Panayiotopoulos syndrome
Encyclopedia
Panayiotopoulos syndrome is a common idiopathic
childhood-related seizure disorder that occurs exclusively in otherwise normal children (idiopathic epilepsy) and manifests mainly with autonomic epileptic seizures and autonomic status epilepticus
. An expert consensus has defined Panayiotopoulos syndrome as "a benign age-related focal seizure disorder occurring in early and mid-childhood. It is characterized by seizures, often prolonged, with predominantly autonomic symptoms, and by an EEG
[electroencephalogram] that shows shifting and/or multiple foci, often with occipital predominance."
for this syndrome in the new International League against Epilepsy report on classification, which abandoned a number of previously used descriptive terms such as early onset benign childhood epilepsy with occipital paroxysms, early onset benign childhood occipital epilepsy, nocturnal childhood occipital epilepsy. The reason for this is that these descriptive terms were criticized as incorrect because in Panayiotopoulos syndrome:
(1) Onset of seizures is mainly with autonomic symptoms, which are not occipital lobe
manifestations.
(2) Of occipital symptoms, only deviation of the eyes may originate from the occipital regions, but this rarely occurs at onset. Visual symptoms are exceptional and not consistent in recurrent seizures.
(3) Interictal occipital spikes may never occur.
(4) Magnetoencephalography
may show equivalent current dipole
s clustering in the frontal areas.
(5) Ictal EEG has documented variable onset from the posterior or anterior regions
described this syndrome and autonomic status epilepticus particular to childhood through a 30-year prospective study that started in Greece
in 1975. Initial publications included patients with EEG occipital paroxysms or occipital spikes that attracted the main attention, but later it became apparent that the same clinical manifestations, and mainly ictal vomiting
, could occur in children with EEG extraoccipital spikes or normal EEG.
In Panayiotopoulos’ original study, ictal vomiting occurred in only 24 children out of 900 patients of all ages with epileptic seizures. Twenty-one were otherwise normal children (idiopathic cases constituting what is now considered Panayiotopoulos syndrome), and 3 had symptomatic epilepsies. Half of the seizures were lengthy, lasting for hours (autonomic status epilepticus). The EEG of the 21 idiopathic cases showed great variations: 12 had occipital paroxysms or spikes alone or with extraoccipital spikes; 2 had central spikes and giant somatosensory
evoked spikes; 2 had midline spikes; 1 had frontal spikes; 1 had brief generalized discharges; and 3 had consistently normal EEG. Subsequent attention was focused on the predominant group with occipital spikes, which was established as “early onset benign childhood epilepsy with occipital paroxysms”. The other group of 9 children with extraoccipital spikes or normal EEGs was reevaluated much later; their clinical manifestations and outcome were similar to those patients with occipital spikes. Based on these results, it has been concluded that these 21 children, despite different EEG manifestations, suffered from the same disease, which is now designated as Panayiotopoulos syndrome to incorporate all cases irrespective of EEG localizations.
However, there was initial scepticism and resistance to these findings, including from influential epileptologist
s because as explained by Ferrie and Livingston:“(a) ictal vomiting had been considered as extremely rare and hitherto had been mainly described in neurosurgical series of adult patients. In children it was generally not considered as having an epileptic origin; (b) autonomic status epilepticus was not recognised as a diagnostic entity; the proposition that it might be a common occurrence in a benign seizure disorder challenged orthodox concepts of status epilepticus; (c) it implied that paediatricians had been failing to diagnose significant numbers of children with epilepsy, instead erroneously labeling then as having diverse non-epileptic disorders such as encephalitis
, syncope
, migraine
, cyclic vomiting syndrome
and gastroenteritis
; (d) the characteristic EEG findings suggested alternative diagnoses. Occipital spikes suggested “childhood epilepsy with occipital paroxysms” of Gastaut; multifocal spikes suggested symptomatic epilepsies with poor prognosis
.
