Evolution of Dravet syndrome over time

  • Dravet syndrome is a rare type of life-lasting epilepsy. The first signs of this syndrome are seizures during the first year of life in a normally developing child.
  • The seizures vary but usually persist throughout the patient’s lifetime, but also this syndrome affects psycho-motor development and cognitive functions.

1/ Clinical course

  • Dravet syndrome has an age-dependent evolution of seizures. Three stages may be identified:
  • The onset phase (children under one year of age)
  • The worsening phase (children between about one and five years of age)
  • The stabilisation phase (children over about five years of age)

A/ THE ONSET PHASE

Children under one year of age

  • The first epileptic event generally occurs “out of the blue” between age of 4 and 8 months in a child who is developing normally and has no history to suggest a problem. Most often the first seizure is induced by a mild fever (37-38°C) from an illness or following a vaccination. Usually this is a
    clonicMore or less rapid jerky movements, repeated at more or less regular intervals.
    seizure, either initially
    generalisedSeizure that affect all the body
    or just one side of the body (
    hemiclonicClonic seizures that only affect half of the body
    ). If it is one side, it may remain on that side or spread to both sides and become generalised. The first seizure is typically prolonged seizure (>15 minutes) that sometimes turns into a
    status epilepticusSeizures lasting for more than 30 minutes
    ( >30 minutes).
  • Over the next weeks or months the child will have other seizures,
    febrileWith fever
    or
    afebrileWithout fever
    , despite the use of anticonvulsive medications. At this point, the electroencephalogram (EEG) and other neuroimaging investigations (
    CT scan Seizures lasting for more than 30 minutes
    ,
    MRIMagnetic Resonnance Imaging
    ) are nearly always normal.

B/ The worsening phase

Children between about one and five years of age

  • During this period, the seizure frequency increases. Seizures can occur with or without fever, and often include episodes of
    status epilepticusSeizures lasting for more than 30 minutes
    .
  • Other types of seizures appear:
    myoclonic seizuresSudden, very brief movements, sometimes repeated, similar to "jumping" (the physical reaction to being startled).
    ,
    atypical absencesAbsences difficult to recognise because they start and end gradually
    and
    focal seizuresSeizures involving only a limited area of the brain.
    . Some environmental factors may trigger them: excessive or intermittent flashes of light or special patterns or designs such as regular geometric patterns, lines, or dots, physical effort, or even excitement.
  • During this phase seizures are often extremely frequent, intense and prolonged resulting in multiple hospitalisations.

c/ The stabilisation phase

Children over about five years of age

  • From the middle of childhood and into adolescence, seizures generally improve, with a reduction and sometimes disappearance of
    focal seizuresSeizures involving only a limited area of the brain.
    ,
    atypical absencesAbsences difficult to recognise because they start and end gradually
    and
    myoclonic seizuresSudden, very brief movements, sometimes repeated, similar to "jumping" (the physical reaction to being startled).
    .
    febrileWith fever
    convulsive seizures Seizures including more or less violent motor phenomena (hypertonia, convulsions…).
    usually persist, although the number of fevers is less.
  • The number and length of convulsive seizures decreases but convulsive seizures rarely stop completely. These seizures often cluster together, especially at the beginning or at the end of the night.
  • In the majority of patients
    status epilepticusSeizures lasting for more than 30 minutes
    is considerably less frequent.

2/ Psycho-motor & cognitive development

  • Dravet syndrome has a characteristic developmental evolution. Developmental delay and
    intellectual disabilityDefined by the World Health Organisation as a significantly reduced ability to understand new or complex information and to learn and apply new skills (impaired intelligence). This results in a reduced ability to cope independently (impaired social functioning), and begins before adulthood, with a lasting effect on development.
    are nearly always present.
  • Just as in the clinical course of seizures, three stages may be identified although the ages may vary:
  • The onset phase (children under one year of age)
  • The worsening phase (children between about one and five years of age)
  • The stabilisation phase (childhood and adolescence)

A/ THE ONSET PHASE

Children under one year of age

Psychomotor and cognitive developments are usually normal throughout the first year of life.

