What are infantile spasms?
Infantile spasms is a rare epileptic disorder in small children. It is considered an epileptic encephalopathy appearing during the first year of life with 4 months being the average age of manifestation. In some cases though, infantile spasms have a later onset until the second year of life(late onset infantile spasms).
Infantile spasms often have a subtle, not impressive onset and justifiably parents may not pay attention, ignoring the impact this has on their children’s general health.
Usually when people think of an epileptic episode, what they have in mind is a dramatic picture of a person that loses consciousness, collapses on the floor with violent movements, hyper salivation and eye starring. This is a very disturbing image that easily leads to the conclusion that this person needs medical attention.
An infant with infantile spasms can only exhibit a mild forward head flexion or a subtle eye movement that may appear insignificant to the untrained eye. Still these subtle episodes constitute a much more significant epileptic disorder than a generalized tonic clonic seizure.
The brain of the child with infantile spasms is completely functionally disorganized resulting to loss of precious time in a very critical period for its development and consequently the child’s psychomotor development.
Infantile spasms is a rare disorder and a pediatrician is expected to be faced with one or two cases during his practice.
Their frequency, subtle clinical picture and possible similarity to other more frequent disorders of infancy like startle reflex or colic can mislead even an experienced pediatrician resulting to misdiagnosis or delayed diagnosis.
The role of the pediatrician
Knowledge and alertness can result in prompt recognition and referral for evaluation and therapy.
Timely recognition is of critical importance because early initiation of appropriate treatment can result in a better neurocognitive outcome of a disorder with a generally bad prognosis.
What do we call West Syndrome?
The term West syndrome is often used synonymously with infantile spasms. However officially infantile spasms refer to a type of seizures which are common but not exclusive to West Syndrome.
West Syndrome is an age-related electro-clinical syndrome resulting from multiple and diverse causes. It is characterized by the triad of infantile spasms as the presenting clinical symptom, a distinct electroencephalographic pattern called hypsarrhythmia and possible concurrent neurodevelopmental stagnation.
What do we call infantile spasms?
The term infantile spasms usually refers to the specific epileptic syndrome “infantile spasms syndrome” or “ West Syndrome” or to a specific type of seizures preferably called epileptic spasms. Epileptic Spasms are synonymous to Salaam attacks.
The official seizure classification puts them under the category “unknown”,
because of our inability to understand their exact pathophysiology.
Infantile Spasms-Clinical Manifestation
As we mentioned before very often these episodes are initially subtle and seem insignificant until they are fully blown.
The full clinical picture manifests in a few weeks with spasms typically occurring in one or multiple daily clusters with every cluster having multiple attacks.
These attacks are usually sudden flexion of the neck and lower limbs towards the abdomen sometimes resembling a mild “startle reflex”. They are very brief lasting 1-2 seconds.
This tonic contraction is followed by relaxation and after a few seconds the same attack happens again.
During an episode this sequence is repeated periodically in the majority of children many times. The intensity and frequency of the spasms in each cluster often increase progressively to a peak, and then decline until they stop.
More rarely the spasms are extensor. In some children only 2-3 paroxysms happen in a cluster. There are also cases where infantile spasms occur singly rather than in clusters.
It is usual for a child to cry or laugh at the end of a cluster.
Infantile spasms happen mainly upon arousal and alertness but stimuli like feeding can trigger an episode.
Two thirds of the children usually have prior (pre-morbid) mild or severe developmental delay while one third have history of normal development.
With the appearance of infantile spasms more psychomotor development stagnation is observed.
What are the causes of infantile spasms?
The causes of infantile spasms are multiple and diverse. The most common causes are pre-, peri -, or postnatal ischemic brain insults.
Other common causes are congenital central nervous system malformations, intracranial hemorrhage, trauma, congenital infections, neurocutaneous and genetic syndromes (e.g Down syndrome). Less common causes are inborn errors of metabolism (like pyridoxine disorders).
A very common cause of infantile spasms is tuberous sclerosis. Half of these children will exhibit epileptic spasms and prompt diagnosis is important because of their favorable response to Vigabatrin
Etiological classification of infantile spasms.
West Syndrome is classified as symptomatic, cryptogenic and idiopathic.
What are Symptomatic infantile spasms?
Symptomatic epileptic syndrome is called a syndrome where the epileptic episodes are a result of one or more underlying brain disorders.
Symptomatic infantile spasms are by far the most common consisting about 80% of total. The percentage varies depending on the diagnostic competence of each medical center.
What are cryptogenic infantile spasms?
Cryptogenic epileptic spasms are called those where the patients are strongly suspected of being symptomatic but investigations have failed to identify an etiological diagnosis.
What are idiopathic infantile spasms?
The term idiopathic infantile spasms describe cases without any identifiable cause and no other neurological signs or symptoms.
These children have normal pre-morbid psychomotor development, possibly a positive family history of epilepsy and good prognosis with regard to development.
