Alternating Hemiplegia of Childhood: A Physicians’ Guide for Diagnosis

Alternating Hemiplegia of Childhood: A Physicians’ Guide for Diagnosis

JUNE 16, 2017
Sho Yano MD PhD and Kenneth Silver MD


Alternating hemiplegia of childhood (AHC) is a rare genetic disorder that involves both paroxysmal and chronic neurological symptoms, and its name comes from the recurrent attacks of hemiplegia. Attacks have been known to affect either side in the same patient at different times, or even during the same attack („alternating“).

Beyond that, AHC patients can have paroxysmal attacks involving a wide variety of other abnormalities of movement, including dystonia, quadriplegia, nystagmus, and gaze palsy, and autonomic symptoms. The paroxysmal symptoms resolve with sleep, but may recur after the child awakens.

A patient may have multiple types of episodes, as well as a progression of symptoms during a single attack; for example, from hemidystonia with eye jerking to hemiplegia to flaccid quadriparesis.

Attack frequency ranges from multiple daily episodes to one every few months, and attacks can be triggered by changes in temperature or lighting, exposures to water, foods, specific activities, and other environmental stressors. Although the hemiplegic attacks themselves are not epileptic, about half of patients with AHC will also develop epilepsy.

In addition to the paroxysms, patients with AHC develop chronic neurological symptoms over time, including developmental delay, impairments in areas of cognition, executive functioning, behavior problems, and movement abnormalities such as ataxia, choreoathetosis, dystonia, and persistent weakness.

Onset of symptoms in classical AHC occurs prior to 18 months of age, and the initial symptom is often a paroxysmal abnormality of eye movement, which can include unusual findings such as monocular nystagmus and is sometimes associated with respiratory abnormalities, with mean age at onset of 2 months. Hemiplegic and dystonic episodes follow with a mean age at onset of 6-7 months. The paroxysmal and chronic symptoms evolve over time and both may cause significant distress and impairment. Both epileptic seizures or paroxysmal attacks are potentially life-threatening, and can involve significant autonomic symptoms such as bradycardia, respiratory distress, or sudden unexpected death in epilepsy (SUDEP).

Clinical suspicion for AHC in children with unexplained paroxysmal abnormalities of movement is essential to making the diagnosis, because the usual evaluations such as brain MRI, EEG, EMG, CSF analysis, and metabolic screening are often normal or non-specific in patients with AHC.

80% of patients with AHC have denovo heterozygous mutations in the ATP1A3 gene, which encodes one isoform of the neuronal ATP sodium-potassium pump alpha subunit. AHC clinically overlaps with other ATP1A3-related disorders, such as rapid-onset dystonia-parkinsonism. There is growing recognition of atypical AHC presentations, such as infrequent and long-lasting (months) episodes of encephalopathy and weakness which can be mistaken for aseptic meningoencephalitis.

There are currently no FDA approved medications for AHC. Observational evidence suggests that flunarizine may reduce the duration, severity, and/or frequency of episodes. Benzodiazepines or other medications to induce sleep or treat dystonia are sometimes used as abortive medications during attacks.

Epilepsy should be suspected if new types of episodes arise and should be treated appropriately with anticonvulsants if present. Families of patients with AHC may be able to reduce triggers for paroxysmal attacks and to monitor during episodes for symptoms that may require hospitalization, such as quadriparesis, respiratory distress, severe dystonia, and prolonged seizures.

Sho Yano M.D., Ph.D.
University of Chicago
Comer Children’s Hospital

Kenneth Silver M.D.
University of Chicago
Shriners Children’s Hospital Chicago


For the article click HERE

6th Symposium ATP1A3 in Disease – Tokyo japan

From the Organising Committee of the 6th Symposium ATP1A3 in Disease:

Our special thanks to the Organising Committee of the 6th Symposium ATP1A3 in Disease, chaired by Dr Masayuki Sasaki, for making the 2017 annual meeting a great success. The Tokyo event was attended by over 107 people and included some excellent presentations with new research and unpublished data. Thanks very much for all contributions!

We are also very pleased to announce that the next Symposium on ATP1A3 in Disease will take place at the Northwestern University Medical Center, Chicago, Illinois USA on October 13th and 14th (Saturday to Sunday) 2018.

The Organising Committee includes Allison Brashear, MD (Wake Forest Medical Center), Al George, MD (Northwestern University Medical Center), Kevin Ess, MD, PhD (Vanderbilt University Medical Center), and the AHC Foundation.

