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patient hours of ECG recording were monitored, during which time 3377 seizures (1897
complex partial or secondarily generalised tonic-clonic seizures and 1480 simple partial
seizures) were reported by patients. Cardiac rhythm was captured on the implantable loop
recorders in 377 seizures. Ictal bradycardia was seen in 0.24% of all seizures over the study
period, and 2.1% of the recorded seizures. Seven of the 19 patients experienced ictal
bradycardia. Four of these had severe bradycardia or periods of asystole which led to the
insertion of a permanent pacemaker. Notably, only a small proportion of seizures for every
patient were associated with significant cardiac events despite identical seizure
characteristics59.

Extrapolation of ictal bradyarrhythmias to a mechanistic explanation for SUDEP remains
elusive. This is, at least partly, due to a lack of clinical evidence of common factors shared
by patients with ictal bradyarrhythmias and SUDEP and the difficulty in ascertaining the
importance of ictal bradyarrhythmias in SUDEP in relation to other proposed mechanisms,
including other intrinsic cardiac abnormalities or apnoea and hypoxia which may aggravate
arrhythmias.

Respiratory mechanisms
It is likely that primary respiratory dysfunction is involved in an important proportion of
SUDEP40,88-94. Alterations in respiration such as coughing, sighing, hyperventilation,
irregular breathing, apnoea, increased bronchial secretions, laryngospasm, respiratory arrest,
and neurogenic pulmonary oedema have all been described with seizures40,92,94-96. Some form
of respiratory compromise is commonly reported in witnessed cases of SUDEP97. Electrical
stimulation of multiple brain areas, particularly in limbic and temporal regions, has been
demonstrated to influence respiratory activity98,99, supporting the potential for seizures arising
from or involving these brain regions to alter respiratory function. Central apnoea can occur
secondary to the ictal discharge, acting at either the cortical or medullary level or possibly as
a result of secondary endogenous opioid release influencing the brainstem respiratory nuclei
directly. During post-ictal impairment of consciousness, hypercapnia and hypoxia may be
less potent respiratory stimuli.

In a study of 17 patients with epilepsy who underwent polysomnography with
cardiorespiratory monitoring in a supervised environment, ictal apnoea of greater than 10
seconds in duration was demonstrated in 20 out of 47 seizures. Oxyhaemoglobin saturation
decreased to less than 85% in 10 seizures. Central apnoea, which may evolve during a focal
or generalised seizure, was seen more frequently than obstructive apnoea, however the study
was in a controlled environment and assistance may have minimised the likelihood of
obstructive apneoa being observed40. Larger series have since expanded the descriptions of
hypoxaemia accompanying seizures100–102. Oxygen desaturations <90% are common,
occurring in approximately one-third of generalised and non-convulsive seizures100.
Significant desaturations have also been noted in limited electrographic seizures without clear
clinical accompaniments103. In a small number of cases (<5%), these desaturations may be
profound, with measured oxygen saturation (SaO2) <70%100. Interestingly, transient
bradycardia or sinus arrest has been seen in association with ictal apnoea suggesting that the
reported seizure-related arrhythmias may be consecutive to ictal apnoea40. Additional reports
of ictal apnoea are typically case studies recorded incidentally during video-EEG telemetry90-
92. In a study of 135 SUDEP cases, 15 of which were witnessed, observers described
respiratory difficulties, such as apnoea and obvious respiratory obstruction, in 12 patients,
although the conclusions that may be drawn are significantly limited by the quality of the
retrieved information and lack of additional relevant cardiorespiratory parameters93.
Witnesses have reported a delay between the seizure and time of death which is more
consistent with primary respiratory inhibition followed by respiratory arrest and the
development of hypoxia and pulmonary oedema, than ‘primary’ ictal cardiac asystole20. Peri-
ictal hypoxaemia has been associated with male gender, younger age in children,