SCA2 presenting as an ataxia-parkinsonism-motor neuron disease syndrome

Apresentação clínica de SCA2 como uma síndrome ataxia-parkinsonismo-doença do neurônio motor

LETTERS

SCA2 presenting as an ataxia-parkinsonism-motor neuron disease syndrome

Apresentação clínica de SCA2 como uma síndrome ataxia-parkinsonismo-doença do neurônio motor

Pedro Braga-Neto; José Luiz Pedroso; André Carvalho Felício; Agessandro Abrahão; Lívia Almeida Dutra; Marcio Luiz Escorcio Bezerra; Orlando Graziani Povoas Barsottini

Department of Neurology and Neurosurgery, Division of General Neurology and Ataxias, Universidade Federal de São Paulo, São Paulo SP, Brazil

^{Correspondence}

The procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national). All subjects were provided with the approved informed consent.

Spinocerebellar ataxia type 2 (SCA2) is characterized by progressive cerebellar ataxia, slow saccadic eye movements and peripheral neuropathy. Atypical SCA2 phenotypes with prominent dementia, an amyotrophic lateral sclerosis-like presentation, and levodopa-responsive parkinsonism are also encountered¹.The definite diagnosis of SCA2 is based on clinical symptoms and molecular genetic testing to detect an abnormal CAG trinucleotide repeat expansion of the ATXN2 gene on chromosome 12q¹. The protein synthesized by ATXN2 is known as ataxin-2 that is involved in RNA metabolism and translation regulation¹.Herein we report an unusual case of SCA2 presenting as an ataxia-parkinsonism-motor neuron disease (MND) syndrome.

CASE

A 46-year-old Brazilian man of Italian ancestry, presented for consultation because of progressive gait instability and muscle cramps that started 18 months before. He also developed rapidly progressive muscle weakness few months before his first appointment. His family history revealed affected individuals (ataxia) within first and second generations. On neurological examination, there were mild dysarthria, slow saccades, mild limb and gait ataxia, parkinsonism, brisk reflexes and bilateral Babinski sign. He also presented muscle weakness in upper limbs, diffuse fasciculations and atrophy involving upper limbs, chest and face. Genetic testing confirmed the diagnosis of SCA2 with 40 CAG repeats. Brain magnetic resonance imaging (MRI) disclosed cerebellar and brainstem atrophy (Figure). Electroneuromyography showed denervation activity at rest, with fasciculation, fibrillation and positive sharp wave potentials in the bulbar, cervical, thoracic and lumbosacral regions. Nerve conduction studies showed normal sensory and motor nerve conduction velocities and reduced amplitudes of the motor potentials. We introduced riluzole 50 mg b.i.d. as treatment for amyotrophic lateral sclerosis (ALS).

DISCUSSION

Few previous studies have described the association of SCA2 with MND. Infante et al.² reported a case of a 61 years-old woman with SCA2 diagnosis who developed a levodopa-responsive parkinsonism after 6 months of the ataxia-onset of symptoms, but later on disease course presented MND syndrome².Recently, Nanetti et al.³ described another 66 year-old woman with SCA2 affected with progressive weakness and fasciculation³. Our patient was younger than the previous reports and presented MND disease shortly after SCA2 diagnosis.

In 2006, the 43-kDa TAR DNA binding protein (TDP-43) was identified as the major disease protein in ALS and frontotemporal lobar degeneration with ubiquinated inclusions⁴. Recently, Elden et al.⁵ pointed out to ATXN2 gene as a relatively common suitability gene to ALS. They demonstrated that ATXN2 is a potent modifier of TDP-43 toxicity in animal and cellular models. In addition, 6 patients with ALS were evaluated and disclosed different ATXN2 localization in spinal cord⁵.

This report highlights that unusual phenotypes such as an ataxia-parkinsonism-motor neuron disease syndrome may be found in SCA 2 individuals. This raises several questions such as whether or not patients investigating MND with or without known family members with cerebellar ataxia should be routinely screened for ATXN2. Future studies with larger series are welcome to address these questions.

Received 9 December 2010.

Accepted 2 February 2011.

• 1. Lastres-Becker I, Rüb U, Auburger G. Spinocerebellar ataxia 2 (SCA2). Cerebellum 2008;7:115-124.
• 2. Infante J, Berciano J, Volpini V, et al. Spinocerebellar ataxia type 2 with levodopa-responsive parkinsonism culminating in motor neuron disease. Mov Disord 2004;19:848-852.
• 3. Nanetti L, Fancellu R, Tomasello C, Gellera C, Pareyson D, Mariotti C. Rare association of motor neuron disease and spinocerebellar ataxia type 2 (SCA2): a new case and review of the literature. J Neurol 2009;256: 1926-1928.
• 4. Neumann M, Sampathu DM, Kwong LK, et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 2006;314:130-133.
• 5. Elden AC, Kim HJ, Hart MP, et al. Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS. Nature 2010;466:1069-1075.

Publication Dates

• Publication in this collection
  10 June 2011
• Date of issue
  2011