Dentatorubral Pallidoluysian Atrophy

1. A D E W I J A Y A , M D – N O V E M B E R 2 0 2 3
Dentatorubral Pallidoluysian Atrophy

2. Outline
 Introduction
 Key clinical features
 Etiology
 Epidemiology
 Clinical features
 Evaluation
 Differential diagnosis
 Complications
 Treatment
 Consultations
 Prognosis
 Summary

3. Introduction
 DRPLA
 Autosomal dominant
 First described in 1946, and the name was given
in1958
Rocha Cabrero F, De Jesus O. Dentatorubral Pallidoluysian Atrophy. [Updated 2023 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-
. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560862/

4. Key Clinical Features
Choreoathetosis
Dystonia
Cognitive
impairment /
Demensia
Psychiatric
disturbance
Myoclonic epilepsy
Ataxia
Rocha Cabrero F, De Jesus O. Dentatorubral Pallidoluysian Atrophy. [Updated 2023 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-
. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560862/

5. Etiology
 Genetic
 Autosomal dominant
 Abnormal CAG repeat
Rocha Cabrero F, De Jesus O. Dentatorubral Pallidoluysian Atrophy. [Updated 2023 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-
. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560862/

6. Epidemiology
 Median age of onset of 31 years of age
 Female = male
 Asian predominant
 Juvenile vs Adult onset
Rocha Cabrero F, De Jesus O. Dentatorubral Pallidoluysian Atrophy. [Updated 2023 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-
. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560862/

7. Clinical Features
 Key clinical features
 Head tremor + optic atrophy
 Exam findings include
neurocognitive impairment on executive function,
language, memory, dysmetria, cerebellar ataxia,
motor weakness, upper motor neuron signs, and
difficulties with gait.
Rocha Cabrero F, De Jesus O. Dentatorubral Pallidoluysian Atrophy. [Updated 2023 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-
. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560862/

8. Evaluation
 Genetic testing
 EEG
 Brain MRI: diffuse cerebellar and brainstem atrophy,
diffuse periventricular white matter disease, but
these are mostly non-specific
 Hypoalbuminemia
Rocha Cabrero F, De Jesus O. Dentatorubral Pallidoluysian Atrophy. [Updated 2023 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-
. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560862/

9. Adult onset Juvenile onset
 Huntington disease
 Spinocerebellar ataxia
 Atypical parkinsonism
with cerebellar ataxia
 Alcohol
 Toxic/metabolic induced
ataxias
 Ataxic paraneoplastic
syndromes
 Familial essential myoclonus and
epilepsy
 Progressive myoclonic epilepsy
 Lafora disease
 Unverricht-Lundborg disease
 Infantile neuroaxonal dystrophy
 Neuroferritinopathy
 Myoclonus epilepsy associated with
ragged red fibers
 Heoxosaminidase A deficiency
 Neuronal ceroid-lipofuscinosis
 Gaucher disease
 Sialidosis
 Galactosialidosis
Differential Diagnosis
Carroll LS, Massey TH, Wardle M, Peall KJ. Dentatorubral-pallidoluysian Atrophy: An Update. Tremor Other Hyperkinet Mov (N Y). 2018;8:577.
Yoon WT, Youn J, Cho JW. Is cerebral white matter involvement helpful in the diagnosis of dentatorubral-pallidoluysian atrophy? J Neurol. 2012 Aug;259(8):1694-7.
Kobayashi J, Nagao M, Kawata A, Matsubara S. A case of late adult-onset dentatorubral-pallidoluysian atrophy mimicking central pontine myelinolysis. J Neurol. 2009 Aug;256(8):1369-71.

10. Complications
 Progressive repetitive seizures
 Status epilepticus
 SUDEP
 Solid/liquid dysphagia with potential aspiration
pneumonia
Hasegawa A, Ikeuchi T, Koike R, Matsubara N, Tsuchiya M, Nozaki H, Homma A, Idezuka J, Nishizawa M, Onodera O. Long-term disability and prognosis in dentatorubral-pallidoluysian
atrophy: a correlation with CAG repeat length. Mov Disord. 2010 Aug 15;25(11):1694-700.

11. Treatment
 No cure – supportive/symptomatic
 Seizure medications
 Drugs to treat movement disorders
 Amantadine/riluzole for ataxia
Rocha Cabrero F, De Jesus O. Dentatorubral Pallidoluysian Atrophy. [Updated 2023 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-
. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560862/

12. Consultations
 Adult or pediatric neurologists
 Epilepsy neurologists
 Geriatrics
 Pediatrics
 Geneticists
 Physical and occupational therapists
 Social workers
 Psychiatrists/psychologists
 Palliative medicine

13. Prognosis
 Median time from disease onset to death is 15 years
 Poor prognosis
 Functional impairment
Hasegawa A, Ikeuchi T, Koike R, Matsubara N, Tsuchiya M, Nozaki H, Homma A, Idezuka J, Nishizawa M, Onodera O. Long-term disability and prognosis in dentatorubral-pallidoluysian
atrophy: a correlation with CAG repeat length. Mov Disord. 2010 Aug 15;25(11):1694-700.

14. Summary
 Progressive, autosomal dominant CAG repeat disorder
typically characterized by ataxia, myoclonus, epilepsy,
choreoathetosis, dementia, psychiatric disturbance, and
progressive intellectual deterioration
 Juvenile vs adult onset
 Prognosis is poor, mean disease duration is about 15
years, and life expectancy is 8–16 years from symptom
onset
 Evaluation: genetic testing, EEG, brain MRI
 Treatment is predominantly supportive -
multidisciplinary

15. THANK YOU