Second edition

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364 Neurodegenerative and movement disorders
cortex (Durr et al. 1996; Ikeuchi et al. 1997; Ishikawa et al.
1999; Jobsis et al. 1997; Takiyama et al. 1994).
Differential diagnosis
Two autosomal dominant disorders to consider include dentatorubropallidoluysian
atrophy and Gerstmann–Straussler–
Scheinker disease. Dentatorubropallidoluysan atrophy is
marked, in many cases, by prominent chorea, and this may
be a clue, but genetic testing is typically required to rule out
both these disorders. Friedrich’s ataxia is suggested by an
autosomal recessive mode of inheritance and a typically early
age of onset. Multiple system atrophy of the olivopontocerebellar
type is suggested by concurrent autonomic signs and
by its sporadic nature. Other sporadic disorders to consider
include vitamin B12 deficiency, hypothyroidism, paraneoplastic
cerebellar degeneration, and alcoholic cerebellar
degeneration.
Treatment
In one double-blind study (Botez et al. 1996), amantadine
reduced ataxia in patients with SCA1 and SCA2. The
general treatment of dementia is discussed in Section 5.1,
of personality change in Section 7.2, and of psychosis in
Section 7.1.
Genetic testing should be offered to at-risk relatives.
8.18 PANTOTHENATE KINASE-ASSOCIATED
NEURODEGENERATION
Pantothenate kinase-associated neurodegeneration is a rare
autosomal recessively inherited disease due to mutations in
the gene for panthothenate kinase. It typically presents in
childhood or adolescence with a movement disorder, generally
dystonia, followed, in most, by a dementia.
The original name for this disease was Hallervorden–Spatz
disease; however, the use of this eponym is
now discouraged on ethical grounds (Shevell 2003).
Although there is no dispute that Drs Hallervorden and
Spatz originally described this disease, concerns have been
raised about honoring them with an eponym, given their
participation in the extraordinarily unethical euthanasia
programs practiced in Germany during the Third Reich.
Clinical features
The onset is typically gradual and, although most patients
fall ill in childhood or adolescence, adult-onset cases may
occur. The clinical symptomatology is heavily influenced
by the age of onset.
Childhood-onset cases (Dooling et al. 1974, 1980;
Hayflick et al. 2003; Pellecchia et al. 2005; Swaiman 1991)
are generally characterized by a slowly progressive dystonic
rigidity, prominent in both the extremities and the face;
although this dystonia may be unilateral initially, bilateral
involvement eventually occurs. Over time, other abnormal
movements may appear, including tremor or choreoathetosis;
tics have also been noted in a small minority, as
have obsessions and compulsions. Over time, a dementia
gradually appears.
Adult-onset cases (Alberca et al. 1987; Jankovic et al.
1985; Rozdilsky et al. 1968) may present with parkinsonism,
dystonia, or athetosis. Over time, and with progression
of the abnormal movements, a dementia may occur. Rarely
the presentation may be with dementia, followed years
later by a movement disorder (Cooper et al. 2000; Dooling
et al. 1974; Murphy et al. 1989; Rozdilsky et al. 1968). In
some cases depressive symptomatology may occur or,
rarely, delusions and hallucinations.
In addition to the abnormal movements, many patients
may also develop signs of spasticity, with hyper-reflexia
and the Babinski sign; in a minority pigmentary retinopathy
may occur.
Magnetic resonance scanning generally reveals the distinctive
‘eye of the tiger’ sign (Angelini et al. 1992). On T2weighted
scans, increased signal intensity is seen in the
lateral aspect of the globus pallidus, whereas on the inner
aspect there is a gross loss of signal intensity: the overall
effect, seen on axial imaging, is of looking a tiger in the eye.
Course
Childhood-onset cases show gradual progression, with
death occurring within 10–15 years; adult-onset cases tend
to pursue a much more leisurely course, and some patients
may remain ambulatory for decades.
Etiology
As noted earlier, this is a recessively inherited disorder, and
mutations are found in the gene for pantothenate
kinase, PANK2, found on chromosome 20 (Zhou et al.
2001). Macroscopically, the globus pallidus is atrophic and
exhibits a rust-brown discoloration. Microscopically, iron
deposition and axonal spheroids are seen not only in the
globus pallidus but also in the pars reticulata of the substantia
nigra and in the cerebral cortex (Dooling et al.
1974).
Differential diagnosis
In childhood- or adolescent-onset cases, consideration
must be given to Wilson’s disease, idiopathic torsion dystonia,
and dopa-responsive dystonia. In adult-onset cases,
given the variety of abnormal movements seen, the differential
is very wide and the reader is directed to Sections 3.5,