Secondary Schizophrenia (143 page)

dromes. Clinical features are described in the subsec-nitive and behavioral abnormalities
[44, 54].
The
tions that follow.

dementia found in individuals with FD differs clin-

ically, neuropsychologically, and pathologically from
Psychiatric features

Alzheimer’s Disease
[21,
50],
and, although typically
Psychosis and/or mood disorders may occur in combi-progressive, it is of the fronto-subcortical type
[4,

nation with neurological symptoms
[9].
Alternatively,
7, 9,
45].
The neuropathology of dementia associ-subcortical lesions may appear with psychiatric symp-ated with FD involves fronto-temporal atrophy, neo-

toms without the concurrent involvement of motor cir-cortical neurofibrillary tangles, and neuronal loss in
cuits that produce clinically significant motor symp-the nucleus basalis of Meynert but senile plaques are
toms
[44].
Psychotic symptoms include auditory and
absent
[55].
Other features include calcareous deposi-visual hallucinations, paranoid delusions or paranoid
tion, white-matter demyelination, and fibrous gliosis
trends, ideas of reference, ideas of influence, catato-

[14].
Dementia has also been associated with centrum
nia, fugue states, and atypical features such as com-semiovale calcification
[56].

plex perceptual distortions
[45, 46, 47, 48].
Although
Cognitive abnormalities include slow mentation,

a link between psychotic symptoms and basal ganglia

poor concentration and attention, as well as mild

pathology is supported, symptoms appear to be vari-

to moderate impairment of verbal and nonverbal

able after the onset of neuronal damage and remis-

memory with normal language, abstraction, construc-

sion has also been reported
[4]
. IBGC is also associ-tion, and praxis
[57, 58].
Palilalia and dysarthria
ated with a schizophrenia-like-psychosis
[4, 7,
45, 49].

may be prominent
[59].
Anterograde amnesia, atten-Chabot and colleagues
[4]
found that the risk of psy-tional impairment, and severe disexecutive syndrome,
chosis was proportional to the extent of calcification
including impairment in planning, problem solving,

although Brodaty and colleagues
[50]
reported no sig-set shifting, flexibility, and divergent thinking, have
nificant association between the extent of BGC and

also been reported
[44].
Brodaty and colleagues
[50]

psychiatric status.

found no significant relationship between IBGC sta-

Although the psychiatric manifestations of FD are

tus and cognitive impairment or dementia. Konig

varied, the most prominent are mood disorders occur-

[14]
reported no direct associations in etiology, local-

360

ring in 20%–30% of patients. These can include depres-ization, volume, or symptoms except that extensive
Chapter 29 – Fahr’s Disease and psychosis

BG sclerosis is associated with more severe mental

Addison’s Disease
[74]
, and an inborn error of
deterioration.

vitamin D metabolism (i.e., reduced 25-OH

vitamin D3 with normal levels of 1–25(OH)2

Differential diagnosis

vitaminD3)
[79].

4. Genetic/congenital conditions, including birth

FD should be distinguished from incidentally found

anoxia
[51,
80]
, oculocraniosomatic disease
[81],

BGC with or without associated clinical neuropsychi-

and Down’s Syndrome
[66, 82].
Microencephaly,
atric features
[11].
Principal causes of bilateral BGC

pigmentary macular degeneration, progeria, and

include hypoparathyroidism, pseudohypoparathy-

abnormal calcium metabolism can also be

roidism, and Albright’s hereditary osteodystrophy

associated with infantile and juvenile BGC
[11].

[4].
Developmental defects should also be ruled out
5. Infectious and inflammatory conditions

[27]
. Brain CT scan is considered standard clinical
associated with BGC, including neurobrucellosis

practice and is sensitive in demonstrating minimal

[83],
congenital rubella
[73],
toxoplasmosis
[73,

BGC calcification
[60].
CT appears to be superior to
80],
chorea
[74],
cerebral malaria
[74],
and
MRI for evaluating the presence of mineral deposits
encephalitis
[74, 80].
BGC can also occur in
in brain tissue. Radiological findings vary from

patients with abnormal calcium metabolism in

barely detectable dust-like opacification to significant
AIDS
[84, 85].

radiodensities
[32].
Recognition of calcifications on
CT scan is straightforward due to the high resolving
Natural history and prognosis

capability of CT and because calcifications consist

of hydroxyapatite similar to that of bones
[27,
61].

Three forms of the disease have been described: a

Although MRI correlates better with functional

childhood form with onset in infancy and death within
impairment
[27,
56],
calcification signals may remain
the first few years of life
[86, 87];
an early-adult-onset
undetected on MRI scans when they are at an

type with presentation between 20 and 40 years of age
intermediary stage
[62].
Hyperintense T2-weighted
and manifesting initially as a psychosis; and a late-images may reflect a slowly progressive metabolic or
onset variety typically presenting between the ages of
inflammatory process that subsequently calcifies and
40 and 60
[7,
88].

is probably responsible for neurological deficits
[56].

