Diagnosis and management of progressive ataxia in adults

Abstract

Progressive ataxia in adults can be difficult to diagnose, owing to its heterogeneity and the rarity of individual causes. Many patients remain undiagnosed ('idiopathic' ataxia). This paper provides suggested diagnostic pathways for the general neurologist, based on Ataxia UK's guidelines for professionals. MR brain scanning can provide diagnostic clues, as well as identify 'structural' causes such as tumours and multiple sclerosis. Advances in molecular genetics, including the wider and cheaper availability of 'next-generation sequencing', have enabled clinicians to identify many more cases with a genetic cause. Finally, autoimmunity is probably an under-recognised cause of progressive ataxia: as well as patients with antigliadin antibodies there are smaller numbers with various antibodies, including some associated with cancer. There are a few treatable ataxias, but also symptomatic treatments to help people with the spectrum of complications that might accompany progressive ataxias. Multidisciplinary team involvement and allied health professionals' input are critical to excellent patient care, including in the palliative phase. We can no longer justify a nihilistic approach to the management of ataxia.

Keywords: cerebellar disease; diagnosis and management; immunity; molecular genetics; progressive ataxia.

Figure 1

Fluid-attenuated inversion recovery (FLAIR) axial image of the brain, showing pontine and cerebellar atrophy, and ‘hot-cross bun’ sign, in a patient with multiple systems atrophy type C (MSA-C). Note the narrow middle cerebellar peduncles.

Figure 2

Axial T2-fluid-attenuated inversion recovery (FLAIR) image of the brain, showing high signal in the middle cerebellar peduncles, in a case of fragile X tremor-ataxia syndrome (FXTAS).

Figure 3

Axial T2-weighted MRI of the brain, showing haemosiderin deposition around the medulla and cerebellum, in a case of superficial siderosis. (Gradient echo (GRE)/T2* imaging would have demonstrated these changes more vividly.)

Figure 4

Axial T2-weighted MRI of the brain in a case of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) showing pontine hypointense (‘tigroid’) stripes.

Figure 5

Axial T2-weighted MRI of the brain in a case of hereditary spastic paraplegia 7 (SPG7) showing hyperintensity of the dentate nuclei (arrowed).

Figure 6

Sagittal T1-weighted MRI of the brain and upper cervical cord in a 26-year-old woman with ataxia. There is relative preservation of the brainstem and cerebellum, but thinning of upper cervical cord. (Friedreich’s ataxia (FRDA) was confirmed in her genetically.)

Figure 7

How often is a genetic cause of progressive ataxia identified? Dx, diagnosis; ANO10, ANO10-associated ataxia; AOA1/AOA2, ataxia with oculomotor apraxia types 1 and 2; AT, ataxia-telangiectasia; EA2, episodic ataxia type 2; FRDA, Friedreich’s ataxia; FXTAS, fragile X tremor-ataxia syndrome; Mit, mitochondrial cytopathy; SCA6, spinocerebellar ataxia type 6; SPG7, hereditary spastic paraplegia 7.

Figure 8

Infographic 1: The Diagnostic Pathway

Figure 9

Infographic 2: Symptom Management, including Multidisciplinary Team Input