Neurophysiological study in a Spanish family with recessive spastic ataxia of Charlevoix‐Saguenay

Abstract

In order to characterize the electrodiagnostic features of autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) more fully, we report the clinical and neurophysiological findings in two patients from a Spanish pedigree with a homozygous missense point mutation in the SACS gene. Nerve conduction studies showed signs of both axonal and demyelinating neuropathy. In the upper-limb nerves, motor conduction velocity was intermediately slowed. Sensory nerve action potentials were attenuated or absent. In addition, slowed conduction in the central motor, somatosensory, and auditory brainstem pathways was observed, and masseter and blink reflexes were abnormal. As a whole, this constellation of electrophysiological findings helps in the diagnosis of ARSACS. Autosomal-recessive spastic ataxia of CharlevoixSaguenay (ARSACS) is a form of early-onset spastic ataxia that includes spasticity, cerebellar signs, and peripheral neuropathy due to mutation in the SACS gene. 3,11 Electrophysiological investigations of the disease are scanty and have revealed reduced motor conduction velocity (MCV), abolition of sensory nerve action potentials (SNAPs), and abnormal multimodality evoked potentials. 2 To better define electrodiagnostic features of this disorder, we report a detailed electrophysiological study in two ARSACS patients. CASE REPORTSClinical Findings. The two patients, a brother (patient 1) age 39 years, and sister (patient 2) age 28 years, were born from a healthy consanguineous pedigree. Both patients showed a similar clinical picture characterized by progressive gait imbalance since infancy. Examination of the cranial nerves revealed horizontal gaze-evoked nystagmus and saccadic pursuit with preservation of saccadic eye movements. Neither hypermyelinated retinal fibers nor ocular telangiectasias were found. There was a scanning dysarthria. In the limbs there was atrophy of foot and hand musculature (Fig. 1). Gait was ataxicspastic, but still possible without support. Mild distal weakness and hypopallesthesia in the lower limbs were noted. There was upper-limb and lower-limb ataxia. Tendon reflexes in the lower limbs were brisk, with ankle clonus and extensor plantar responses; upper-limb tendon reflexes were preserved and the jaw jerk was absent.As reported elsewhere and with informed consent, a homozygous missense mutation (7848CϾT) in the SACS gene was identified in both patients. 7 Routine laboratory investigations were normal and magnetic resonance imaging showed cerebellar and spinal cord atrophy in both patients.Neurophysiological Findings. Electromyography (EMG) of tibialis anterior muscle revealed a moderately reAbbreviations: ARSACS, autosomal-recessive spastic ataxia of Charlevoix-

Diagnostic Value of Neurophysiological Evaluation in Patients with ARSACS

“…The results of previous nerve conduction studies on ARSACS are summarized in Table 3 [6,9,11,12,[15][16][17][18][19][20][21][22][23]. Our findings along with those of previous studies, show that the electrophysiological features of peripheral neuropathy in ARSACS are the following: 1) a prolonged DML and reduced MCV with normal CMAPs in the upper-limb nerves, 2) absence Table 2 Results of nerve ultrasonographies in two patients with ARSACS.…”

Assessment of Whole-Brain White Matter by DTI in Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay

“…11,[21][22][23] Severe CST involvement, as assessed by motor-evoked potential abnormalities, was attributed to the demyelination of the CST in an autopsy study. 24 Our current TBSS study, on the contrary, points out both axonal and myelin damage in the CST. These features can also contribute to differentiation of ARSACS from other degenerative diseases of mainly axonal neuropathy, such as Friedreich ataxia.…”

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS): typical clinical and neuroimaging features in a Brazilian family

“…Lower limb peripheral neuropathy can also be detected later. Distal atrophy, pes cavus and hammer toes are commonly seen as the disease progresses 2,3,13 . In some patients, fundoscopy shows hypermyelination of fibers radiating from optic disc and embedding retinal vessels, a very peculiar finding 3 .…”