The veracity of Panayiotopoulos’s initial descriptions has, over the last two decades, been confirmed in large and long term studies from Europe
, Japan
and South America
. The published database on which our knowledge of PS is now based includes over 800 cases of all races; there are few epilepsy syndromes which are better characterised.”What emerges are a remarkably uniform clinical picture and a diagnosis which is strikingly useful in helping predict prognosis and dictate management.”
Autonomic status epilepticus is the more common type of nonfebrile status epilepticus in otherwise normal children and has been assessed in a consensus statement.
, retching
and vomiting as predominant symptoms. Other autonomic manifestations include pallor
(or, less often, flushing
or cyanosis
), mydriasis
(or, less often, miosis
), cardiorespiratory and thermoregulatory
alterations, incontinence of urine
and/or feces, hypersalivation
, and modifications of intestinal motility. In approximately one fifth of the seizures the child becomes unresponsive and flaccid (ictal syncope) before or often without convulsion
s. Syncopal-like attacks (ictal syncope) with the child becoming “completely unresponsive and flaccid like a rag doll” occur in one fifth of the seizures. Cardiorespiratory arrest is exceptional. More-conventional seizure symptoms often appear after the onset of autonomic manifestations. The child, who was initially fully conscious, becomes confused and unresponsive. Eyes turn to one side or gaze widely open. Only half of the seizures end with brief hemiconvulsions or generalized convulsions. Autonomic symptoms may be the only features of the seizures. None of the above symptoms alone is a prerequisite for diagnosis
. Recurrent seizures may not be stereotype
d. The same child may have brief or prolonged seizures and autonomic manifestations may be severe or inconspicuous.
Most of the seizures are prolonged and half of them last more than 30 minutes thus constituting autonomic status epilepticus, which is the more common nonconvulsive status epilepticus in normal children. Characteristically, even after the most severe seizures and ASE, the child is normal after a few hours of sleep
, which is both diagnostic and reassuring.
Seizures can occur at any time but they are more common during sleep.
is the only investigation with abnormal results, usually showing multiple spikes in various brain locations. There is marked variability of interictal EEG findings from normal to multifocal spikes that also change significantly in serial EEGs. Occipital spikes are common but not necessary for diagnosis. Frontal or centrotemporal spikes may be the only abnormality. Generalised discharges may happen alone or together with focal spikes. A few children have consistently normal EEG, including sleep EEG. EEG abnormalities may persist for many years after clinical remission
. Conversely, spikes may appear only once in successive EEGs. Series of EEGs of the same child may present with all of the above variations from normal to very abnormal. EEG abnormalities do not appear to determine clinical manifestations, duration, severity, and frequency of seizures or prognosis.
There are now significant reports of ictal EEGs, which objectively document the seizures of Panayiotopoulos syndrome and their variable localisation at onset.
or, less common, Panayiotopoulos syndrome and idiopathic childhood occipital epilepsy of Gastaut have been reported. There is a high prevalence of febrile seizure
s (about 17%).
SCN1A mutation
s have been reported in a child and in 2 siblings with relatively early onset of seizures, prolonged time over which many seizures have occurred, and strong association of seizures with febrile precipitants even after the age of 5 years. However, no such mutations were found in another couple of siblings and homozygous twin
s with typical Panayiotopoulos syndrome and no febrile seizure precipitants. These data indicate that SCN1A mutations when found contribute to a more severe clinical phenotype
of Panayiotopoulos syndrome.
Panayiotopoulos syndrome and all other benign childhood focal seizures, with rolandic epilepsy as their main representative, are probably linked due to a common, genetically-determined, mild, and reversible functional derangement of the brain cortical maturational process that Panayiotopoulos proposed as "benign childhood seizure susceptibility syndrome". The various EEG and seizure manifestations often follow an age- (maturation-) related localization. Panayiotopoulos syndrome is probably the early onset phenotype of the benign childhood seizure susceptibility syndrome.
