Co‐Occurrence of infantile epileptic seizures and childhood paroxysmal choreoathetosis in one family: Clinical, EEG, and SPECT characterization of episodic events

Abstract

The co-occurrence of infantile convulsions and childhood paroxysmal choreoathetosis (ICCA syndrome) has recently been reported in several families. The pattern of familial clustering observed is consistent with a single locus mutation which has been mapped onto the pericentromeric region of chromosome 16. We studied the main clinical, electroencephalogram (EEG), and single photon emission computed tomography (SPECT) characteristics of episodic events in a new family presenting clinical features similar to that described in the ICCA syndrome. In the first year of life, a mother and her two daughters suffered from rare afebrile seizures lasting from 30 seconds to 15 minutes. Ictal EEG recording in one daughter at 7 months of age showed bilateral polyspikes with a posterior predominance. In the three patients, epileptic seizures regressed within a few weeks, and never reoccurred. At the age of 7 and 12 years, respectively, the two daughters presented daily brief (20 seconds to 1 minute) involuntary choreoathetotic episodes. In 10 of these attacks, EEG did not show any epileptiform abnormalities. In both sisters, an ictal SPECT was performed during a choreoathetotic episode. Subtracting the ictal SPECT from the interictal SPECT coregistered to magnetic resonance imaging (MRI) revealed significant modifications in the local cerebral perfusion in the sensorimotor cortex, the supplementary motor areas, and pallidum. Carbamazepine completely suppressed paroxysmal dyskinesias. These observations, together with literature data, suggest that in this syndrome, depending on brain maturation, the same genetic abnormality may result in different paroxysmal neurological symptoms.

Increased interhemispheric resting-state functional connectivity in paroxysmal kinesigenic dyskinesia: A resting-state fMRI study

“…This provided us with further understanding of the pathophysiological mechanisms of PKD. In comparison with this, several other neuroimaging studies suggested abnormalities in other portions of the basal ganglia-thalamo-cortical circuitry in PKD, involving caudate nuclei [9], globus pallidus [12], thalamus [11,16,17]. This difference may be due to different imaging modalities, different state and relatively small sample sizes, indicating the underlying mechanisms may be rather complicated.…”

“…Homotopic RSFC has been demonstrated to display regional variation consistent with the brain's functional hierarchy [22], and exhibit regional and hierarchical specific development trajectories across the life span [24]. Considering that the hyperactivity and perfusion abnormalities in previous studies of PKD are mostly in bilateral homotopic regions [9,12,14], we speculated that interhemispheric connectivity abnormalities could exist. Here we utilized a recently validated approach -voxel-mirrored homotopic connectivity (VMHC) [24], which directly quantified the interhemispheric RSFC between each voxel in one hemisphere and its mirrored counterpart in the opposite hemisphere, to investigate alterations of interhemispheric RSFC in PKD.…”

“…Recently PRRT2 (proline-rich transmembrane protein 2) gene has been identified as a causative gene of PKD [5,6], but the exact role of this mutation is unknown [7,8]. Previous studies suggested abnormal ictal and interictal regional cerebral blood flow (CBF) in the basal ganglia, thalamus, sensorimotor cortex and premotor cortex in PKD [9][10][11][12][13]. Recent functional neuroimaging studies revealed increased amplitude of low frequency fluctuation (ALFF) in bilateral putamen and other cortical areas in the cortical-basal ganglia circuitry [14,15], which implies excessive spontaneous neural activity during resting state.…”

Genetics of infantile seizures with paroxysmal dyskinesia: the infantile convulsions and choreoathetosis (ICCA) and ICCA-related syndromes

“…EEG abnormalities have also been detected in a few patients with PD 19 20. The association of BIS with PD is particularly striking and has frequently been described in the same patients21 and in the same families 15 22 – 28. Less frequently, non-infantile epileptic seizures may also associate with PD; indeed, idiopathic generalised epilepsy,29 and in particular absence epilepsy,30 – 32 or even more complex epileptic phenotypes33 can be co-inherited with PD.…”

Differential Diagnosis of Chorea

“…Different loci on chromosome 16 have been identified. One syndrome termed "benign infantile convulsions and paroxysmal choreoathetosis" (ICCA) is associated with seizures, suggestive of a channelopathy [94].…”