Early-Onset Cerebellar Ataxia With Retained Tendon Reflexes

Early onset cerebellar ataxia with retained reflexes (EOCARR) or Harding ataxia is a cerebellar ataxia characterized by the progressive association of a cerebellar and pyramidal syndrome with progressive cerebellar ataxia, brisk tendon reflexes, and sometimes profound sensory loss.

Epidemiology

The prevalence of EOCARR ataxia has been estimated to be around 1/100,000, and the birth prevalence at 1/48,000 births in North-western Italy.

Clinical description

EOCARR is a progressive cerebellar ataxia, with disease onset occurring in childhood or in juveniles (ranging from 3 to 20 years with a mean age of 9 years). EOCARR is characterized by dysarthria, gait ataxia, nystagmus, brisk tendon reflexes in the upper and lower limbs, absent ankle reflexes, and discrete or absent deep sensory loss. The association of brisk jerks and absent ankle reflexes may occur. Oculomotor disturbances, dysphagia, tremor, scoliosis, pes cavus, extensor plantar response, and lower limb wasting and weakness may be observed while amyotrophy is rarely observed. Moreover, spasticity may become progressively severe.

Etiology

The exact etiology of EOCARR is still unknown. However, molecular genetic analysis in a Tunisian family confirmed the genetic heterogeneity of this syndrome and mapped the gene locus to chromosome 13q11-12.

Diagnostic methods

Diagnosis relies on physical examination as well as on imaging findings (magnetic resonance imaging (MRI) or computed tomography (CT)) revealing cerebellar atrophy. Peripheral nerve conduction and nerve biopsy findings may show moderate to severe axonal sensory-motor neuropathy with axonal regeneration.

Differential diagnosis

Differential diagnosis includes Friedreich ataxia (FRDA; in contrast to EOCARR shows cardiomyopathy, diabetes mellitus, scoliosis, skeletal deformities or optic atrophy), autosomal dominant cerebellar ataxia (ADCA), autosomal recessive spastic ataxia of Charlevoix-Saguenay, ataxia with vitamin E deficiency (see these terms), and inherited metabolic disorders that may express ataxia.

Genetic counseling

Transmission is autosomal recessive. The parents of an affected child should be informed of the 25% risk of transmitting the disease to future offspring.

Management and treatment

Treatment is symptomatic, aimed towards the control of spasticity, and should include physiotherapy and pharmacotherapy (that may include spasmolytic drugs such as baclofen).

Prognosis

The period of latency before becoming wheelchair-bound is significantly longer in EOCARR than in FRDA, resulting in a better prognosis in patients with EOCARR than in those with FRDA.