Kind regards.
The ATP1A3 in Disease Symposia Standing Committee

Cure based on CRISPR systems

Alternating Hemiplegia of Childhood (AHC) is a rare neurological condition which is clinically
characterized by recurrent episodes of temporary paralysis, often affecting one side of the
body (hemiplegia). In addition to paralysis, affected individuals can have sudden attacks of
uncontrollable muscle activity as well as mild to severe cognitive problems, developmental
delays, physical disabilities and intellectual disabilities[1]

Extended research shows strong correlation between mutations in the ATP1A3 gene and the
symptoms of AHC [11], therefore the ATP1A3 mutations are presently considered as the main
cause of AHC. Certain researches showed that on rare instances some mutations in the
ATP1A2 gene are also involved in this condition [9] [10]

and therefore mutations in the ATP1A2 gene will most likely be included in relevant continuation research efforts.
The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR
Associated (Cas) system Type II is a relatively new genome engineering technology that was
first described in 2013 and enables multiple types of DNA editing at specific targeted

Since 2013 thousands of publications were written describing the work that was done to
improve the accuracy of this mechanism, as well as describing experimentation on animal
and human cells as well as animal lab experiments [2] [3]

In addition, certain institutes have
shown that CRISPR can be used to eradicate HIV from human immune cell lines [5] [6] [23]
some commercial companies have started using the CRISPR systems in order to research a
treatment for rare blood disorders and other diseases [7] [52]

Common rationale states that a genetic condition will be most effectively treated and
permanently cured by a solution which is implemented at the genetic level. The ultimate
goal is to use a CRISPR system in order to remove the ATP1A3 mutations and replace them
with „healthy“ DNA sequences or use another type of DNA manipulation that will produce
an equivalent result. The goal for this preliminary study is to conduct a gap analysis process
with respect to the CRISPR technology’s capabilities and determine which steps should be
taken in order to eventually achieve the aforementioned ultimate goal.


Grants bolster research on rare neurological disorder AHC

Kevin Ess, M.D., Ph.D., Gerald M. Fenichel Professor of Neurology, has received two grants from the Alternating Hemiplegia of Childhood Foundation (AHCF).

Kevin C. Ess, MD,PhD

Kevin Ess, M.D., Ph.D.
The grants will support efforts to understand cellular and molecular defects that contribute to AHC, a rare neurological disorder that causes repeated, sporadic attacks of hemiplegia — paralysis of part of the body. Patients with AHC often also suffer developmental delay, epilepsy and dystonia (abnormal muscle tone).

The hemiplegia attacks in AHC may cause mild weakness to complete paralysis on one or both sides of the body — sometimes alternating between sides — and they can vary in duration from minutes to hours to days. Patients are usually diagnosed before 18 months of age and may initially be misdiagnosed as having a seizure disorder instead of hemiplegia.

In up to 75 percent of patients, mutations in the gene ATP1A3 cause the disease. ATP1A3 encodes a protein component of the sodium/potassium ATPase — a molecular pump that moves sodium and potassium ions across the cell membrane and is responsible for establishing and maintaining the electrical gradients that are important for nerve and muscle excitability.

In a project that AHCF has continuously supported since 2012, Ess and close collaborator Alfred George, M.D., at Northwestern University, are studying human neurons generated from AHC patient-derived stem cells.

They are also using gene editing approaches to correct the ATP1A3 mutations in patient-derived cells. In addition, they are screening drugs and compounds for their ability to correct the defect in order to identify potential new treatments for AHC.

Ess also received AHCF funding for a second complementary project, in which his team is generating specific antibodies directed against the alpha3 and alpha2 subunits of the sodium/potassium ATPase. These antibodies will be highly useful tools for assessing levels of the specific subunits of the sodium/potassium ATPase.

They will be used not only in the human stem cell-based models, but also in mouse models of AHC that are being developed, Ess said.

“This should be an excellent investment that should continue to pay dividends far into the future,” Ess added.

Ess is the director of the Division of Pediatric Neurology and leads an AHC clinic at Monroe Carell Jr. Children’s Hospital at Vanderbilt.

Media Inquiries:
Leigh MacMillan, (615) 322-4747

Skilaboð til hlaupara í Reykjavíkurmaraþoninu


Allir sem hlaupa fyrir AHC samtökin geta fengið bol og buff merkt AHC samtökunum og Sunnu Valdísi.

Nú þegar eru skráðir 23 hlauparar en gaman væri ef fleiri bættust í hópinn.

Til þess að nálgast bolina og buffin er best að hafa samband við foreldra Sunnu Valdísar:

Sigga 8989097 eða Röggu 6974550 eða senda póst á


Við þökkum ykkur kærlega fyrir að hlaupa fyrir samtökin og Sunnu sætu 🙂

Dr. Kathryn J Swoboda hleypur í Reykjavíkurmaraþoninu

Þekktur taugalæknir og genafræðingur Kathryn J Swoboda hleypur fyrir Sunnu Valdísi og AHC samtökin í Reykjavíkurmaraþoninu þetta árið.

Kathryn hefur síðustu 20 ár verið einn helsti sérfræðingur um AHC og SMA og er einnig með rannsóknarstofu í Cambridge, MA þar sem hún vinnur að því að finna meðferðir við SMA og AHC.
Kathryn verður hér á landi í nokkra daga en gefur sér tíma til þess að skoða eina AHC sjúklinginn á Íslandi, Sunnu Valdísi Sigurðardóttir og einnig ætlar hún sér að hlaupa í Reykjavíkurmaraþoninu ásamt syni sínum og frænda.

Þegar Sunna Valdís lenti inn á spítala árið 2008 með óstöðvandi AHC köst þá var það ráðleggingar frá Dr. Swoboda sem björguðu lífi Sunnu Valdísar.