During a recorded autonomic seizure, there was a small increase in blood pressure
(+5/4 mm Hg, systolic/diastolic), pronounced increases in heart rate
(+59 bpm) and plasma concentrations of norepinephrine
(+242 pg/mL), epinephrine (+175 pg/mL), and vasopressin
(+22.1 pg/mL); serum glucose was also elevated (206 mg/dL). The significant increase in plasma vasopressin may explain the emetic autonomic symptoms.
, syncope
, migraine
, cyclic vomiting syndrome
, motion sickness
, sleep disorder
, or gastroenteritis
. The consequence is avoidable misdiagnosis, high morbidity, and costly mismanagement.
Formal neuropsychological assessment of children with Panayiotopoulos syndrome showed that these children have normal IQ and they are not on any significant risk of developing cognitive and behavioural aberrations, which when they occur they are usually mild reversible. Prognosis of cognitive function is good even for patients with atypical evolutions.
However, though PS is benign in terms of its evolution, autonomic seizures are potentially life threatening in the rare context of cardiorespiratory arrest.
Autonomic status epilepticus in the acute stage needs thorough evaluation for proper diagnosis and assessment of the neurologic/autonomic state of the child. “Rescue” benzodiazepine
s are commonly used to terminate it. Aggressive treatment should be avoided because of the risk of iatrogenic
complications, including cardiovascular arrest. There is some anecdotal concern that intravenous lorazepam
and/or diazepam
may precipitate cardiovascular arrest. Early parental treatment is more effective than late emergency treatment. Buccal midazolam
is probably the first choice medication for out of hospital termination of autonomic status epilepticus which should be administered as soon as the child shows evidence of onset of its habitual autonomic seizures.
Parental education about PS is the cornerstone of correct management. The traumatizing, sometimes long-lasting effect on parents is significant particularly because autonomic seizures may last for many hours compounded by physicians’ uncertainty regarding diagnosis, management, and prognosis.
Idiopathic
Idiopathic is an adjective used primarily in medicine meaning arising spontaneously or from an obscure or unknown cause. From Greek ἴδιος, idios + πάθος, pathos , it means approximately "a disease of its own kind". It is technically a term from nosology, the classification of disease...
childhood-related seizure disorder that occurs exclusively in otherwise normal children (idiopathic epilepsy) and manifests mainly with autonomic epileptic seizures and autonomic status epilepticus
Status epilepticus
Status epilepticus is a life-threatening condition in which the brain is in a state of persistent seizure. Definitions vary, but traditionally it is defined as one continuous unremitting seizure lasting longer than 5 minutes, or recurrent seizures without regaining consciousness between seizures...
. An expert consensus has defined Panayiotopoulos syndrome as "a benign age-related focal seizure disorder occurring in early and mid-childhood. It is characterized by seizures, often prolonged, with predominantly autonomic symptoms, and by an EEG
EEG
EEG commonly refers to electroencephalography, a measurement of the electrical activity of the brain.EEG may also refer to:* Emperor Entertainment Group, a Hong Kong-based entertainment company...
[electroencephalogram] that shows shifting and/or multiple foci, often with occipital predominance."
Classification and nomenclature
Panayiotopoulos syndrome is now the formally approved nomenclatureNomenclature
Nomenclature is a term that applies to either a list of names or terms, or to the system of principles, procedures and terms related to naming - which is the assigning of a word or phrase to a particular object or property...
for this syndrome in the new International League against Epilepsy report on classification, which abandoned a number of previously used descriptive terms such as early onset benign childhood epilepsy with occipital paroxysms, early onset benign childhood occipital epilepsy, nocturnal childhood occipital epilepsy. The reason for this is that these descriptive terms were criticized as incorrect because in Panayiotopoulos syndrome:
(1) Onset of seizures is mainly with autonomic symptoms, which are not occipital lobe
Occipital lobe
The occipital lobe is the visual processing center of the mammalian brain containing most of the anatomical region of the visual cortex. The primary visual cortex is Brodmann area 17, commonly called V1...
manifestations.
(2) Of occipital symptoms, only deviation of the eyes may originate from the occipital regions, but this rarely occurs at onset. Visual symptoms are exceptional and not consistent in recurrent seizures.
