Mesial temporal lobe epilepsy in a patient with spinocerebellar ataxia type 13 (SCA13)

Abstract

We report a female patient of German descent with a molecular diagnosis of SCA13 who presented with a history of cerebellar ataxia and epilepsy. The underlying mutation R420H had been shown to cause a dominant negative effect on the functional properties of the voltage-gated potassium channel KCNC3. Despite widespread KCNC3 expression in the central nervous system, the patient presented with a left mesiotemporal electroencephalogram focus and left hippocampal sclerosis. This is the first case, which reports an association between mesial temporal lobe epilepsy and spinocerebellar ataxia type 13. This demonstrates that epilepsy of structural-metabolic cause may be contingent upon genetically defined channelopathies.

Comprehensive Phenotype of the p.Arg420his Allelic Form of Spinocerebellar Ataxia Type 13

“…One individual was described similarly to the current cohort with a disease duration of approximately 20 years at age 43, cerebellar signs, ataxic gait, and clear progression of symptoms. A small kindred, one aged 66 years with onset at 42 years, and their offspring with a 3-year duration at age 31 years also shared cerebellar signs, gait ataxia, and disease progression but were also observed to have pyramidal signs and, in the younger subject, a seizure disorder [ 10 ]. This observation potentially extends the phenotype to include epilepsy, which has been described in the p.Arg423His allelic form of SCA13 [ 11 ].…”

Functional Analysis Helps to Define KCNC3 Mutational Spectrum in Dutch Ataxia Cases

“…It is sometimes accompanied by pyramidal signs, epilepsy, auditory deficits, and mild intellectual disability [1–5]. Disease onset varies from early childhood, with delayed motor and cognitive skills acquisition, to late-onset, but the course is always very slowly progressive.…”

Cerebellar Dysfunction and Ataxia in Patients with Epilepsy: Coincidence, Consequence, or Cause?

“… 100 Immune-mediated conditions Cerebellar ataxia and epilepsy with anti-GAD antibodies Adult-onset cerebellar syndrome, ataxia and stiffness, incontinence, retinal pathologies, seizures, and immunological co-morbidities 40 Celiac disease Neurological symptoms in up to 10% of cases, gastrointestinal symptoms preceding years of neurological symptoms, ataxia, myoclonus, tremor, seizures, abnormalities of eye movement 31 Hashimoto encephalopathy Antibodies to thyroperoxidase, cerebellar ataxia occurs in more than half of patients, diffuse encephalopathy with cognitive abnormalities, tremor, myoclonus, seizures and sleep disturbances acute to subacute with a rapid progression onset in all age groups more common in females than in males 90 , 101 Hereditary ataxias DRPLA Highest frequency in the Japanese population, age of onset 1–60 years (mean age 28,8), early onset: myoclonus, epilepsy and mental retardation, late onset: cerebellar ataxia, choreoathetosis and dementia, caused by a mutation in the ATN1 gene – increased CAG trinucleotide repeat. 102 , 103 SCA2 ATXN2 gene mutation, onset in the 3rd or 4th decade, truncal ataxia, dysarthria, slowed saccades and less commonly ophthalmoparesis and chorea or parkinsonism 104 , 105 SCA10 ATXN10 (E46L) gene mutation, onset from 18 to 45, slowly progressive cerebellar syndrome and epilepsy, sometimes mild pyramidal signs, peripheral neuropathy and neuropsychological disturbances 104 , 106 , 107 , 108 SCA13 KCNC3 gene mutation, onset in childhood, delayed motor and cognitive development followed by mild progression of cerebellar ataxia 41 , 104 , 108 SCA17 TBP gene mutation, dementia, psychiatric disorders, parkinsonism, dystonia, chorea, spasticity, and epilepsy …”

“…There was a case report of mesiotemporal epilepsy in an SCA13 patient and one of nocturnal frontal lobe epilepsy in an SCA17 patient. 41 , 42 There was also a description of epilepsy in patients with Friedreich ataxia. 43 A list of all possible conditions exceeds the scope of this article.…”