Infantile spasms and genetic mutations.
Rarely children with infantile spasms have been found to carry mutations in specific genes like the ARX which is located at the short arm of X chromosome. (INFANTILE SPASM SYNDROME, X–LINKED 1) (ISSX1).
Nowadays with the fast evolution in genetics more genes have been associated with infantile spasms (ARX, CDKL5, FOXG, GRIN1, GRIN 2A, MAGI, MEF2C, SLC5A22, SPTANI, STXBP1, 15q11q13) revealing the cause of many cases of cryptogenic infantile spasms and making a future genetic therapy seem possible.
How are infantile spasms diagnosed?
The diagnosis is achieved through clinical observation of the episodes and confirmed with an EEG study which in the majority of cases interictally shows the characteristic EEG pattern of infantile spasms, hypsarrhythmia .
Sometimes a routine EEG especially at the initial stages can show subtle non characteristic findings and create the need for a prolonged study in order to identify and record the episodes. The EEG findings during an episode are characteristic.
What is hypsarrhythmia?
Hypsarrhythmia is the interictal EEG pattern observed in 2/3 of patients with infantile spasms. A child with hypsarrhythmia almost always will have infantile spasms.
Hypsarrhythmia is a chaotic pattern, characterized by a disorganized mixture of high amplitude, arrhythmic, asynchronous, slow and sharp waves with multi-focal spikes without recognizable normal electrical rhythms.
What is the significance of the EEG?
Apart from its diagnostic value, the EEG helps with the evaluation of the therapeutic result. The therapeutic aim for infantile spasms is both the elimination of the clinical episodes as well as the hypsarrhythmia on the EEG.
Diagnostic procedure-Etiological investigation
When the infantile spasms are verified one must seek what is causing them. As we said before there are various causes.
In some cases we know the preferred pharmacological treatment.
Neuroimaging can identify the majority of etiological causes while complementary tests like genetic and metabolic tests will reveal rarer disorders without obvious structural brain abnormalities.
Investigation should aim to exclude tuberous sclerosis because this diagnosis guides the pharmacological treatment choice.
What is the prognosis of infantile spasms?
West syndrome is a catastrophic epileptic encephalopathy.
The prognosis of these children is essentially determined by the underlying etiology. Even when the spasms are successfully treated, the majority of the children will end up with severe permanent neurological problems like different pharmacoresistant epileptic episodes and neurodevelopmental disorders like autism.
Cryptogenic and especially idiopathic infantile spasms have a better prognosis compared to symptomatic.
Why is it important to diagnose and treat infantile spasms?
Recent studies (UKISS) have shown that early diagnosis leading to early initiation of therapy and faster response to treatment can positively influence the neurodevelopmental prognosis especially for children with cryptogenic and idiopathic infantile seizures.
What do we consider as treatment success?
We consider successful treatment in West Syndrome the 100% resolution of clinical episodes as well as the resolution of hypsarrhythmia on EEG.
Which is the appropriate treatment for infantile spasms?
The most appropriate treatment for infantile spasms is early treatment initiation.
There are three different pharmacological treatment choices. The 2 of them are hormonal therapies. First treatment is oral steroids and the second is intramuscular adrenocorticotropic hormone (ACTH). Third choice is Vigabatrin, which is a more conventional anticonvulsant treatment with proven efficacy for the treatment of infantile spasms.
These are the 3 most effective treatment choices, with 2 of them (ACTH and Vigabatrin) being supported by more evidence. Oral steroid treatment is still under debate concerning efficacy, dosage, preparation and dosage scheme.
Alternative Treatments-Ketogenic Diet
Based on the studies of Kossoff et al from Johns Hopkins (which is a reference center for ketogenic diet), ketogenic diet can play an important role in the treatment of infantile spasms when other treatments fail. Evidence show that it can be more efficient compared to more conventional treatments.
An alternative treatment is pyridoxine. In some countries, especially Japan, the therapeutic protocol for infantile spasms has large doses of B6 (pyridoxine) as a first line choice before ACTH.
Alternative Therapies-Epilepsy Surgery
In the cases where conservative measures fail and in selected patients, epilepsy surgery constitutes an important choice.
In symptomatic pharmacoresistant spasms with localized brain lesions, epilepsy surgery can play a significant therapeutic role.
Ideal patients for epilepsy surgery are children with pharmacoresistant epileptic spasms and single unilateral focal lesion on MRI or focal area that shows hypometabolism on FDG PET that does not affect the motor area or the visual cortex.
PROMPT RECOGNITION OF INFANTILE SPASMS IS OF EXTREME IMPORTANCE.
TIME IS OF THE ESSENCE BECAUSE EARLY DIAGNOSIS AND APPROPRIATE THERAPY CAN MODIFY (ALTER) THE HISTORY OF A PREDETERMINED CATASTROPHIC COURSE FOR A CHILD WITH INFANTILE SPASMS.
Ioannou Ioannis, MD