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S U M M A RY
Background An 83-year-old man presented with hypertension,
CME
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On the basis of the patients clinical presentation and neurological examination findings as
well as his previous neuroimaging and diagnostic studies, a genetic ataxia syndrome was
considered. Given his lack of a family history of
ataxia, genetic evaluation was directed towards a
sporadic hereditary ataxic condition. This testing
was positive for a disease-associated CAG repeat
expansion in the gene for autosomal dominant
spinocerebellar ataxia (SCA) type 6, with 11
repeats on the normal allele and an abnormal
22 repeats on the affected allele.
The patient was treated empirically with
buspirone 5 mg twice daily, which was slowly
titrated to 15 mg twice daily over 4 weeks,
resulting in a mild subjective improvement in his
balance after 3 months. He was referred to physical, occupational, and speech therapy clinics for
gait retraining, assessment for an assistive device,
home safety, and management of his dysarthria
and dysphagia. Genetic counseling was also
offered to the patient and other family members
who were considered to be at risk.
DISCUSSION OF DIAGNOSIS
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Investigation
Primary laboratory testing
Serum electrolytes
Metabolic abnormalities
Lymphoproliferative disorders
Renal function
Renal disease
Liver function
Hepatic disease
Inflammation/vasculitis
Neurosyphilis
Thyroid-stimulating hormone
Hyperthyroidism/hypothyroidism
Diabetes mellitus
Vitamin B12
Methylmalonic acid
Homocysteine
Folate
Folate deficiency
Vitamin E
Vitamin E deficiency
Stroke
Subcortical vascular disease
Neoplasm
Structural anomaly
Multiple sclerosis (MS)
Normal pressure hydrocephalus
(NPH)
Leukodystrophy
CreutzfeldtJakob disease (CJD)
Neurodegeneration
Malignancy
aSelected
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Table 2 Recommended secondary clinical evaluation for acquired causes of ataxia in an adult patient.
Tier denoting
frequency of use
in the evaluation
Differential diagnosisb
Secondary
diagnostic studiesa
Differential
diagnosisb
Ic
Sarcoidosis
Ammonia
Electroencephalogram
(EEG)
Epilepsy/
CreutzfeldtJakob
disease (CJD)
Ceruloplasmin
Copper
Copper myelopathy,
Wilsons disease
Neuropathy
Myopathy
Fasting lipids
Electromyogram
(EMG)/nerve
conduction velocity
(NCV)
Lactate
Pyruvate
Mitochondrial disease
Lymphoproliferative disorders
Somatosensory
evoked potential
(SSEP)/visual
evoked potential
(VEP)
Neurodegenerative/
demyelinating
disease
Serum ketones
Metabolic disorders
Antigliadin antibodies
Gluten-sensitive enteropathy
Anti-GAD65 antibodies
Autonomic testing/
orthostatics
Multiple system
atrophy
Anti-cerebellar antibodies
(Hu, Yo, Ri, Ma, Ta, CARP 8, CV2,
Tr, LEMS, mGluR1, CRMP5, GQ1b,
amphiphysin, PCA-2, and others)
FDG-PET scan
Metabolic disorders
Muscle biopsy
Mitochondrial
disease
HIV
Lyme titers
SSA/SSB antibodies
Sjgrens syndrome
[18F]fluoro-L-DOPA
(FDOPA)-PET scan
Parkinsons disease
Magnetic resonance
spectroscopy
Metabolic disorders
Nerve biopsy
Neuropathy
Lysosomal screen
Lymphoproliferative
disorders
Brain biopsy
Prion disease
Peroxisomal disorders
Conjunctival or skin
biopsy
Storage disorders
IId
IIId
IVe
aNote that not all patients will require all tests or studies listed, and the evaluation should be guided by clinical phenotype and neurological examination.
bSelected differential diagnoses are shown in association with each test or study. cIncludes general tests and common studies that will be required by most
patients with a normal initial screen. dIncludes autoimmune/infectious and cerebrospinal fluid tests, as well as more-specific diagnostic tests that may be
required in certain patients. eIncludes tests and studies that are only useful in specific subsets of ataxia patients. Abbreviations: anti-GAD65; anti-glutamic acid
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Genetic considerations
Friedreichs ataxia
Ataxia with oculomotor apraxia type 1 (AOA1)
Ataxia with oculomotor apraxia type 2 (AOA2)
TaySachs disease
Metabolic disordersc
Mitochondrial disordersc
Leukodystrophiesc
aSelected
hereditary syndromes to consider in an adult patient with progressive ataxia are shown. The selection of tests
to perform should be directed towards the patients phenotype, neurological features, and previous diagnostic evaluation.
Not all available genetic tests for hereditary ataxias are listed. See also Supplementary Table 1 online for a list of internet
sites that might be useful in the selection of genetic tests for individual patients. bNote that spinocerebellar ataxias can be
phenotypically heterogeneous, thus the subtypes listed are those with genetic testing available. cSpecific tests vary and are
dependant on clinical phenotype.
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Medicationa
Suggested dosageb
Selected referencec
Cerebellar ataxia
Amantadine
Buspirone
L-Tryptophan
Acetazolamide
Branched-chain amino acids
D-Cycloserine
25150 mg b.i.d.
530 mg b.i.d.
6001,000 mg q.d.
4 g/day b.i.d.q.i.d.
1.53.0 g q.d.
25 mg b.i.d.
Cerebellar tremor
Primidone
Propranolol
Clonazepam
Carbamazepine
Ondansetron
Valproate
Zonisamide
Topiramate
Levetiracetam
Up to 500 mg t.i.d.
Up to 240 mg/day
0.52.0 mg q.d.
100400 mg t.i.d.
Up to 48 mg t.i.d.
250 mg q.d.1,000 mg b.i.d.
100 mg q.d.300 mg b.i.d.
25100 mg b.i.d.
Up to 50 mg/kg/day
Central nystagmus
Clonazepam
Baclofen
Gabapentin
Aminopyridines
0.52.0 mg q.d.
Up to 40 mg t.i.d.
3001,600 mg t.i.d.
Varies by compound; up to 80 mg/day for
3,4 diaminopyridine (3,4-DAP)
520 mg/day
Memantine
aPlease note that none of these medications has FDA approval in the US for use in this capacity. bDosages are suggestions compiled from review of multiple
studies8 in addition to personal experience, and may not reflect the dosages used in the selected reference. cReferences indicate selected publications
describing or supporting the use of the medication for the associated condition. Complete reference listings are provided in Supplementary Reference List 1
online. Abbreviations: b.i.d., twice daily; q.d., once daily; q.i.d., four times daily; t.i.d., three times daily.
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Competing interests
The authors declared that
they have no competing
interests.
THERAPEUTIC MANAGEMENT
The patient presenting with a late-onset progressive ataxic phenotype poses a diagnostic challenge to the clinician, which can be addressed
by means of a thorough medical history and