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epileptiform sharp waves’173,174, ‘selective rates of maturation of the different cortical areas’57
and more recently of possible ‘neurobiological relationships’ between BCSSS and IGE84.

BCSSS, febrile and other idiopathic focal seizures in neonates and infants
One of the most interesting aspects of benign childhood seizures is their striking age-related
sequence that appears to reflect enhanced epileptogenicity of the developing brain, as a whole
and also of its functional systems, in different stages of maturation. Benign neonatal and
infantile seizures, rolandic epilepsy, PS, ICOE-G and other clinical phenotypes of BCSSS are
specific to early life and do not occur in adults. This is also the case with most febrile seizures
whose different genetic influences may explain their high prevalence amongst patients with
BCSSS and other more severe types of epilepsy, including the febrile plus phenotypes and
genotypes175,176. It appears that there are three main periods of age-related childhood
susceptibility to benign seizures: febrile, mainly generalised, convulsions first appear in early
childhood at a peak age of around 18–22 months; rolandic epilepsy and ICOE-G manifest with
purely focal seizures and occur in late childhood age; PS presents with mainly autonomic
seizures and covers the intermediate early childhood period with peak at four or five years. The
neonatal and early infantile periods are not immune to focal seizure susceptibility either, as
indicated by the benign neonatal seizures of the first few days of life177, and the benign infantile
focal seizures of Watanabe and Vigevano178. This point is exemplified by reports of children
with neonatal seizures who later developed rolandic epilepsy179 or PS5,77.

BCSSS, Landau–Kleffner syndrome, epilepsy with CSWS and atypical benign partial epilepsy

of childhood

Landau–Kleffner syndrome and epilepsy with CSWS180 are now considered by the ILAE as an
entity named ‘epileptic encephalopathy of CSWS including Landau–Kleffner syndrome’ with

a common pathophysiological mechanism1. Atypical benign partial epilepsy of childhood181,82
may be a mild form of epilepsy with CSWS183. Epileptic encephalopathy of CSWS including

Landau–Kleffner syndrome are functional disorders occurring at an age where cortical

synaptogenesis with abundant axonal sprouting and elemental functional network is being
established in the brain. Aggressive epileptogenic activity at this active period of brain
organisation is detrimental for the establishment of appropriate neuronal connections, normal
brain development and functioning184. All these disorders may constitute a rare and extreme
derailment of BCSSS. EEG manifests with abundant and often continuous high amplitude sharp
waves morphologically similar to the centrotemporal spikes and occipital paroxysms. Seizures
are predominantly nocturnal and often resemble rolandic seizures. Otherwise typical rolandic
epilepsy25, Panayiotopoulos syndrome117,118 evolve to clinical and EEG features of epileptic

encephalopathy of CSWS including Landau–Kleffner syndrome and atypical partial epilepsy

of childhood185. Atypical benign partial epilepsy of childhood probably is of intermediate
severity between the epileptic encephalopathy of CSWS and BCSSS. The reason for this
derailment of BCSSS is unknown, but may be related to location, epileptogenic threshold and
other intrinsic and external superimposed factors. Intense epileptic activity in the dominant

temporal region would affect linguistic capabilities as in Landau–Kleffner syndrome186.

Conversely, the mainly frontal localisation of CSWS primarily affects higher cognitive and
executive functioning184,187,188.

BCSSS and idiopathic generalised epilepsies
The majority of BCSSS if properly diagnosed do not have any clinical or EEG resemblance to
idiopathic generalised epilepsies though others may disagree84. Overlap of BCSSS with IGE is
limited (see above). However, a possible link, the type and extent of which should be explored
further with clinical and genetic studies may be suggested by:

(a) the occurrence of EEG generalised discharges in BCSSS (though these are markedly
different from the classical generalised spike or polyspike discharges of IGE) and