Secondary Schizophrenia (97 page)

the peroxisome
[67, 68].
It classically afflicts young
[74].

Organic Syndromes of Schizophrenia – Section 3

Prevalence

of a brain tumor
[115, 116, 117, 118].
In three cases,
the disease process appears to have been triggered by
The incidence of ALD is unknown but an estimate of at
a head injury, with pathological changes beginning in
least 1:17,000 has been cited
[67, 76].
This figure would
the same location as the trauma
[99,
119].

be most accurate for the severe infantile form, which is
a rapidly progressive, fatal, neurodegenerative disease
[77, 78, 79, 80]
but is likely to be an underestimation
Investigations

for the milder, late-onset variants of adolescence and
Young men with a schizophrenic syndrome should be
adulthood.

screened for ALD if they have a history of Addison’s
Disease, an earlier diagnosis of attention deficit dis-Psychiatric features
order, a disorganized type of psychosis, cranial MRI
There is very little information on the incidence or
showing symmetric white-matter pathology, cognitive
prevalence of psychiatric symptomatology in patients
decline, seizures, or a family history of multiple sclero-with “adult-onset” ALD, and most published reports
sis in female relatives.

provide few details regarding patients’ mental status.

The definitive diagnostic test is measurement of
Of the 41
[81, 82,
83, 84, 85, 86, 87, 88, 89, 90, 91, 92,

VLCFA in serum, preferably when the patient is in
93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,

a fasting state. Most laboratories measure the abso-

106, 107, 108, 109, 110, 111, 112,
113, 114]
late-onset
lute concentration of C26:0, hexacosanoic acid, and
cases we identified in the English literature up to 2006,
the ratio of C26:0/C22:0 and C24:0/C22:0
[68].
Lev-24 (58%) were reported to have psychiatric features,
els are identical across different forms of the disease
and in 17
(Table 18.1)
a detailed psychiatric assessment
[120].
In patients who test positive, baseline levels of
was provided. Behavioral disturbance or personality
ACTH and cortisol should be determined. In addi-change was often the earliest reported finding. Features
tion, an ACTH stimulation test should be performed
of mania were present in 9 (53%) of the 17 patients
to evaluate adrenal reserve. Adrenal insufficiency can
and 5 (30%) were psychotic. Many patients were
be life-threatening and regular reassessment of adrenal
treatment-resistant and appeared to have an aggressive
function should be done.

course of illness. Eventual cognitive impairment was
common.

Treatment

Although there is no definitive treatment for ALD, the
Neurological features and endocrine

following are being actively studied:

abnormalities

1. Lorenzo’s oil (LO), a 4:1 mixture of glyceryl
Gait impairment was the most common initial neu-trioleate and glyceryl triurecate, when combined
rological complaint in 91% of adult-onset cases fol-with reduction of other fats, has been shown to
lowed by peripheral neuropathy (58%), visual impair-lower serum levels of VLCFA. Although the effect
ment (21%), seizures (20%), and dysarthria (20%).

on course of illness has been disappointing, a
Most patients developed upper motor neuron pathol-recent study demonstrated that genetically
ogy, affecting the legs in particular. Twenty-five (60%)
affected boys with normal cranial MRIs had

of the 41 cases had biochemical evidence of adrenal
a reduced risk of developing the cerebral

insufficiency. The average age at the time of diagnosis
form of the disorder when treated with LO

of Addison’s Disease was 29
±
6 years.

[121, 122].

2. Hematopoetic stem cell transplantation has been
Neuroimaging

considered for adults with early cerebral

MRI scanning typically shows T2-weighted symmet-involvement
[76]
. This intervention is,
rical hyperintensities involving the parieto-occipital
unfortunately, associated with considerable

regions. As the disease progresses, demyelination
risk and is, therefore, not recommended for

moves forward to involve the frontal lobes. Atypi-individuals without MRI evidence of
cal findings include early frontal lobe involvement
inflammatory disease, given that only 50% of
(in approximately 15% of patients), early cerebellar
those with ALD will go on to develop this

244

involvement, or an asymmetric mass lesion suggestive
problem.

