NEWS - YEAR 2020
3 AUGUST 2020
With great sadness, we read the announcement of the passing of Professor Paul Casaer on the website of the International Child Neurology Association ICNA
With great sadness, we read the announcement of the passing of Professor Paul Casaer former ICNA President & Emeritus full Professor in Paediatrics-Paediatric Neurology, KU Leuven, on 30 July 2020. link
Born on 22nd September 1940 in Belgium, Professor Casaer made many major contributions to the field of paediatric neurology. But the AHC patient and scientific community will always remember him with admiration and gratitude for the fundamental role that he played in assessing the efficacy of Flunarizine as chronic treatment for this rare and complex neurological disease. Thanks to the positive results of his double-blinded international trial with Flunarizine published in 1987, the quality of life of so many AHC patients has been improving since then all over the world. link
Prof. Casaer also contributed to the ENRAH Project (2005 -2009) for the creation of the European Registry for AHC and to the international collaboration that led to the discovery of the AHC-causing mutations in the ATP1A3 gene (2012).
27 June 2020
ANOTHER GREAT STUDY ABOUT BEHAVIORAL PROBLEMS IN AHC PUBLISHED BY THE DUKE GROUP
In the article (Wallace K, Uchitel J, Prange L, Jasien J, Bonner M, D'Alli R, Maslow G, Mikati MA. Characterization of Severe and Extreme Behavioral Problems in Patients with Alternating Hemiplegia of Childhood. Paediatr Neurol. 2020 Jun 27. doi: 10.1016/j.pediatrneurol.2020.06.012) published by the group of the AHC Clinic at the Duke University Medical Center, directed by Professor Mohamad Mikati, they analyzed 39 consecutive AHC patients for occurrence of behavioral problems.
- Six (15%) patients had extreme problems defined as those present in major risk of injury to themselves or to others
- Ten (26%) had severe problems which presented minor risk of injury to themselves or to others
- Five (13%) had moderate problems defined as requiring intervention but presenting no risks of injury
- Two (5%) had mild problems defined as not requiring interventions
- Sixteen (41%) had no behavior problems
Triggers noted in many patients
- low frustration tolerance
- limits set by others
- sleep disruption
- Some medications
Reversible psychotic symptoms occurred in 2 of the 39 patients
- In one, the trigger was trihexyphenidyl
- In the above patient infection was a trigger on another occasion
- In another patient, the trigger was the medication sertraline.
- Diagnosis and therapy of coexisting neuropsychiatric diagnoses like anxiety, depression or attention deficit disorder
- Involvement of a multidisciplinary team including mental-health professionals neurology and developmental Pediatrics
- Medications targeting the patient’s specific problem and coexisting neuropsychiatric diagnosis and that often alpha-adrenergic agonists and SSRIs.
- Forty one percent of AHC patients often experience severe/extreme behavioral problems
- On rare occasions, AHC patient may have medication-triggered psychotic symptoms.
- These correlate with the known AHC brain pathophysiology.
- Awareness of these behavioral problems should allow anticipatory guidance and better management of such problems when they occur in some AHC patients
You can read the article at this link
10 April 2020
FOUR SEQUENTIAL ARTICLES ON AHC PUBLISHED BY THE DUKE GROUP
The group of the AHC Clinic at the Duke University Medical Center directed by Professor Mohamad Mikati, has recently published four sequential articles about Alternating Hemiplegia of Childhood.
These are their comments and recommendations about each article.
- In the article by Ghusayni et al. (Ghusayni R, Richardson JP, Uchitel J, Abdelnour E, McLean M, Prange L, Abrahamsen T, Song A, Petrella JR, Mikati MA. Magnetic resonance imaging volumetric analysis in patients with Alternating hemiplegia of childhood: A pilot study. Eur J Paediatr Neurol. 2020 Feb 13:S1090-3798(20)30032-5.) they used the technique of Quantitative MRI to determine the volume of different brain regions of AHC patients as compared to normal controls. First they determined that the use of this technique whether automated using the special program called FreeSurfer or done by manual segmentation of different brain regions was highly reproducible with high correlation between automated and manual segmentation and between two consecutive manual segmentations. Then they found that there was a negative correlation between cerebellar volume and age of 14 patients studied suggesting that cerebellar volume may decrease with age in AHC patients. Given that this is a cross sectional study (each patient’s MRI was evaluated once) there is a need to perform prospective studies in which serial MRIs are done on the same patient to definitively determine volume changes with time.
