LETTERS TO THE EDITOR
|Year : 2022 | Volume
| Issue : 4 | Page : 718-719
Muscle cramps profile among spinocerebellar ataxias
Gustavo Leite Franklin1, Carlos Henrique Ferreira Camargo2, Daniel Balaban3, João Matheus Marcon3, Salmo Raskin4, Alex Tiburtino Meira5, Hélio Afonso Ghizoni Teive6
1 Pontifícia Universidade Católica do Paraná, Curitiba, Brazil
2 Neurological Diseases Group, Graduate Program in Internal Medicine, Department of Internal Medicine, Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil
3 Federal University of Paraná, Curitiba, Brazil
4 Genetika – Centro de aconselhamento e laboratório de genética, Curitiba/PR, Brazil
5 Departamento de Medicina Interna, Universidade Federal da Paraíba, João Pessoa (PB), Brazil
6 Neurological Diseases Group, Graduate Program in Internal Medicine, Department of Internal Medicine, Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil; Federal University of Paraná, Curitiba, Brazil
|Date of Submission||26-Oct-2021|
|Date of Acceptance||18-Nov-2021|
|Date of Web Publication||05-Jan-2022|
Gustavo Leite Franklin
Rua Amazonas, 691/81 CEP 80610030
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Franklin GL, Ferreira Camargo CH, Balaban D, Marcon JM, Raskin S, Meira AT, Ghizoni Teive HA. Muscle cramps profile among spinocerebellar ataxias. Ann Indian Acad Neurol 2022;25:718-9
|How to cite this URL:|
Franklin GL, Ferreira Camargo CH, Balaban D, Marcon JM, Raskin S, Meira AT, Ghizoni Teive HA. Muscle cramps profile among spinocerebellar ataxias. Ann Indian Acad Neurol [serial online] 2022 [cited 2022 Oct 6];25:718-9. Available from: https://www.annalsofian.org/text.asp?2022/25/4/718/335001
Spinocerebellar ataxias (SCAs) constitute a heterogeneous group of neurodegenerative disorders, with an autosomal dominant inheritance. More than 40 different SCAs have already been identified, and SCA3, SCA2, and SCA1 are the most frequent types. The most common symptom is cerebellar ataxia, but other clinical manifestations may occur, suggesting a specific mutation that could further guide the genetic testing, such as “bulging-eyes” and upward gaze palsy in SCA3, seizures in SCA10, among others.,,
Muscle cramps, defined as a painful and sustained muscle contraction affecting a muscle or a group of muscles, are a prevalent non-motor symptom in specific SCA subtypes.,, Damage to the lower motor neuron is commonly implied, which causes collateral reinnervation giving rise to intramuscular nerve endings. Although some studies have associated muscle cramps to SCAs, there is no precise information about this symptom among the different types of SCAs.,,,,, In this way, the present study aimed to evaluate the prevalence of muscle cramps and their clinical aspects among the SCAs.
Sixty-eight patients, genetically diagnosed with SCA, were evaluated in the Ataxia Outpatient Clinic of Federal University of Paraná. Participants were divided in four groups according to their SCA subtype: Group 1-SCA2, Group 2-SCA3, Group 3-SCA10, Group 4 - “other”, which included patients with SCA1, SCA6 and dentatorubropallydoluysian atrophy (DRPLA). The Scale for Assessment and Rating of Ataxia (SARA) was used for evaluation of ataxia severity. Cramps were assessed by a questionnaire regarding patient's perception. Pain perception was evaluated using the visual analogue scale (VAS).
The Fischer exact test or Qui Square was used to compare qualitative variables. The t Student test was used to compare continuous variables with normal distribution, and the Mann-Whitney test and the Kruskal–Wallis test were applied to compare non-normal continuous variables. Spearman's coefficient was used for correlations. P values less than 5% were considered significant (p < 0.05).
All the 68 patients assessed were grouped in each of the following: Group 1 - SCA2 (n = 18; 22.8%), Group 2 - SCA3 (n = 24; 30.4%), Group 3 - SCA10 (n = 19; 24.0%), and Group 4 - “others” (n = 7; 8.9%) [Table 1]. The group “others” was composed by 5 SCA1 patients, 1 SCA6 patient and 1 DRPLA patient. Groups were similar regarding gender, age, disease duration and SARA score [Table 1].
Muscle cramps were present in all patients in the SCA2 group, in 17 patients (70.8%) in the SCA3 group, in 5 patients (26.3%) in the SCA10 group, and in 4 patients in group 4. The SCA2 group, when compared to the other groups (SCA2 vs. SCA3 [p = 0.014]; SCA2 vs. SCA10 [p = 0.0001]; SCA2 vs. “others” [p = 0.015]) showed a significantly higher frequency of muscle cramps. The SCA3 group had a significant higher frequency of muscle cramps compared to the SCA10 group [p = 0.0058] [Table 2].
When comparing the muscle cramps profile between the two most affected groups, SCA2 and SCA3, muscle cramps arose significantly earlier in SCA2 patients (29 ± 12.3 vs 43.2 ± 16.6, P =0.03). There was no difference between frequency, pain perception, duration and the quantity of affected muscle groups. The most affected muscle groups in the SCA2 group were lower limbs (94.4%), neck (44.4%), upper limbs (38.9%) and abdomen (33.3%). Among SCA3 patients the most affected sites were lower limbs (82.3%) and superior limbs (23.5%).