(3) Interictal occipital spikes may never occur.
(4) Magnetoencephalography
Magnetoencephalography
Magnetoencephalography is a technique for mapping brain activity by recording magnetic fields produced by electrical currents occurring naturally in the brain, using arrays of SQUIDs...
may show equivalent current dipole
Dipole
In physics, there are several kinds of dipoles:*An electric dipole is a separation of positive and negative charges. The simplest example of this is a pair of electric charges of equal magnitude but opposite sign, separated by some distance. A permanent electric dipole is called an electret.*A...
s clustering in the frontal areas.
(5) Ictal EEG has documented variable onset from the posterior or anterior regions
History
Chrysostomos (Tomis) P. PanayiotopoulosChrysostomos P. Panayiotopoulos
Chrysostomos P. Panayiotopoulos MD, PhD, FRCP is a renowned expert in the field of the epilepsies. Panayiotopoulos syndrome is named after him....
described this syndrome and autonomic status epilepticus particular to childhood through a 30-year prospective study that started in Greece
Greece
Greece , officially the Hellenic Republic , and historically Hellas or the Republic of Greece in English, is a country in southeastern Europe....
in 1975. Initial publications included patients with EEG occipital paroxysms or occipital spikes that attracted the main attention, but later it became apparent that the same clinical manifestations, and mainly ictal vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
, could occur in children with EEG extraoccipital spikes or normal EEG.
In Panayiotopoulos’ original study, ictal vomiting occurred in only 24 children out of 900 patients of all ages with epileptic seizures. Twenty-one were otherwise normal children (idiopathic cases constituting what is now considered Panayiotopoulos syndrome), and 3 had symptomatic epilepsies. Half of the seizures were lengthy, lasting for hours (autonomic status epilepticus). The EEG of the 21 idiopathic cases showed great variations: 12 had occipital paroxysms or spikes alone or with extraoccipital spikes; 2 had central spikes and giant somatosensory
Somatosensory system
The somatosensory system is a diverse sensory system composed of the receptors and processing centres to produce the sensory modalities such as touch, temperature, proprioception , and nociception . The sensory receptors cover the skin and epithelia, skeletal muscles, bones and joints, internal...
evoked spikes; 2 had midline spikes; 1 had frontal spikes; 1 had brief generalized discharges; and 3 had consistently normal EEG. Subsequent attention was focused on the predominant group with occipital spikes, which was established as “early onset benign childhood epilepsy with occipital paroxysms”. The other group of 9 children with extraoccipital spikes or normal EEGs was reevaluated much later; their clinical manifestations and outcome were similar to those patients with occipital spikes. Based on these results, it has been concluded that these 21 children, despite different EEG manifestations, suffered from the same disease, which is now designated as Panayiotopoulos syndrome to incorporate all cases irrespective of EEG localizations.
However, there was initial scepticism and resistance to these findings, including from influential epileptologist
Epileptologist
An epileptologist is a neurologist who specializes in the treatment of epilepsy. Epileptologists are experts in seizures and seizure disorers, anticonvulsants, and special situations involving seizures, such as cases in which all treatment intended to stop seizures has failed and epilepsy in...
s because as explained by Ferrie and Livingston:“(a) ictal vomiting had been considered as extremely rare and hitherto had been mainly described in neurosurgical series of adult patients. In children it was generally not considered as having an epileptic origin; (b) autonomic status epilepticus was not recognised as a diagnostic entity; the proposition that it might be a common occurrence in a benign seizure disorder challenged orthodox concepts of status epilepticus; (c) it implied that paediatricians had been failing to diagnose significant numbers of children with epilepsy, instead erroneously labeling then as having diverse non-epileptic disorders such as encephalitis
Encephalitis
Encephalitis is an acute inflammation of the brain. Encephalitis with meningitis is known as meningoencephalitis. Symptoms include headache, fever, confusion, drowsiness, and fatigue...
