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Review
. 2021 Jul;268(7):2493-2505.
doi: 10.1007/s00415-021-10415-x. Epub 2021 Feb 5.

The electrophysiological footprint of CACNA1A disorders

Elisabetta Indelicato  1 , Iris Unterberger  2 , Wolfgang Nachbauer  1 , Andreas Eigentler  1 , Matthias Amprosi  1 , Fiona Zeiner  3 , Edda Haberlandt  3   4 , Manuela Kaml  2 , Elke Gizewski  5 , Sylvia Boesch  6
Affiliations
Review

The electrophysiological footprint of CACNA1A disorders

Elisabetta Indelicato et al. J Neurol. 2021 Jul.

Abstract

Objectives: CACNA1A variants underlie three neurological disorders: familial hemiplegic migraine type 1 (FHM1), episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6). EEG is applied to study their episodic manifestations, but findings in the intervals did not gain attention up to date.

Methods: We analyzed repeated EEG recordings performed between 1994 and 2019 in a large cohort of genetically confirmed CACNA1A patients. EEG findings were compared with those of CACNA1A-negative phenocopies. A review of the related literature was performed.

Results: 85 EEG recordings from 38 patients (19 EA2, 14 FHM1, 5 SCA6) were analyzed. Baseline EEG was abnormal in 55% of cases (12 EA2, 9 FHM1). The most common finding was a lateralized intermittent slowing, mainly affecting the temporal region. Slowing was more pronounced after a recent attack but was consistently detected in the majority of patients also during the follow-up. Interictal epileptic discharges (IEDs) were detected in eight patients (7 EA2,1 FHM1). EEG abnormalities and especially IEDs were significantly associated with younger age at examination (16 ± 9 vs 43 ± 21 years in those without epileptic changes, p = 0.003) and with earlier onset of disease (1 (1-2) vs 12 (5-45) years, p = 0.0009). EEG findings in CACNA1A-negative phenocopies (n = 15) were largely unremarkable (p = 0.03 in the comparison with CACNA1A patients).

Conclusions: EEG abnormalities between attacks are highly prevalent in episodic CACNA1A disorders and especially associated with younger age at examination and earlier disease onset. Our findings underpin an age-dependent effect of CACNA1A variants, with a more severe impairment when P/Q channel dysfunction manifests early in life.

Keywords: Epilepsy; Episodic ataxia type 2; Familial hemiplegic migraine type 1; Intermittent epileptic discharges; Spinocerebellar ataxia type 6; Voltage-gated calcium channels.

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Conflict of interest statement

There are no competing interests related to the present work.

Figures

Fig. 1
Fig. 1
Bitemporal delta activity in Pt. 5-I. Bipolar longitudinal montage with 70 Hz filter and time constant of 0.3 s; sensitivity 7 μV
Fig. 2
Fig. 2
Superimposed bilateral occipital spikes in generalized rhythmic delta activity in Pt. 4-IV. Bipolar longitudinal montage with 70 Hz filter and time constant of 0.3 s; sensitivity 7 μV
Fig. 3
Fig. 3
Superimposed bilateral occipital spikes in generalized rhythmic delta activity in Pt. 4-VI. Bipolar longitudinal montage with 70 Hz filter and time constant of 0.3 s; sensitivity 10 μV
Fig. 4
Fig. 4
Superimposed bilateral occipital spikes in generalized rhythmic delta activity in Pt. 15-I. Bipolar longitudinal montage with 70 Hz filter and time constant of 0.3 s; sensitivity 10 μV
Fig. 5
Fig. 5
Left temporal sharp waves in Pt. 5-I. Bipolar longitudinal montage with 70 Hz filter and time constant of 0.3 s; sensitivity 7 μV
See this image and copyright information in PMC

References

    1. Rajakulendran S, Kaski D, Hanna MG. Neuronal P/Q-type calcium channel dysfunction in inherited disorders of the CNS. Nat Rev Neurol. 2012;8(2):86–96. - PubMed
    1. Epi KC. De Novo Mutations in SLC1A2 and CACNA1A are important causes of epileptic encephalopathies. Am J Hum Genet. 2016;99(2):287–298. - PMC - PubMed
    1. Ophoff RA, Terwindt GM, Vergouwe MN, van Eijk R, Oefner PJ, Hoffman SM, et al. Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell. 1996;87(3):543–552. - PubMed
    1. Jen J, Kim GW, Baloh RW. Clinical spectrum of episodic ataxia type 2. Neurology. 2004;62(1):17–22. - PubMed
    1. Ducros A, Denier C, Joutel A, Cecillon M, Lescoat C, Vahedi K, et al. The clinical spectrum of familial hemiplegic migraine associated with mutations in a neuronal calcium channel. N Engl J Med. 2001;345(1):17–24. - PubMed