The time of muscle cramps tended to correlate with VAS in the SCA2 group (rho =0.562, P =0.056), but with no statistical significance. In both SCA2 and SCA3 groups, no correlation was found between muscle cramps frequency and disease duration (SCA2, rho = -.138, P =.583; SCA3, rho =.129, P =.621), frequency and muscle cramps duration (SCA2, rho =.297, P =.348; SCA3, rho =.113, P =.725) and quantity of muscle groups affected and SARA score (SCA2, rho = -.214, P =.424; SCA3, rho = -.093, P =.729).
Some studies have reported the prevalence of muscle cramps in SCA2, ranging from 6 to 81%., In our study, 100% of the SCA2 patients presented cramps. Also, it was found that muscle cramps tend to occur 8 years earlier in SCA2 compared to SCA3, and neck and abdomen cramps were characteristic of SCA2 patients. Our study is in accordance with previous studies, that described the beginning of the muscle cramps in SCA2, occurring 4 to 6.5 years before the ataxia's onset.,,,, In addition to being an early symptom in SCA2, cramps progress in frequency, duration and amount of muscles involved, as the disease progresses.
On the other hand, in SCA3 patients muscle cramps are more intense early in the disease course and tend to decrease severity as the muscular atrophy advances. In the present study, SCA3 muscle cramps affected primarily lower and upper limbs, in accordance with the literature. The correlation with greater tendency to statistical significance was the one between VAS and muscle cramp duration. In our study, we did not find any correlation between frequency, duration and quantity of muscles groups involved with disease duration. We did note, however, that muscle cramps occurred predominantly during nighttime and affected predominantly different muscle groups in SCA2 and SCA3 patients.
Previous research involving patients with SCA3 showed a frequency of muscle cramps of about 80%, a value similar to the one found in the present study. In SCA3, muscle cramps have been correlated to inferior motor neuron alterations, such as denervation and reinnervation recorded by electromyography. The main factor that determines when muscle cramps will occur is the size of CAG triplet repetition.
In conclusion, the present study found significant difference in muscle cramp frequency among SCAs, with high values in SCA2 and SCA3, being more frequent and presenting earlier in the first group. Muscle cramps arose before the ataxia in patients with SCA2 and SCA1, meanwhile patients with SCA3 showed after disease onset. These findings might allow a different approach during clinical investigation, although larger longitudinal studies are necessary to corroborate our findings.
We confirm that we have read the journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.
Declaration of patient consent
All patients included in this study gave written informed consent for the storage of their clinical data for research purposes.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Manto M-U. The wide spectrum of spinocerebellar ataxias (SCAs). Cerebellum 2005;4:2-6.
Franklin GL, Meira AT, Camargo CHF, Nascimento FA, Teive HAG. Upward gaze palsy: A valuable sign to distinguish spinocerebellar ataxias. Cerebellum. 2020;19:685-90.
Pedroso JL, França MC Jr, Braga-Neto P, D'Abreu A, Saraiva-Pereira ML, Saute JA, et al
. Nonmotor and extracerebellar features in Machado-Joseph disease: A review. Mov Disord 2013;28:1200-8.
Pedroso JL, Braga-Neto P, Escorcio-Bezerra ML, Abrahão A, Cristino de Albuquerque MV, Filho FMR, et al
. Non-motor and extracerebellar features in spinocerebellar ataxia type 2. Cerebellum 2017;16:34-9.
Kanai K, Kuwabara S, Arai K, Sung JY, Ogawara K, Hattori T. Muscle cramp in Machado Joseph disease-Altered motor axonal excitability properties and mexiletine treatment. Brain 2003;126:965-73.
Velázquez-Pérez L, Rodríguez-Labrada R, Canales-Ochoa N, Montero JM, Sánchez-Cruz G, Aguilera-Rodríguez R, et al
. Progression of early features of spinocerebellar ataxia type 2 in individuals at risk: A longitudinal study. Lancet Neurol 2014;13:482-9.
Globas C, du Montcel ST, Baliko L, Boesch S, Depondt C, DiDonato S, et al
. Early symptoms in spinocerebellar ataxia type 1, 2, 3, and 6. Mov Disord 2008;23:2232-8.
Jacobi H, Reetz K, du Montcel ST, Bauer P, Mariotti C, Nanetti L, et al
. Biological and clinical characteristics of individuals at risk for spinocerebellar ataxia types 1, 2, 3, and 6 in the longitudinal RISCA study: Analysis of baseline data. Lancet Neurol 2013;12:650-8.
Braga-Neto P, Godeiro-Junior C, Dutra LA, Pedroso JL, Barsottini OGP. Translation and validation into Brazilian version of the Scale of the assessment and rating of ataxia (SARA). Arq Neuropsiquiatr 2010;68:228-30.
Hawker GA, Mian S, Kendzerska T, French M. Measures of adult pain: Visual analog scale for pain (VAS pain), Numeric rating scale for pain (NRS pain), McGill pain questionnaire (MPQ), Short-form McGill pain questionnaire (SF-MPQ), Chronic pain grade scale (CPGS), short form-36 bodily pain scale. Arthritis Care Res 2011;63:S240-252.
[Table 1], [Table 2]