, syncope
Syncope
In phonology, syncope is the loss of one or more sounds from the interior of a word; especially, the loss of an unstressed vowel. It is found bothin Synchronic analysis of languages and Diachronics .-Found synchronically:...
, migraine
Migraine
Migraine is a chronic neurological disorder characterized by moderate to severe headaches, and nausea...
, cyclic vomiting syndrome
Cyclic vomiting syndrome
Cyclic vomiting syndrome or cyclical vomiting syndrome is a condition whose symptoms are recurring attacks of intense nausea, vomiting and sometimes abdominal pain and/or headaches or migraines...
and gastroenteritis
Gastroenteritis
Gastroenteritis is marked by severe inflammation of the gastrointestinal tract involving both the stomach and small intestine resulting in acute diarrhea and vomiting. It can be transferred by contact with contaminated food and water...
; (d) the characteristic EEG findings suggested alternative diagnoses. Occipital spikes suggested “childhood epilepsy with occipital paroxysms” of Gastaut; multifocal spikes suggested symptomatic epilepsies with poor prognosis
Prognosis
Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...
.
The veracity of Panayiotopoulos’s initial descriptions has, over the last two decades, been confirmed in large and long term studies from Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...
, Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
and South America
South America
South America is a continent situated in the Western Hemisphere, mostly in the Southern Hemisphere, with a relatively small portion in the Northern Hemisphere. The continent is also considered a subcontinent of the Americas. It is bordered on the west by the Pacific Ocean and on the north and east...
. The published database on which our knowledge of PS is now based includes over 800 cases of all races; there are few epilepsy syndromes which are better characterised.”What emerges are a remarkably uniform clinical picture and a diagnosis which is strikingly useful in helping predict prognosis and dictate management.”
Autonomic status epilepticus is the more common type of nonfebrile status epilepticus in otherwise normal children and has been assessed in a consensus statement.
Epidemiology
Panayiotopoulos syndrome probably affects 13% of children aged 3 to 6 years who have had 1 or more afebrile seizures and 6% of such children in the 1- to 15-year age group. All races are affected.Clinical Features
Panayiotopoulos syndrome occurs exclusively in otherwise normal children and manifests mainly with infrequent autonomic epileptic seizures and autonomic status epilepticus. Onset of seizures is from age 1 to 14 years with 76% starting between 3–6 years. Autonomic seizures consist of episodes of disturbed autonomic function with nauseaNausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
, retching
Retching
Retching is a process in the human body where gastric contents are forced into the esophagus but do not enter the pharynx. Retching usually precedes vomiting, when the upper esophageal sphincter remains closed. If the upper esophageal sphincter is open, vomiting occurs. It can also be caused by a...
and vomiting as predominant symptoms. Other autonomic manifestations include pallor
Pallor
Pallor is a reduced amount of oxyhaemoglobin in skin or mucous membrane, a pale color which can be caused by illness, emotional shock or stress, stimulant use, lack of exposure to sunlight, anaemia or genetics....
(or, less often, flushing
Flushing (physiology)
For a person to flush is to become markedly red in the face and often other areas of the skin, from various physiological conditions. Flushing is generally distinguished, despite a close physiological relation between them, from blushing, which is milder, generally restricted to the face, cheeks or...
or cyanosis
Cyanosis
Cyanosis is the appearance of a blue or purple coloration of the skin or mucous membranes due to the tissues near the skin surface being low on oxygen. The onset of cyanosis is 2.5 g/dL of deoxyhemoglobin. The bluish color is more readily apparent in those with high hemoglobin counts than it is...
), mydriasis
Mydriasis
Mydriasis is a dilation of the pupil due to disease, trauma or the use of drugs. Normally, the pupil dilates in the dark and constricts in the light to respectively improve vividity at night and to protect the retina from sunlight damage during the day...
(or, less often, miosis
Miosis
Miosis is the constriction of the pupil of the eye to two millimeters or less...
