Machado-Joseph Disease Progressing to Truncal Dystonia

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Authors: Luiz Felipe Vasconcellos MSc, MD, José Luiz Pedroso MD, PhD and Orlando G.P. Barsottini MD, PhD

Article first published online: 22 AUG 2014 | DOI: 10.1002/mdc3.12052


Spinocerebellar ataxia type 3 (SCA3) or Machado-Joseph disease (MJD) is the most common autosomal dominant spinocerebellar ataxia (SCA) worldwide, and may present with a wide range of extra-cerebellar signs, resulted from a widespread central nervous system involvement.[1] Movement disorders in MJD includes both hypokinetic (parkinsonism) and hyperkinetic (dystonia, tremor, chorea and myoclonus). Dystonia is frequent in MJD, and may be focal, segmental or generalized.[2, 3] Herein, we describe a patient with MJD that presented with severe truncal dystonia resembling Pisa syndrome, a phenotype not yet described in this genetic condition.

A 64-year-old woman presented with slow progressive gait ataxia for the last 12 years. Family history was remarkable for undetermined ataxia. For the last 2 years, she developed low back pain and abnormal posture, with progressive worsening. Examination showed severe truncal dystonia, with prominent lateral flexion resembling Pisa syndrome (Fig. 1; see Video), besides mild ataxia, nystagmus, and bulging eyes. She was unable to correct the posture voluntarily in any position. There was no parkinsonism. The patient also had mild dysarthria and increased reflexes. Brain MRI disclosed moderate cerebellar atrophy. Spine CT scan showed scoliosis, presumably caused by the severe truncal dystonia. Spine MRI was unremarkable, except for scoliosis. The patient underwent electromyography (EMG) that ruled out stiff-person syndrome and confirmed dystonia in paraspinal and external oblique muscles. Electrodes were inserted in paraspinal (lumbar and thoracic) and abdominal oblique muscle. In this protocol, the patient was evaluated in the resting position (prone and standing positions) and in voluntary flexion of the trunk. Dystonia was confirmed by disclosing cocontraction of agonist and antagonist muscles evaluated with marked hyperactivity in left paraspinal and external oblique muscles. Genetic test confirmed Machado-Joseph disease (MJD; allele 1: 75 repeats; allele 2: 28 repeats—health subjects present from 12 to 44 repeats). The patient was treated with botulinun toxin (BoT), with poor response. There was no improvement with anticholinergic drugs and levodopa.

Truncal dystonia resembling Pisa syndrome in a patient with MJD.

Figure 1. Truncal dystonia resembling Pisa syndrome in a patient with MJD.

From 122 MJD patients followed in the Ataxia Unit at the Universidade Federal de São Paulo (São Paulo, Brazil) since 2008, and 24 from Instituto de Neurologia, Universidade Federal do Rio de Janeiro (Rio de Janeiro, Brazil) since 2010, this is the only patient with severe truncal dystonia resembling Pisa syndrome.

Patients with early onset of symptoms in MJD present a higher frequency of dystonia, which is also associated with larger CAG repeat expansions.[1-3] Interestingly, this patient had adult onset of ataxia symptoms, and this phenotype is usually characterized by ataxia and pyramidal signs, whereas dystonia is rare. Schmitz-Hubsch et al. studied a large number of patients with different SCA subtypes and observed dystonia in 23.9%.[4] But none had severe truncal dystonia such as in this case. In addition, the use of BoT has been shown to be extremely valuable for treating dystonia in MJD, particularly focal dystonia, except in our case.[1] Of note, some patients with MJD may have a clinical presentation that closely resembles dopamine-responsive dystonia with very mild cerebellar signs.[1, 3] Curiously, although several types of focal dystonia have been described in MJD, there is no report of severe truncal dystonia resembling Pisa syndrome in this degenerative condition.

Abnormal postures of the trunk are frequent features in basal ganglia disorders, particularly in Parkinson's disease (PD), and may include camptocormia, anterocollis, and Pisa syndrome. Camptocormia was ruled out because the patient had only mild anterior trunk flexion, and camptocormia is considered when patients have more than 45 degrees of anterior flexion. The phenomenology of our patient is most likely explained by Pisa syndrome, because there was a clear lateral flexion of the trunk, confirmed by EMG. We believe that scoliosis observed in our report was secondary to truncal dystonia, because other spine abnormalities were not found.

Pisa syndrome is an unusual truncal dystonia that might be related to neuroleptics and is also observed in multiple system atrophy, PD, and other neurodegenerative conditions.[5] The pathophysiology of Pisa syndrome is still not fully understood, and different mechanisms have been supposed, such as basal ganglia dysfunction, hyperactivity of paraspinal muscles, and even myopathy.[5] In PD, some data have demonstrated that pathophysiological mechanisms related to Pisa syndrome include hyperactivity of lumbar paraspinal muscles.[6] In line with PD, brain imaging and neuropathological studies in MJD patients have disclosed basal ganglia and SN degeneration as well as dysfunction in the dopaminergic pathway.[1, 7, 8] These pathological findings are the most likely explanations presumed to be the anatomical basis for the constellation of movement disorders found in MJD, also including abnormal postures of the trunk and Pisa syndrome. Moreover, similarly to observed by Tinazzi et al. in PD, we found marked hyperactivity of paraspinal muscles in our patient.

We suggest that severe truncal dystonia, particularly with lateral flexion (Pisa syndrome), must be included in the movement disorders and abnormal postures observed in MJD patients. Also, based on this single case description, truncal dystonia in MJD seems to have poor response to BoT, anticholinergic drugs, or l-dopa.



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