The course of FD is characteristically slow and pro-

gressive. Neurological or psychiatric symptoms such as
Causes of basal ganglia calcification

psychosis tend to precede cognitive decline. BGC may
be detected before clinical symptoms develop. Indi-

Basal ganglia calcification can occur in numerous dif-viduals presenting with psychosis, for example, may
ferent disorders (see Table 5, p. 75 in
[37]
for a com-develop dementia and motor disturbances later in life
prehensive list). A summary of these falls into the fol-

[58].

lowing categories:

1. Neurological conditions, including CNS lupus

Treatment

[63, 64]
, tuberous sclerosis
[65],
early-onset
Selective removal of deposited calcium from brain tis-Alzheimer’s Disease
[66],
atypical senile dementia
sue is not possible; although calcium is the major min-

[67],
motor neuron disease
[68],
myotonic
eral deposited, other minerals are also implicated
[3].

muscular distrophy
[69]
and mitochondrial
Treatments with CNS-specific calcium channel block-

encephalopathies
[70, 71].

ing agents have been unsuccessful [Manyam unpub-

2. Chemically induced or iatrogenic conditions,

lished in
3].
Likewise, no specific treatments to limit
including therapeutic radiation
[15,
65, 72],

calcification progression are available apart from a
carbon monoxide poisoning
[73, 74],
lead
theoretically appealing, yet unconfirmed report of

intoxication
[73],
methotrexate treatment
[15],

improvement using chelators (xydifon, penicillamine,
and long-term anticonvulsant therapy
[13,
75].

deferoxamine), antioxidants, and calcium antago-

3. Metabolic conditions, including hypercalcemia

nists
[89].
Loeb
[90]
reports sustained symptomatic
[12, 29],
hypoparathyroidism
[76],

improvement in a case of familial idiopathic cere-

pseudohypoparathyroidism
[32, 59,
77],

bral calcification with disodium etidronate, a bisphos-

361

pseudo-pseudohypoparathyroidism
[32, 59,
78],

phonate, without reduction in calcification. Although
Organic Syndromes of Schizophrenia – Section 3

specific treatment for FD is unavailable, in the case of
[1].
Pharmacologic therapies typically used for move-FS the primary causes should be treated
[9].

ment disorders may alleviate dystonia and other invol-Limited literature and few data on the appropri-

untary movements. Appropriate antiepileptic medica-

ate treatment of psychiatric symptoms in FD are avail-tions should be prescribed for seizure control
[93].

able to guide clinicians
[11].
Patients may be particularly susceptible to neuroleptic malignant syndrome
Implications for clinical practice

[88, 91]
and extrapyramidal side effects with antipsychotic medication
[92].
As yet, there are no system-Fahr’s Disease is an uncommon condition. Clinicians
atically conducted controlled psychotropic treatment
should consider the diagnosis in patients who present
studies in FD
[11].

with (i) the characteristic triad of neurological, cognitive, and psychiatric symptoms; (ii) some of these
Management

symptoms and BGC on CT scan; or (iii) some of these

symptoms, extrapyramidal signs, and poor response to
Aspects of management can be categorized accord-

antiparkinsonian treatment. A detailed family history
ing to symptoms. Testing and counseling for genetic

can assist with diagnosis and may have implications for
susceptibility may be warranted; prenatal testing is
genetic counseling.

unavailable and linkage testing is available on a

research basis only
[93].

For psychiatric symptoms, antipsychotics, antide-

Suggestions for future research

pressants, general support, and psychotherapy, as

Although FD is uncommon, it may provide a heuristic

indicated, may be helpful. Psychosis responds unpre-

window. Further investigation of FD may contribute to
dictably to treatment and is, on occasion, unrespon-

the understanding of psychosis through the study of

sive
[7,
88, 94].
Neuroleptic medication should be
correlations between localized lesions, clinical symp-used with caution as it may potentiate extrapyramidal
toms, and cerebral imaging abnormalities in a homo-

symptoms
[7].
Some success has been achieved with
geneous group. Such study is likely to further knowl-lithium in individuals whose symptoms have proven
edge of the pathophysiology of the psychotic symp-

refractory to haloperidol
[95].
Patients with IBGC and
toms
[4].

depression have been shown to respond to antide-

Research may focus on correlations between neu-

pressant treatments, including imipramine and ECT

ropsychiatric symptoms and genes, neuropathology

[11].
However, given the variable presence of increased
and neuroimaging. Little is known about the longitu-

intracranial pressure and the risk of seizures in this
dinal course of the disease, and long-term follow-up
group, ECT may be ill advised
[11].
Appropriate phar-could elucidate the relationship between radiological
macological treatment may improve symptoms of anx-

changes and neuropsychiatric manifestations. Corre-

iety and obsessive-compulsive disorder
[93].

lation of neuropsychiatric findings with disease stage,
Management of cognitive symptoms follows the

clinical signs, and radiologic, metabolic, physiologic,
general lines of dementia care, including support for
and pathologic markers of disease may add to the

families and referral to Alzheimer’s associations. No
understanding of this condition
[11].