), cardiorespiratory and thermoregulatory
Thermoregulation
Thermoregulation is the ability of an organism to keep its body temperature within certain boundaries, even when the surrounding temperature is very different...
alterations, incontinence of urine
Urinary incontinence
Urinary incontinence is any involuntary leakage of urine. It is a common and distressing problem, which may have a profound impact on quality of life. Urinary incontinence almost always results from an underlying treatable medical condition but is under-reported to medical practitioners...
and/or feces, hypersalivation
Hypersalivation
Hypersalivation is excessive production of saliva. It has also been defined as increased amount of saliva in the mouth, which may also be caused by decreased clearance of saliva....
, and modifications of intestinal motility. In approximately one fifth of the seizures the child becomes unresponsive and flaccid (ictal syncope) before or often without convulsion
Convulsion
A convulsion is a medical condition where body muscles contract and relax rapidly and repeatedly, resulting in an uncontrolled shaking of the body. Because a convulsion is often a symptom of an epileptic seizure, the term convulsion is sometimes used as a synonym for seizure...
s. Syncopal-like attacks (ictal syncope) with the child becoming “completely unresponsive and flaccid like a rag doll” occur in one fifth of the seizures. Cardiorespiratory arrest is exceptional. More-conventional seizure symptoms often appear after the onset of autonomic manifestations. The child, who was initially fully conscious, becomes confused and unresponsive. Eyes turn to one side or gaze widely open. Only half of the seizures end with brief hemiconvulsions or generalized convulsions. Autonomic symptoms may be the only features of the seizures. None of the above symptoms alone is a prerequisite for diagnosis
Diagnosis
Diagnosis is the identification of the nature and cause of anything. Diagnosis is used in many different disciplines with variations in the use of logics, analytics, and experience to determine the cause and effect relationships...
. Recurrent seizures may not be stereotype
Stereotype
A stereotype is a popular belief about specific social groups or types of individuals. The concepts of "stereotype" and "prejudice" are often confused with many other different meanings...
d. The same child may have brief or prolonged seizures and autonomic manifestations may be severe or inconspicuous.
Most of the seizures are prolonged and half of them last more than 30 minutes thus constituting autonomic status epilepticus, which is the more common nonconvulsive status epilepticus in normal children. Characteristically, even after the most severe seizures and ASE, the child is normal after a few hours of sleep
Sleep
Sleep is a naturally recurring state characterized by reduced or absent consciousness, relatively suspended sensory activity, and inactivity of nearly all voluntary muscles. It is distinguished from quiet wakefulness by a decreased ability to react to stimuli, and is more easily reversible than...
, which is both diagnostic and reassuring.
Seizures can occur at any time but they are more common during sleep.
Diagnostic tests
An EEG (electroencephalogram)Electroencephalography
Electroencephalography is the recording of electrical activity along the scalp. EEG measures voltage fluctuations resulting from ionic current flows within the neurons of the brain...
is the only investigation with abnormal results, usually showing multiple spikes in various brain locations. There is marked variability of interictal EEG findings from normal to multifocal spikes that also change significantly in serial EEGs. Occipital spikes are common but not necessary for diagnosis. Frontal or centrotemporal spikes may be the only abnormality. Generalised discharges may happen alone or together with focal spikes. A few children have consistently normal EEG, including sleep EEG. EEG abnormalities may persist for many years after clinical remission
Remission
Remission may refer to:*Remission , the state of absence of disease activity in patients with a chronic illness, with the possibility of return of disease activity*Remission , the reflection or scattering of light by a material...
. Conversely, spikes may appear only once in successive EEGs. Series of EEGs of the same child may present with all of the above variations from normal to very abnormal. EEG abnormalities do not appear to determine clinical manifestations, duration, severity, and frequency of seizures or prognosis.
There are now significant reports of ictal EEGs, which objectively document the seizures of Panayiotopoulos syndrome and their variable localisation at onset.
