burns and Henry Brodaty

Facts box

abnormalities, generally hereditary with an autoso-r
mal dominant transmission
[4].
IBGC is characterized
Fahr’s Syndrome and Fahr’s Disease are

by radiological, neurological, cognitive, and psychi-characterized by radiological, neurological,
atric abnormalities. However, a form of the disorder in
cognitive, and psychiatric abnormalities,
which calcification is inherited independently of neu-although variable presentations are
rological, cognitive, and psychiatric symptoms has also
described.

been identified
[5].

r
Symmetrical, bilateral basal ganglia

Fahr’s Disease is variably differentiated from Fahr’s
calcification (BGC) occurs without physical
Syndrome (FS), in which BGC occurs secondary to
abnormalities.

another disorder. The distinction may be immaterial,
r
The underlying etiology and pathogeneses
however, as psychiatric symptoms in both FD and syn-remain unclear.

drome are possibly mediated by basal ganglia (BG)
r
BGC occurs in many other conditions,

dysfunction rather than the effects of the primary
suggesting a common pathogenic pathway.

disorder. Intracranial calcification on CT scanning is
r

indistinguishable between the two conditions
[6, 7, 8]

Psychotic symptoms include auditory and

and FS and FD are also differentiated from “radiologi-visual hallucinations, paranoid delusions or
cal” BGC without clinical features
[9].

paranoid trends, ideas of reference, ideas of
influence, catatonia, fugue states, and

atypical features, such as complex perceptual
Prevalence and incidence

distortions.

r
Although a link between psychotic

Fahr’s Disease is a rare disorder
[3],
and an incidental
symptoms and basal ganglia pathology is

finding of BGC does not equal FS
[10].
BGC is a com-supported, symptoms appear to be variable
mon finding on routine CT brain scans, estimated to
after the onset of neuronal damage and

occur in 0.93% of cases presenting for neuroimaging.

remission has been reported.

Before the availability of CT scans, diagnosis was made
r

based on skull roentgenogram or autopsy. The num-Treatment is largely symptomatic.

r

ber of cases of intracranial calcifications diagnosed has
Patients may be particularly susceptible to
increased with the advent of head CT scans
[1].

neuroleptic malignant syndrome and

Lauterbach
[11]
reviewed seven studies and found
extrapyramidal side effects with

BGC in 274 of 29,484 cases
[10, 12, 13, 14, 15, 16].

antipsychotic medication.

Kobari
[17]
reviewed three studies and found brain
calcification in approximately 0.3 to 1.2%
[12, 18,

Fahr’s Disease (FD) or idiopathic basal ganglia
19]
. Reported rates of neurological abnormalities in
calcification (IBGC) is also known as bilateral stri-patients with CT evidence of BGC vary between 0%

atopallidodentate calcinosis
[1],
morbus Fahr, stri-

[10]
and 20%
[13]
. Logically, the prevalence of FS in
atopallidodentate calcification, and calcinosis nucleo-the general population should be less than the 0.5%

rum cerebri
[2].
Manyam
[3]
quotes 35 different names
prevalence reported in patients receiving CT scans
[2].

for this syndrome. It is described as symmetrical, bilat-Although the true prevalence of FD is unknown, it is
eral BGC without parathyroid dysfunction or physical
highly probable that it must be rarer still.

358

Chapter 29 – Fahr’s Disease and psychosis

Basal ganglia

Lowenthal
[32]
set down criteria for the definition
of FS (including FD), but these have not gained cur-The basal ganglia are large subcortical nuclear masses
rency. The calcification must (i) have a characteristic
grouped on the basis of their interconnections.

distribution, involving at least the globus pallidus, with
Although there is some debate as to which struc-or without cerebellar calcification; (ii) be evident on
tures should be included within the basal ganglia, it
CT, and (iii) be of sufficient size to be detected on a
is generally agreed that the core components include

macroscopic pathological exam.

the caudate nucleus, nucleus accumbens, putamen,

Although calcifications tend to occur in the den-

and globus pallidus. The caudate nucleus and puta-

tate nuclei and basal ganglia, as well as the cerebellar
men together are called the striatum; the putamen and
and cerebral white matter
[27],
the most common dis-globus pallidus are together described as the lentiform
tribution of calcification in FD is limited to the globus
nucleus
[9, 20].

pallidus
[25].

