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Intra-individual seizure variability
The same child may have brief and lengthy seizures, diurnal and nocturnal, with marked,
inconspicuous, or even without any autonomic changes4,74-80,82. Even cardinal symptoms (such
as vomiting or eye deviation) may be present in one but absent in another seizure. Seizures
without autonomic manifestations are rare (7%) and occur in patients who also have additional
autonomic seizures4. Ictal video EEG recordings have documented that autonomic symptoms
and signs may vary between seizures of the same child93. There is no correlation between ictal
semiology and topography of inter-ictal spikes.

Aetiology
PS, like rolandic epilepsy, is probably genetically determined. Usually, there is no family
history of similar seizures, although siblings with PS or PS and rolandic epilepsy have been
reported74,77,79,80,97. There is a high prevalence of febrile seizures (about 17%)4.

SCN1A mutations have been recently reported in a child98 and two siblings97 with relatively
early onset of seizures, prolonged time over which many seizures have occurred and strong
association with febrile precipitants even after the age of five years. This is an area that needs
further attention but may indicate that SCN1A mutations contribute to a more severe phenotype
of PS.

Pathophysiology
Autonomic symptoms of any type are often encountered in seizures, whether focal or
generalised, in adults or children96,99,100. They are generated by activation or inhibition of parts
of the central autonomic network that involves the insular cortex, medial prefrontal cortex,
amygdala, hypothalamus, and ventrolateral medulla100. The resultant autonomic disturbances
depend on the brain areas involved in seizure onset or propagation, and appear as single or
multiple symptoms, some of which may be of localising value101.

In PS, the neuroanatomical and neurophysiological underpinnings of autonomic manifestations
are unknown. Any explanation of the pathophysiology of PS should take into account two
pieces of evidence that converge from clinical, EEG and magneto-encephalographic studies:
first, the epileptogenic zone in PS is wide and bilateral with multifocal pockets in cortical areas
surrounding major fissures such as calcarine, central or sylvian102-105; second, ictal autonomic
symptomatology appears to pertain to any epileptogenic cortical onset zone, be this occipital,
frontotemporal or frontal75,92-94,106.

Autonomic seizures and autonomic status epilepticus with the symptomatology and sequence
detailed in PS, appear to be specific for childhood96,107. For example, in adults ictal vomiting
occurs scarcely, and as a rule when consciousness is impaired following other focal mainly
temporal lobe symptoms, and is attributed to non-dominant mesial temporal lobe
involvement108-111. In contrast, ictal vomiting in children is common, usually occurs when
consciousness is intact without preceding focal cortical symptoms, and probably has no
localising or lateralising value (see Electroencephalography, below). A possible explanation for
these discrepancies may relate to the fact that children are constitutionally more vulnerable to
emetic disturbances as exemplified by the ‘cyclic vomiting syndrome’, a non-seizure disorder
of unknown aetiology that is also specific to childhood112 and associated with autonomic
dysfunction113. Thus, the preferential involvement of emetic and other autonomic
manifestations in PS may be attributed to a maturation-related susceptibility of the central
autonomic network4,107. This is compounded by a multifocal cortical epileptogenic
hyperexcitability that is also maturation related and may predominate in one brain area, which
is often posterior. It is likely that central autonomic networks have a lower threshold to
epileptogenic activation than those producing focal cortical semiology (occipital, frontal,
central, parietal and less often temporal). Irrespective of the localisation of their onset, ictal
discharges may activate the lower-threshold autonomic centres (and therefore produce