Table 18.1
Neuropsychiatric and adrenal findings in 17 cases of late-onset adrenoleukodystrophy
Age of

Psychiatric

Neurologic

Adrenal

onset

Reference

findings

findings

involvement

Neuroimaging

Course of illness

26

Gray [

At age 23: change in

Staggering and

Hyperpigmentation

None

1 year later, patient

xlink:href="c-

behavior,

dragging left

but normal ACTH

incontinent of urine,

12345-

irresponsible,

leg for 3 weeks;

level and normal

increasingly more

bib81">81]

stealing. At age 26:

hyperreflexia,

stimulation test

facile, emotionally

disinhibition,

bilateral

labile, and

emotional lability,

extensor

disinhibited; no

distractible,

plantars

progression of other

hyperkinetic

neurologic symptoms

16

James
et al.

Withdrawn,

Left extensor

Hyperpigmentation; CT: dilation of

By age 17, florid

[

inattentive, anxious,

plantar, severe

ACTH level

posterior walls of

psychosis with

xlink:href="c-

violent

memory

markedly elevated

lateral ventricle

auditory

12345-

dysfunction

hallucinations,

bib91">91]

delusions of passivity,

paranoia. At age 20

developed seizures.

Decline in IQ from 75

at age 15 to 59 by

age 28

21

Sereni
et al.

Withdrawn,

Left extensor

Hyperpigmentation; MRI: bilateral

6 months after

[

inattentive, anxious,

plantar, severe

ACTH level

demyelination

admission, developed

xlink:href="c-

violent

memory

markedly elevated

involving temporal,

ataxia, bilateral

12345-

dysfunction

parietal and occipital

extensor plantars; left

bib92">92]

regions, right > left

homonymous

hemianopia;

constructive apraxia;

death 8 months after

presentation

31

Menza
et al.

Began at age 26:

Urinary and

Adrenal

CT: some ventricular

Developed cognitive

[

substance abuse;

fecal

insufficiency (on

enlargement

impairment 6 months

xlink:href="c-

agitated, irritable,

incontinence;

replacement

later

12345-

intrusive, hyperactive,

bilateral

therapy)

bib95">95]

sexually

extensor

inappropriate, loud

plantars

pressured speech,

euphoric. Diagnosis:

bipolar affective

disorder

33

Menza
et al.

Numerous

None at

None

CT: ventricular

Memory impairment

[

hospitalizations,

presentation

enlargement with

2 years later;

xlink:href="c-

alcohol abuse;

periventricular WM

incontinent, ataxic,

12345-

depression, multiple

lucencies

bilateral extensor

bib95">95]

suicide attempts,

plantars; progressive

auditory

dementia

hallucinations, poor

impulse control,

irritability, paranoid

delusions, pressured

speech. Diagnosis:

schizophrenia

48

Panegyres

Personality changes,

Incontinence,

None

CT: widespread WMD

At age 53, developed

et al.
[

depression,

bilateral

with contrast

seizures and

xlink:href="c-

increasingly

extensor

enhancement of

dementia and died

12345-

uncommunicative,

plantars

corpus callosum,

soon after from

bib98">98]

abusive, sexually

occipital and

pulmonary embolism

aggressive, several

temporal lobes

suicide attempts

57

Weller
et al.

Disoriented,

Slow apraxic

None

MRI: diffuse left

One year later, severe

[

hypomanic, marked

gait, fluent

hemispheric

dementia, global

xlink:href="c-

disinhibition

asphasia, alexia,

demyelination

apraxia, right

12345-

dysgraphia,

involving left

hemiparesis, and

bib99">99]

dyscalculia,

frontotemporal and

urinary incontinence

right

occipital regions,

(cont.)

Table 18.1
(cont.)

Age of

Psychiatric

Neurologic

Adrenal

onset

Reference

findings

findings

involvement

Neuroimaging

Course of illness

homonymous

corpus callosum and

hemianopia,

cerebral peduncle

right extensor

plantar

response

28

Angus
et al.

Disturbed personality; Mild spastic

None

MRI: increased

Unknown

[

disinhibited, loud;

paraparesis

periventricular

xlink:href="c-

self-neglect

T2-weighted signal

12345-

bib100">100]

24

Angus
et al.

At age 24: diagnosed

None

None initially;

MRI: multiple

At age 34, developed

[

with schizophrenia

elevated ACTH at

T2-weighted

orofacial dyskinesia,

xlink:href="c-

with delusional

age 34

hyperintensities in

choreoathetosis; by

12345-

thoughts,

trigone and splenium

age 37, emaciated,

bib100">100]