Sunna var búin að vera í hrikalegum köstum í 11 daga og gat ekki lengur borðað, gengið, var með ósjálfráðar hreyfingar og læknarnir á Íslandi höfðu engin ráð. Sunna var að fá yfir 50 köst á dag og hrakaði stöðugt.

Faðir Sunnu, Sigurður Hólmar fékk gsm símanúmer hjá Dr. Swoboda gegnum Bandarísku AHC samtökin.

Dr. Swoboda svaraði símanum þrátt fyrir að vera í sumarfríi og leiðbeindi svo íslensku taugalæknunum hvernig væri best að taka næstu skref. Sunna var svæfð og haldið sofandi í 4 daga. Þegar hún var vakin þá hélt hún áfram að fá köstin en svo fækkaði þeim og að lokum stoppuðu þau eftir nokkra daga. Sunna þurfi að vera í stífri enduhæfingu í 3 mánuði á eftir til þess að læra að, borða, ganga og hreyfa sig eðlilega aftur.

Það er nokkuð ljóst að án ráðlegginga Dr. Swoboda þá hefði Sunna Valdís ekki lifað þetta af….

Allar götur síðan hefur Dr Swoboda ráðlagt með umönnun Sunnu Valdísar.

Hérna er hægt að heita á Dr. Kathryn

Human Timebombs wins another award

„Human Timebombs“ has won the title for Best Global Impact Award for the 7th edition of Move Me Productions’ Festival.“

Congratulations Agusta Fanney, this is the 4th award the film receives. We could not be happier 🙂

#humantimebombs #raredisease #rareconnect

6th Symposium on ATP1A3 in Disease

6th Symposium on ATP1A3 in Disease will be held in September 21 and 22, 2017 in Tachikawa, Tokyo, Japan

The 1st Symposium on ATP1A3 in Disease was held in Brussels, Belgium in December 2012, when it was first discovered that alternating hemiplegia of childhood (AHC) was caused by ATP1A3 mutations. Since then the symposiums have been held in Europe and the US. This is the first time that the symposium will be held in Asia. We hope that doctors and researchers who are interested in this field and many family members will attend the symposium.

ATP1A3 encodes the Na+/K+-ATPase α3 subunit which is expressed mainly in the central nervous system. Na+/K+-ATPase is an essential transmembrane protein, which is ubiquitously expressed in all animal cell membranes. The Na+/K+-ATPase transports and exchanges 3Na+ and 2K+ through the plasma membrane using energy from an ATP. This pump function was discovered 60 years ago (1957), and it is said that 30% of cellular ATPs are used by Na+/K+-ATPase in living creatures.

Thirteen years ago (2004), the first human disease caused by ATP1A3 mutations was discovered. It was rapid-onset dystonia–parkinsonism (RDP), which mainly occurs in adulthood. Eight years later (2012), three independent research groups (Heinzen et al, Rosewich et al, and Ishii et al) reported that AHC was caused by ATP1A3 mutations. AHC mainly occurs in early childhood. Since then several rare conditions other than RDP or AHC have been demonstrated to be caused by ATP1A3 mutations. In this symposium, we would like to discuss the physiological functions of the Na+/K+-ATPase, the characteristics of ATP1A3-related diseases, and the possible new treatment methods for ATP1A3-related diseases.

Four AHC associations fund international AHC patient registry


AHC Vereniging Nederland, AHC UK support groupCure AHC and the AHC Association of Iceland have joined forces to fund the IAHCRC-CLOUD platform which will be operated by the International AHC Research Consortium in collaboration with patient driven AHC associations.
This project is headed by Rosaria Vavassori who is the IAHCRC Data Manager and will be crucial for new studies, trials and collecting of information for the international AHC community.

The IAHCRC-CLOUD platform will be developed by the IEMEST Institute

The IAHCRC International Consortium for the Research on AHC and other ATP1A3 related diseases was created officially on November 2014

The Consortium involves clinicians, geneticists and researchers working at University centers in Europe, USA and Australia; it works in close collaboration with health professionals and patients

IAHCRC-CLOUD Platform is an on-line platform that collects and hosts data from IAHCRC Centers and from external sources and shares them for the IAHCRC Studies and Projects. The registry is Accessible to Researchers, Clinicians and Patients

AHC samtökin óska eftir styrk

Fyrir sjaldgæfa sjúkdóma er nauðsynlegt að hafa nákvæma sjúklingaskrá sem rannsakendur og læknar geta dregið upplýsingar úr þegar verið er að vinna að rannsóknum.

AHC samtökin á Íslandi vilja styðja við alþjóðlega rannsóknarhópinn IAHCRC sem er búinn að undirbúa gerð sjúklingarskrár en vantar fjármagn til þess að klára verkefnið
Verkefnið þarf 20.000 Evrur eða um 2.3m isk og óskum við hér með eftir stuðningsaðila/aðilum sem væru tilbúnir að hjálpa til við að láta þetta mikilvæga verkefni verða að veruleika.
Þeir sem hafa áhuga hafi samband í síma 8989097 eða sendi email á