Etiology
Panayiotopoulos syndrome is probably genetically determined, though conventional genetic influences may be less important than other mechanisms. Usually, there is no family history of similar seizures, although siblings with Panayiotopoulos syndrome or Panayiotopoulos syndrome and rolandic epilepsyRolandic epilepsy
In neurology and pediatrics, benign rolandic epilepsy or benign epilepsy with centrotemporal spikes is the most common epilepsy syndrome in childhood. Most children will outgrow the syndrome , hence the label benign...
or, less common, Panayiotopoulos syndrome and idiopathic childhood occipital epilepsy of Gastaut have been reported. There is a high prevalence of febrile seizure
Febrile seizure
A febrile seizure, also known as a fever fit or febrile convulsion, is a convulsion associated with a significant rise in body temperature...
s (about 17%).
SCN1A mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s have been reported in a child and in 2 siblings with relatively early onset of seizures, prolonged time over which many seizures have occurred, and strong association of seizures with febrile precipitants even after the age of 5 years. However, no such mutations were found in another couple of siblings and homozygous twin
Twin
A twin is one of two offspring produced in the same pregnancy. Twins can either be monozygotic , meaning that they develop from one zygote that splits and forms two embryos, or dizygotic because they develop from two separate eggs that are fertilized by two separate sperm.In contrast, a fetus...
s with typical Panayiotopoulos syndrome and no febrile seizure precipitants. These data indicate that SCN1A mutations when found contribute to a more severe clinical phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
of Panayiotopoulos syndrome.
Pathophysiology
In Panayiotopoulos syndrome there is a diffuse multifocal cortical hyperexcitability, which is age (maturation)-related. This diffuse epileptogenicity may be unequally distributed, predominating in one area, which is often posterior. Epileptic discharges in Panayiotopoulos syndrome, irrespective of their location at onset, activate emetic and autonomic centers prior to any other conventional neocortical seizure manifestations. An explanation for this is that children are susceptible to autonomic disorders as illustrated by the cyclic vomiting syndrome, which is a nonepileptic condition specific to childhood.Panayiotopoulos syndrome and all other benign childhood focal seizures, with rolandic epilepsy as their main representative, are probably linked due to a common, genetically-determined, mild, and reversible functional derangement of the brain cortical maturational process that Panayiotopoulos proposed as "benign childhood seizure susceptibility syndrome". The various EEG and seizure manifestations often follow an age- (maturation-) related localization. Panayiotopoulos syndrome is probably the early onset phenotype of the benign childhood seizure susceptibility syndrome.
During a recorded autonomic seizure, there was a small increase in blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
(+5/4 mm Hg, systolic/diastolic), pronounced increases in heart rate
Heart rate
Heart rate is the number of heartbeats per unit of time, typically expressed as beats per minute . Heart rate can vary as the body's need to absorb oxygen and excrete carbon dioxide changes, such as during exercise or sleep....
(+59 bpm) and plasma concentrations of norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
(+242 pg/mL), epinephrine (+175 pg/mL), and vasopressin
Vasopressin
Arginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's...
(+22.1 pg/mL); serum glucose was also elevated (206 mg/dL). The significant increase in plasma vasopressin may explain the emetic autonomic symptoms.
Misdiagnosis
The clinical features of Panayiotopoulos syndrome are frequently mistaken as nonepileptic conditions such as acute encephalitisEncephalitis
Encephalitis is an acute inflammation of the brain. Encephalitis with meningitis is known as meningoencephalitis. Symptoms include headache, fever, confusion, drowsiness, and fatigue...
, syncope
Syncope
In phonology, syncope is the loss of one or more sounds from the interior of a word; especially, the loss of an unstressed vowel. It is found bothin Synchronic analysis of languages and Diachronics .-Found synchronically:...
, migraine
Migraine
Migraine is a chronic neurological disorder characterized by moderate to severe headaches, and nausea...
, cyclic vomiting syndrome
Cyclic vomiting syndrome
Cyclic vomiting syndrome or cyclical vomiting syndrome is a condition whose symptoms are recurring attacks of intense nausea, vomiting and sometimes abdominal pain and/or headaches or migraines...