B/ The worsening phase

Children between about one and five years of age

  • Between the first and second year of age a general slowdown in development is often observed. Intellectual and behavioural disorders appear. Their severity may vary from one child to another. Speech and language are the first to be impacted, but most other areas of development are gradually affected.
  • The child is often moody,
    hyperkinetic Said of a child who can’t stay still, always moving.
    , contrary, stubborn, and obstinate. Communication problems make social interaction even more difficult. Sleep disorders are common.
  • Many of the children have problems with coordination including uncoordinated gait (
    ataxia Motor disorder occurring without paralysis, characterised by a defect in movement coordination, with movement becoming uncoordinated, poorly adapted to its goal, particularly in walking, which can lead to balance difficulty and falling.
    ) and problems with fine motor skills (hand and finger coordination).

C/ The stabilisation phase

  • When reaching this phase, psychomotor and cognitive disorders tend to stabilise. Development may continue slowly or restarts if there has been a period of regression.
  • Permanent
    intellectual disabilityDefined by the World Health Organisation as a significantly reduced ability to understand new or complex information and to learn and apply new skills (impaired intelligence). This results in a reduced ability to cope independently (impaired social functioning), and begins before adulthood, with a lasting effect on development.
    varies from moderate to severe, depending on the evolution during the previous years.
  • Communication often remains difficult and
    autistic traitsDifferent manifestations of the child's behaviour evoke autism but there is no real autism: difficulty in communication through language or look (evasive look), restricted interest in others (children and adults), stereotyped, repetitive play and activities.
    may be observed. In general the speech abilities match the child’s overall intellectual level, but comprehension of language remains better than the ability to produce speech.
  • An occasional person has aggressive behaviour or even
    psychosisRefers to an abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality". Psychosis is the term given to the more severe forms of psychiatric disorder, during which hallucinations and/or delusions, violence and impaired insight may occur.
    .

3/ Long-term outcome

Because Dravet syndrome has only been recognised since 1991, the long-term evolution and life expectancy are not well-known.

However, based on the clinical experience of a number of expert physicians, early appropriate management of Dravet syndrome seems to result in a better outcome.

A/ Mortality rate

  • The mortality rate for patients with all types of epilepsy is higher than in the general population.
  • Dravet syndrome-related mortality is estimated to be 10 - 15%, with most deaths in children or young adults. The causes of death vary and include infections, epileptic seizures,
    status epilepticusSeizures lasting for more than 30 minutes
    , and accidents such as falls or drowning but sometimes may be unexplained (medically defined as
    SUDEPAccording to the World Health Organization SUDEP is defined, as the sudden, unexpected, unexplained, witnessed or unwitnessed, nontraumatic, and nondrowning death in patients with epilepsy, with or without evidence of a seizure.
    ).
  • The majority of people with Dravet syndrome live well into adulthood.

B/ in adulthood

  • In adulthood nearly all patients with Dravet Syndrome present a handicap that can express itself through slow movement, poor and slow language sometimes without making sentences with even dysarthria that worsen after the age of 40.
  • Although the seizures are less frequent than in childhood, adult Dravet patients still have seizures.
    Intellectual disabilityDefined by the World Health Organisation as a significantly reduced ability to understand new or complex information and to learn and apply new skills (impaired intelligence). This results in a reduced ability to cope independently (impaired social functioning), and begins before adulthood, with a lasting effect on development.
    and coordination problems preclude independent living.
  • Motor impairment also impact the Dravet adult population such as
    ataxia Motor disorder occurring without paralysis, characterised by a defect in movement coordination, with movement becoming uncoordinated, poorly adapted to its goal, particularly in walking, which can lead to balance difficulty and falling.
    , tremor myoclonus, clumsiness. Most are dependent on others for assistance with many activities of daily living.
  • Many have problems walking with flat feet, kyphoscoliosis and a special crouched gait. Some require a wheel chair for mobility.