The basal ganglia play an important role in the

Chabot
[4]
subdivided FD according to the severity
regulation of mood, emotion, motivation, and cogni-

of the pathology: massive, affecting the pallidum, stria-tion as well as motor control
[20, 21].
They have a
tum, dentate nuclei; medium, affecting the pallidum

high metabolic rate, a peculiar vascular supply, and
and striatum; and mild, affecting the pallidum only.

autoregulation facilitating increased vascular perme-Microscopically, calcifications generally develop
ability
[22, 23].
Functions include motor learning,
within vessel walls and the perivascular space, ulti-sequencing and movements, attentional allocation and
mately extending toward neurons, which can remain

filtering, working memory, implicit learning, memory
undamaged for some time
[4].
Progressive basal gan-

[9]
and possibly reward processes
[24].

glia mineralization can compress the vessel lumen,

Psychiatric symptoms, frequently seen in dis-

thus initiating a cycle of impaired blood flow, neural
eases of the basal ganglia such as Fahr’s, Parkinson’s,
tissue injury, and mineral deposition
[22, 23].
The cal-Wilson’s, and Huntington’s Diseases, are thought to be
cifications of the finer cerebral vessels are concentrated
due to disruption of cortical-subcortical circuits medi-in the walls of arterioles and capillaries as well as in the
ated by the basal ganglia
[25].
BGC may reflect or cause
perivascular parenchyma of the grey and white matter
dysfunction of the basal ganglia-thalamo-cortical cir-

[Bamberger 1855 in
27,
33, 34, 35].

cuit that leads to these symptoms
[26].

Calcifications are composed of not only calcium

but also iron, zinc, and aluminum
[36].
Additionally,
Etiology

basal ganglia concretions contain copper, magnesium,
and potassium within an organic matrix [Hurst 1926

Although FD has generally been considered to be idio-in
33, 37, 38, 39].
The mineral composition varies by
pathic, genetics appears to play a part. An autosomal
anatomic site and proximity to vasculature
[40].
Defec-dominant pattern of inheritance has been described in
tive iron transport and free radical production may

10 out of 11 families with familial IBGC
[17, 27, 28,

damage tissue, initiating calcification
[41].
Calcium
29]
and possibly an autosomal recessive pattern in one
deposits appear to be deposited secondarily around a
family
[3, 30].
A linkage to chromosome 14q in a fam-nidus composed of mucopolysaccharides and related
ily with multiple affected members has been described,
substances
[33, 34, 35].
When mineral deposits are
in which genetic anticipation was also found
[31].
The
extensive, “brain stones” develop
[37].

associations between these abnormal phenotypes and

At the microscopic level, basal ganglia (BG) con-

abnormal genes remain unclear despite the mapping to
cretions are recognized as basophilic globules track-chromosome 14q of a susceptibility locus for FD
[5].

ing the vessel walls of arteries, arterioles, capillaries,
and veins. Scanning electron microscopy has shown a

connection between some of the spherical and hemi-

Pathogenesis and pathology

spherical bodies that were formed in the adventitial
The key feature of FD is mineralization, especially cal-cells of blood vessels and surrounding glial cells
[42].

cification. Although other minerals are present, the
The intima of involved vessels is usually preserved but
calcium is radiopaque and present in the greatest

occasionally proliferates to narrow the lumen
[37].

quantities
[3].
The cause of this is not known, although
The pathophysiological mechanisms leading to cal-

359

genetics play a part.

cification formation are unclear
[32, 36].
Fahr-type
Organic Syndromes of Schizophrenia – Section 3

calcification has been reported in several neurodegension, mania, or bipolar disorder. Anxiety disorders are
erative disorders, such as diffuse neurofibrillary tan-common, with up to 30% of patients presenting with
gles with calcification and Alzheimer’s Disease
[43].

obsessive-compulsive disorders
[14,
51].

Clinical features

Neurological features

There is great variability in the presentation of FD.

A variety of neurological manifestations have been

Although the condition presents most commonly with

described. Movement disorders such as parkinson-

motor deficits, approximately 40% of those with the

ism, paresis, dystonia, and speech impairment are

disease present with primarily cognitive and other psy-often present
[9].
Extrapyramidal symptoms com-chiatric symptoms
[11].
Clinical features are reported
monly include chorea and ataxia, although individ-

as individual or family case studies because the con-uals may present with mixed extrapyramidal symp-

dition is rare. Inconsistency and latency of clinical
toms
[37].
Pyramidal signs can also occur
[27]
. Other
features are thought to occur because calcification is
neurological features can include stroke-like events,
often present for an extended period before neuronal
tremor, myoclonus, spasticity, epileptic seizures, and
impairment is evident
[4].
In a study of 38 cases with
coma
[9]
. The location of the calcification does not
FD, Manyam
[1]
found a significantly greater degree
necessarily correlate with the neurological signs
[7, 19,

of calcification in symptomatic patients when com-

28,
52, 53].

pared to those who were asymptomatic. Konig
[14]

suggests that the time of occurrence of calcification
Cognitive features

may be important so that early-life depositions are

Cognitive disorders such as apathy, amnesia, and

associated with oligophrenia, later dates with various
dementia may be present
[36].
FD may present as
mood changes, and still later dates with dementia syn-neurologically asymptomatic with pronounced cog-