, motion sickness
Motion sickness
Motion sickness or kinetosis, also known as travel sickness, is a condition in which a disagreement exists between visually perceived movement and the vestibular system's sense of movement...
, sleep disorder
Sleep disorder
A sleep disorder, or somnipathy, is a medical disorder of the sleep patterns of a person or animal. Some sleep disorders are serious enough to interfere with normal physical, mental and emotional functioning...
, or gastroenteritis
Gastroenteritis
Gastroenteritis is marked by severe inflammation of the gastrointestinal tract involving both the stomach and small intestine resulting in acute diarrhea and vomiting. It can be transferred by contact with contaminated food and water...
. The consequence is avoidable misdiagnosis, high morbidity, and costly mismanagement.
Prognosis
Panayiotopoulos syndrome is remarkably benign in terms of its evolution. The risk of developing epilepsy in adult life is probably no more than of the general population. Most patients have one or 2-5 seizures. Only a third of patients may have more than 5 seizures, and these may be frequent, but outcome is again favorable. However, one fifth of patients may develop other types of infrequent, usually rolandic seizures during childhood and early teens. These are also age-related and remit before the age of 16 years. Atypical evolutions with absences and drop attacks are exceptional. Children with pre-existing neurobehavioral disorders tend to be pharmacoresistant and have frequent seizures though these also remit with age.Formal neuropsychological assessment of children with Panayiotopoulos syndrome showed that these children have normal IQ and they are not on any significant risk of developing cognitive and behavioural aberrations, which when they occur they are usually mild reversible. Prognosis of cognitive function is good even for patients with atypical evolutions.
However, though PS is benign in terms of its evolution, autonomic seizures are potentially life threatening in the rare context of cardiorespiratory arrest.
Management
Continuous prophylactic antiepileptic drug (AED) treatment may not be needed particularly for children with only 1-2 or brief seizures. This is probably best reserved for children whose seizures are unusually frequent, prolonged, distressing, or otherwise significantly interfering with the child’s life. There is no evidence of superiority of monotherapy with any particular common AED.Autonomic status epilepticus in the acute stage needs thorough evaluation for proper diagnosis and assessment of the neurologic/autonomic state of the child. “Rescue” benzodiazepine
Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
s are commonly used to terminate it. Aggressive treatment should be avoided because of the risk of iatrogenic
Iatrogenesis
Iatrogenesis, or an iatrogenic artifact is an inadvertent adverse effect or complication resulting from medical treatment or advice, including that of psychologists, therapists, pharmacists, nurses, physicians and dentists...
complications, including cardiovascular arrest. There is some anecdotal concern that intravenous lorazepam
Lorazepam
Lorazepam is a high-potency short-to-intermediate-acting 3-hydroxy benzodiazepine drug that has all five intrinsic benzodiazepine effects: anxiolytic, amnesic, sedative/hypnotic, anticonvulsant, antiemetic and muscle relaxant...
and/or diazepam
Diazepam
Diazepam , first marketed as Valium by Hoffmann-La Roche is a benzodiazepine drug. Diazepam is also marketed in Australia as Antenex. It is commonly used for treating anxiety, insomnia, seizures including status epilepticus, muscle spasms , restless legs syndrome, alcohol withdrawal,...
may precipitate cardiovascular arrest. Early parental treatment is more effective than late emergency treatment. Buccal midazolam
Midazolam
Midazolam is a short-acting drug in the benzodiazepine class developed by Hoffmann-La Roche in the 1970s. The drug is used for treatment of acute seizures, moderate to severe insomnia, and for inducing sedation and amnesia before medical procedures. It possesses profoundly potent anxiolytic,...
is probably the first choice medication for out of hospital termination of autonomic status epilepticus which should be administered as soon as the child shows evidence of onset of its habitual autonomic seizures.
Parental education about PS is the cornerstone of correct management. The traumatizing, sometimes long-lasting effect on parents is significant particularly because autonomic seizures may last for many hours compounded by physicians’ uncertainty regarding diagnosis, management, and prognosis.