ahc

Alternating Hemiplegia of Childhood

Introduction

Alternating Hemiplegia of Childhood (AHC) is a neurological disorder which triggers recurrent episodes of weakness or paralysis on either side of the body as well as on both sides in all those who are affected by it.

AHC is a complex disorder which in addition to the above with few or many of the additional symptoms mentioned below.

Essentially all AHC patients also have manifestations of dystonia (abnormal muscle tone), nystagmus (rapid movement of eyes), and many also have other abnormal limb movements, epilepsy, postural and balance problems, cognitive delays, behavioural issues, and delayed developmental milestones, difficulty in fine and gross motor skills, speech and language impairment.

At molecular level, ATP1A3 gene encoding the alpha subunit of Na+/K+ -ATPase pump is implicated in AHC.

AHC is an ultra-rare disease (affects 1 in 1,000,000 population) which is currently incurable. Little or no treatment is available for AHC.

Definitions

Alternating hemiplegia: This means the paralysis or weakness on one side of the body and shifts to another side on the onset of next episode. Though it is not strictly alternating every time, it mostly alternates.

Alternating Hemiplegia Childhood: This means that the onset of AHC is generally in between birth to 18 months old. The hemiplegic/quadriplegic attacks can vary greatly in duration and generally cease completely with sleep. It is to be noted that there are adults living with AHC, who started to have symptoms in their early childhood.

Cause and Diagnosis

Although the cause of AHC is unknown, a number of different triggers have been identified in association with episodes. Stress, infection and certain environmental triggers commonly trigger episodes. Common environmental triggers include exposure to bright lights, flashing lights, loud sounds, changes in temperature, excitement or other strong emotions, or bath or pool water. However, attacks might occur without any trigger as well.

Clinical diagnosis includes understanding the pattern of episodes of the child correlating specific symptoms. Most of the times, it is commonly misdiagnosed as epilepsy. DNA sequencing as a confirmatory test can specifically look for mutation of ATP1A3. In India very few cases have been reported or diagnosed so far.

What is ATP1A3 gene?

ATP1A3 gene (present in the DNA) encodes alpha-subunit protein of the Na+/K+ -ATPase pump protein complex. This integral membrane protein, in part, is responsible for establishing and maintaining electrochemical gradients of sodium and potassium ions across the plasma membrane of neuronal cells.

In I971 researchers Simon Virret and John C. Steeve first reported the occurrence of AHC. The cause of the disease remained unknown till 2012 when it was found that mutations of the ATP1A3 gene are the cause in the majority of cases. Genes provide instruction for creating protein that play key roles in the various functions of the body, like development of brain cells, nerves, growth of limbs transport of Sodium, potassium or calcium ions and their electrical charging to activate various functions including higher functions of brain and other systems. Mutation of a gene if it occurs, the protein production becomes faulty or absent or inefficient and the resultant protein is unable to carry out its function as needed in the cell. Depending on the function of particular proteins, this can affect many organs of the body including the brain.

In AHC the ATP1Aa3 gene is mutated. In most cases this mutation occurs at the time of egg or sperm production for that child only and consequently in most of the case no other member of the family is affected.

This type of de-novo mutation is the usual cause of AHC, and it is more common than the inherited type. ATP1A3 gene is responsible for production of ATPase enzyme as explained above, which conducts the sodium, potassium ions transport, across nerve cells and fibres helping brain activity. If a mutation occurs, it causes a wide variety of symptoms pertaining to the functions of brain and the heart rhythm. In some AHC cases ATP1A3 mutation is not found and in these cases other genes such as CACNA1, SLC2A1, ATP1A2 need to be checked for possible mutations.

Developmental delay/cognitive challenges like Autism

Development delays including delays rolling over, sitting, standing, walking and in the development social skills are seen in AHC. They also have difficulty in speech and understanding. Some kids exhibit symptoms like repeating the same sentence/question instead of reacting or answering the question. They are often impulsive and hyperactive. However unlike children with autism they do are usually engaging and even manipulative of their care takers and are able, given the right conditions, to follow instructions.

Epilepsy/Seizures

Seizures or epilepsy would mostly be the first diagnosis of kids with AHC as about 50% of them actually have epilepsy. However almost all of them, even the ones who do not have epilepsy, are initially misdiagnosed for epilepsy alone. The epilepsy could be in the form of generalized or one sided stiffening (tonic) and or rhythmic shaking (clonic) activity. It also can take the form of staring and unresponsive seizures (complex partial seizures).

Behavioural problems

AHC is a genetic congenital neurological disease with symptoms stating as early as at birth and as a rule before the age of 18 months. The cardinal symptoms are episodes of one sided paralysis that last minutes, hours or days that often subside with sleep as well as episodes of total body paralysis and of stiffening of different parts of the body or all the body that also last minutes, hours or days. Development is delayed. Behavioral issues like impulsivity, short temper, difficulty in communication, poor concentration and learning problems often occur.

Movement problems like cerebral palsy

Kids with AHC have movement problems like involuntary movement of limbs and body. Typically, a dance like movement with hands clenched parallel to chest is seen while walking.

Some of them are unable to walk or have involuntary movements in walking. They also exhibit exaggerated reflexes when excited. Since the muscle tone is less and their motor control is affected, they have difficulties in chewing and swallowing food. Difficulty in bowel control and hence difficult to toilet train AHC patients during the early years can also occur.

Management and Treatment

As on now, there is not specific treatment for AHC. However antiepileptic drugs are used in reducing the frequency of the movement disorder episodes. Yet such drugs are not effective in most cases.

Sleep can be very helpful in recovering from episodes. Hence the Neurologist might prescribe such medications to induce sleep such as chloral hydrate or benzodiazepines such as Valium or Midazolam.

Management of AHC includes keeping the child’s nutrition level in good state in order to improve the development and improving the quality of life. Physiotherapy, occupationaltherapy, speech-therapy, special education for learning disabilities can be given based on the child’s development.

Future mainly depends on research and clinical trials. As of now many countries in the world actively participate in research of AHC.

Indian institutions such as NIMHANS - Bengaluru, AIIMS - New Delhi have Paediatric Neurologists who are familiar of AHC and its diagnosis and management. Duke AHC clinic of Duke University, North Carolina, USA specializes in AHC.