Newly published in Neurology Genetics, a case study of a 51-year-old woman patient and 3 affected family members showed that paroxysmal ataxia/dysarthria occurred as an initial manifestation of a FGF14 repeat expansion, otherwise considered the root cause of spinocerebellar ataxia type 27B (SCA27B). This finding suggests that clinicians should test for FGF14 repeat expansion/SCA27B if a patient presents with paroxysmal dysarthria, especially if the paroxysmal attacks are associated with late-onset cerebellar ataxia or a family history consistent with a dominant disorder.1
In the case study, all 4 patients had paroxysmal ataxia/dysarthria occurring between 45 and 50 years of age as the initial manifestation of a FGF14 repeat expansion. A video of the initial patient showed 1 of her paroxysmal episodes triggered by either alcohol, coffee, exertion, emotion, or cigarette smoking. Notably, the initial patient’s mother developed permanent cerebellar manifestations at age 85 in addition to paroxysmal attacks.
Top Clinical Takeaways
- The study emphasized the importance of testing for SCA27B in patients with paroxysmal dysarthria, particularly if associated with late-onset cerebellar ataxia or a family history of dominant disorders.
- Paroxysmal ataxia in the family case study occurred between 45 and 50 years, triggered by various factors, with treatments like acetazolamide showing remarkable effectiveness in managing symptoms.
- Diagnostic tools, including brain MRI and video oculography eye tracking, can provide valuable insights into SCA27B, and the slow progression of the disease.
“The 4 members of the family reported here had paroxysmal ataxia as the initial manifestation of the disease, with an earlier onset compared with most patients reported in the literature,” senior author Emmanuel Roze, MD, PhD, professor of neurology at the Pierre et Marie Curie University in Paris; consultant neurologist and scientific researcher at the Brain and Spine Institute, Salpetriere Hospital in Paris, and colleagues wrote.1
READ MORE: Meta-Analysis Highlights Benefits of Noninvasive Brain Stimulation in Cerebellar Ataxia Care
The original patient was hospitalized at the University Hospitals Pitié Salpêtrière with a 6-year history of paroxysmal dysarthria-ataxia. The patient had episodes lasting between 10 minutes and 2 hours and were identified with dysarthria, gait ataxia, dizziness, and writing difficulties. The frequency of the episodes increased gradually over time up to 1 or 2 attacks per day. At the interictal examination, the patient had a normal score of 0 on the Scale for Assessment and Rating of Ataxia (SARA).
Investigators of the current study performed an ictal examination during a mild paroxysmal episode where the patient had a SARA score of 2. The patient revealed no signs of dysautonomia, especially no orthostatic hypotension or low urinary tract symptoms, and normal pallesthesia and reflexes. Additionally, a fluctuating “sensation of brain fog” in the absence of cognitive impairment was described by the patient.
In the MRI scan, the initial patient demonstrated slight cerebellar atrophy that predominated on the vermis. Authors noted that the oculography eye tracking revealed an asymptomatic low-amplitude downbeat nystagmus increased by head shaking maneuvers, increased square wave jerks, jerky pursuit with a downward predominance, and variable saccadic gain with a tendency to hypometria.
“Although SCA27B is not associated with a specific oculomotor profile, eye movement disorders are frequent, especially with a high prevalence of downbeat (as in our patient) or gaze-evoked nystagmus and diplopia. Of interest, interictal eye tracking in our index patient with paroxysmal ataxia revealed slight oculomotor abnormalities indicative of interictal cerebellar dysfunction and more specifically of a vestibulocerebellum impairment,” Roze et al noted.1 “Some patients have been reported to display associated sensory motor neuropathy ascertained by EMG, which was not found in our family. As observed in the patients of our family, the disease is of slow progression with a mean change of 0.2–0.4 points per year on the SARA scale, regardless of the clinical form of the disease and expansion size.”
Overall, the electromyogram and spinal cord MRI showed normal for the patient, and extensive workup that explored other causes of cerebellar syndrome reported negative. Notably, testing for FGF14 revealed an expanded allele greater than 450 repeats that was above the threshold considered to be abnormal.2-4 Authors also noted that treatment with acetazolamide 500 mg/d showed a significant decrease in the frequency and severity of attacks, and that 4-aminopyridine was not assessed.
“Brain MRI and video oculography eye tracking can provide additional diagnostic clues. This is important for clinical practice because treatments with acetazolamide or 4-aminopyridine can be remarkably effective in this context, at least for some patients,” Roze et al noted.1
1. Foucard C, Belley M, Sangare A, Bonnet C, Renaud M, Roze E. Paroxysmal Ataxia: A Characteristic Feature of FGF14 Repeat Expansion (SCA27B). Neurol Genet. 2023;10(1):e200118. Published 2023 Dec 8. doi:10.1212/NXG.0000000000200118
2. Pellerin D, Danzi MC, Wilke C, et al. Deep Intronic FGF14 GAA Repeat Expansion in Late-Onset Cerebellar Ataxia. N Engl J Med. 2023;388(2):128-141. doi:10.1056/NEJMoa2207406
3. Bonnet C, Pellerin D, Roth V, et al. Optimized testing strategy for the diagnosis of GAA-FGF14 ataxia/spinocerebellar ataxia 27B. Sci Rep. 2023;13(1):9737. Published 2023 Jun 15. doi:10.1038/s41598-023-36654-8
4. Hengel H, Pellerin D, Wilke C, et al. As Frequent as Polyglutamine Spinocerebellar Ataxias: SCA27B in a Large German Autosomal Dominant Ataxia Cohort. Mov Disord. 2023;38(8):1557-1558. doi:10.1002/mds.29559