Observe Alternating Hemiplegia of Childhood (OBSERV-AHC) Study

Study Overview
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Brief Summary
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Alternating Hemiplegia of Childhood (AHC) is a rare and serious disease that is in need of effective, and hopefully even curative, therapies. Afflicted patients suffer from severe paralyzing crises, often excruciatingly painful muscle spasms, severe often life threatening epileptic seizures, and frequently severe developmental and psychiatric/psychological disabilities. Based on the repeated input from family organizations and from professionals, as expressed at the London 2016 ATP1A3 in Disease meeting, there are urgent clinical research needs for AHC that are essential to better understand the disease, evaluate its treatment options and plan for future controlled clinical trials. The goal of the study is to evaluate different parameters involved in the evolution of the AHC. The investigating team's hypothesis is that the evolution is variable so it aims to evaluate the factors which could contribute to the progression of the disease.

Official Title
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Observe Alternating Hemiplegia of Childhood (OBSERV-AHC) Prospective Observational Natural History and Therapy Study

Conditions
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Alternating Hemiplegia

Intervention / Treatment
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* Other: Review of past medical history, clinical exam, and electroencephalogram, polysomnography and urine samples of melatonin and pupillometry.
* Other: The patients' parents have to complete the VINELAND II adaptive behavior scales scoring, The Sleep Disturbance Scale for Children (SDSC) and Horne & Ostberg Circadian Typology Questionnaire


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Patients who fit the Aicardi Alternating Hemiplegia of Childhood clinical criteria of any age. The Aicardi Criteria are six : Paroxysmal hemiplegia episodes. Bilateral hemiplegia or quadriplegia episodes. Other paroxysmal manifestations, such as abnormal eye movements, nystagmus, strabismus, ataxia, dystonia, choreoathetosis, tonic spells, or autonomic disturbances. Evidence of permanent neurological dysfunction, which can manifest as cognitive impairment, developmental delay, and/or persistent motor deficits such as spastic diplegia/quadriplegia, hypotonia, ataxia, choreoathetosis, or dystonia. Sleep relieves symptoms, although attacks may resume soon after awakening. First signs of dysfunction occur prior to the age of 18 months. Exclusion Criteria: Patients who do not have a mutation of the ATP1A3 gene and having only some of the above criteria Patients and / or their parents / legal guardian having provided their opposition to the study. Incapacity of patient / parent or other referent adult to participate in the prospective phase of observation of different paroxysmal events of the disease and in the scoring of the Vineland II adaptive behavior scales. Diagnosis of another disease, which could explain the presence of symptoms mentioned in the criteria of Aicardi.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with Alternating Hemiplegia of Childhood (AHC)<br>Patients who fit the Aicardi Alternating Hemiplegia of Childhood clinical criteria of any age. The Aicardi Criteria are six (Heinzen et al 2015). (1) Paroxysmal hemiplegia episodes. (2) Bilateral hemiplegia or quadriplegia episodes. (3) Other paroxysmal manifestations, such as abnormal eye movements, nystagmus, strabismus, ataxia, dystonia, choreoathetosis, tonic spells, or autonomic disturbances. (4) Evidence of permanent neurological dysfunction, which can manifest as cognitive impairment, developmental delay, and/or persistent motor deficits such as spastic diplegia/quadriplegia, hypotonia, ataxia, choreoathetosis, or dystonia. (5) Sleep relieves symptoms, although attacks may resume soon after awakening. (6) First signs of dysfunction occur prior to the age of 18 months. Patients having some but not all the above criteria and have the mutation in ATP1A3 gene can be included. | Other: Review of past medical history, clinical exam, and electroencephalogram, polysomnography and urine samples of melatonin and pupillometry.<br>* Review of past medical history; review of paroxysmal events; identification of presence of seizures & epilepsy & epilepsy classification; characterization of the non-paroxysmal features; degree of paroxysmal, non-paroxysmal disability indices; Vineland II adaptive behavior scales scoring; behavioral evaluation; presence of a genetic mutation; pharmacological treatments already used; AHC paroxysmal events assessement during the time of study; patient calendar for the follow up of events, for the follow up of epileptic seizures; whether, or not, there was occurrence of a serious or potentially life-threatening event (status epilepticus, apnea requiring intervention, or death) during time of study; growth and somatic complaints; further information concerning family history & comorbidities; past instrumental & biochemical investigations (ECG, cardiac ultrasound results if done as part of patient's follow-up); electroencephalogram; polysomnography; urine samples of melatonin ; pupillometry<br>Other: The patients' parents have to complete the VINELAND II adaptive behavior scales scoring, The Sleep Disturbance Scale for Children (SDSC) and Horne & Ostberg Circadian Typology Questionnaire<br>* Sleep Disturbance Scale for Children ; Horne & Ostberg Circadian Typology Questionnaire<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| final index compared to the initial index of non-paroxysmal disability | The aim is to study the modification of the final index compared to the initial index of non-paroxysmal disability in order to evaluate the parameters that influence its evolution. The non-paroxysmal disability index is calculated from different variables : ability to walk independently, presence of a behavioral disorder, presence and degree of communication disorders, abnormality of global motor skills, abnormality of fine motor skills, movements disorders, intellectual deficiency. The study also aims to evaluate the sleep architecture in AHC | 1 year: Inclusion Visit up to 1 year visit |