Diagnosis and management of early- and late-onset cerebellar ataxia

peduncles on T2-weighted images. Increased
putaminal hypointensities on T2-weighted gradient
echo imaging are more common in MSA than
in Parkinson disease, and combination with
a hyperintense slit-like band lateral to the putamen
may be specific for MSA. Pathologically,
MSA is an a-synucleinopathy, with glial cytoplasmic
inclusions (58).
Therapeutic strategies
Treatment of the underlying disorder is the first
step in symptomatic ataxia. Intoxications, vitamin
deficiencies and endocrine disorders, for
example, are treatable causes of ataxia. Treatment
of underlying malignancy may improve or
cure paraneoplastic syndromes. Although there
is an increasing insight into genetic and pathophysiological
mechanisms underlying hereditary
ataxias, therapeutic options modifying neurodegeneration
are still very limited (59). This does
not, however, diminish the importance of an
adequate diagnosis for the identification of
potentially treatable disorders. In autosomal
dominant EA, acetazolamide is very effective,
especially in EA2. Acetazolamide and also
gabapentin have shown some improvement in
cerebellar signs in SCA in open trials, but these
effects have to be confirmed in further studies
(59). In the autosomal recessive ataxia subtypes,
daily supplementation of vitamin E in AVED
prevents further neurodegeneration (26). Dietary
treatment in Refsum’s disease, the restriction of
intake of phytanic acid, may prevent onset of
symptoms (26). Treatment of CTX with chenodeoxycholic
acid stabilizes or lessens the symptoms
(39). In all patients with cerebellar ataxia,
symptomatic therapy may relieve symptoms.
Spasmolytic drugs such as baclofen may be used
to treat spasticity, and in selected patients
botulinum toxin may be considered, which is
also effective in treatment of dystonia. Dystonia,
tremor or bradykinesia may be an indication for
dopaminergic and anticholinergic therapy. Anticholinergic
drugs are also successful in treatment
of hypersalivation due to swallowing difficulties.
Intention tremor has been treated with betablockers,
benzodiazepines or even thalamic
stimulation (59). Muscle cramps can be relieved
with for instance benzodiazepines (clonazepam).
Conclusive remarks
This review illustrates the broad clinical spectrum
of disorders associated with cerebellar ataxia.
For the individual patients and their family, it is
very important to come to an appropriate
Diagnosis and management of cerebellar ataxia
diagnosis. This provides insights into prognosis,
enables adequate genetic counselling in hereditary
ataxias and may have implications for therapy or
preventive screening, as described above.
We developed a diagnostic algorithm to facilitate
the diagnostic process. We do not suggest
this algorithm to be absolute or applicable for
every patient. Obviously, specific diagnostic clues
should lead to the specific use of diagnostic tests.
The cutoff point for ages at onset in the algorithm
needs flexible interpretation. For example,
some SCA subtypes, especially SCA6, may have
an onset at age above 50 years. Of course, genetic
testing is dependent on local availability. Furthermore,
frequent updating is essential with the
ongoing identification of genes associated with
ataxia. In this context, it should be mentioned
that identifying families with undiagnosed hereditary
ataxia may be valuable for linkage studies.
It is reasonable to expect that the increasing insight
into the genetic background of ataxias will
eventually lead to considerable therapeutic options
in the future. Currently, optimal treatment of patients
with ataxia requires the multidisciplinary
expertise of neurologist, professionals in the field
of revalidation and clinical geneticist. In addition,
foundations of patients with (hereditary) ataxias
may be very useful as a source of information
and support for patients and their families.
Notes
Supplementary information for Figure 1
1. To obtain further phenotypic clues, consider
for example electromyography, ophthalmologic
or cardiologic screening or consultation of
clinical geneticist.
2. EA1 vs EA2:
EA1 EA2
KCNA1 gene CACNA1A gene
Kinesigenic EA Nonkinesiogenic EA
Brief attacks (,15 min) Variable attacks: minutes to
hours (days)
Interictal myokemia Eventually interictal
cerebellar signs
Acetazolamide may
be effective
(nystagmus, ataxia)
Acetazolamide very
effective
3. SCA with retinopathy: start with SCA7;
otherwise start with SCA1, 2, 3, 6, and 7;
second-line testing: DRPLA, SCA(8), 12, 14,
17, 27 (adjust for local situation, depending on
regional prevalences of SCA subtypes and
availability of gene analysis).
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