This study showed that the techniques used can be used perform such studies in AHC patients. Depending on the results of such studies the above technique could potentially be useful as an outcome measure, biomarker, to follow progress of AHC patients during long-term therapeutic trials. link
- In the article of Tran et al. (Tran L, Richards J, McDonald M, McConkie-Rosell A, Stong N, Jasien J, Shashi V, Mikati MA. Epileptic encephalopathy with features of rapid-onset dystonia Parkinsonism and alternating hemiplegia of childhood: a novel combination phenotype associated with ATP1A3 mutation. Epileptic Disord. 2020 Feb 1;22(1):103-109.) a four-year, nine-month-old boy is reported who presented with the following manifestations.
1) Frequent and recurrent episodes of focal and generalized tonic seizures and of convulsive status epilepticus since the age of four months of age with concurrent developmental delay that started with the onset of the seizures.
2) Recurrent attacks of unilateral and bilateral hemiplegia between the ages of 7 months and 2.5 years.
3) Regression at the age of 21 months, after a febrile illness with status epilepticus, with development of continuous severe dystonia and bradykinesia with superimposed intermittent painful dystonic spasms.
The etiology was determined to be a novel and de novo p.V589F ATP1A3 mutation.
This article showed that this ATP1A3 mutation caused a combination phenotype that features of each of epileptic encephalopathy, alternating hemiplegia of childhood, and rapid-onset dystonia Parkinsonism. Thus, physicians and caretakers taking care of patients with epileptic encephalopathy should be on the lookout for symptoms of AHC and regression with dystonia as combination phenotypes can occur. link
- In the article of Uchitel et al. (Uchitel J, Abdelnour E, Boggs A, Prange L, Pratt M, Bonner M, Jasien J, Dawson G, Abrahamsen T, Mikati MA. Social impairments in alternating hemiplegia of childhood. Dev Med Child Neurol. 2020 Feb 7.) they studied 34 AHC patients of social responsiveness an autism. They found that 27 of the 34 AHC patients had impaired social responsiveness as indicated by a high Social Responsiveness Scale, Second Edition (SRS-2) scores as compared to the scores of normally developing individuals. In these AHC patients, all categories of social responsiveness were impaired. These included social cognition, social communication, social awareness, social motivation, restricted interests, and repetitive behavior. The presence of epilepsy increased the chance of impaired social responsiveness. Of these 27 patients at the time of the completion of the study, 9 had been referred for formal evaluations of autism and all those nine had been diagnosed to have autism spectrum disorder.
This study highlighted the importance of screening AHC patients, as early as possible, for autism spectrum disorder symptoms and of referring them for formal evaluation for autism as this will allow them be appropriately managed and will allow them to have more resources for their management. link
- In the editorial written by Fernandes and Mikati (Fernandes C, Mikati MA. The expanding spectrum of ATP1A3 related disease. Eur J Paediatr Neurol. 2019 May;23(3):345-346.) the authors review expanding spectrum of ATP1A3 related disorders and provide a table that shows the distinct and overlapping symptoms of these diseases. These include in Alternating Hemiplegia of Childhood (AHC), Rapid Onset Dystonia-Parkinsonism (RDP), Relapsing encephalopathy with cerebellar ataxia (RECA), Childhood schizophrenia, autism, epileptic encephalopathy, Cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing loss (CAPOS), and childhood rapid onset ataxia (CROA). The symptoms associated with these syndromes are presented in a succinct table for quick reference and comparison. There are, in addition, many reported patients with intermediate and combination phenotypes.
The editorial then argues that based on the above observations, the presence of multiple symptoms associated with ATP1A3 mutations even if the patients do not fit a specific syndrome should raise the suspicion of ATP1A3 related disease. In the absence of any other clear etiology, this should lead to gene sequencing of such patient to rule out an ATP1A3 mutation. link
30 March 2020
RECOMMENDATIONS on COVID-19 and EPILEPSY CARE
Recommendations on COVID-19 and Epilepsy Care developed by EpiCARE, the European Reference Network for Rare and Complex Epilepsies.
They are available in many languages at this link
20 February 2020
"EPILEPSY AND CANNABIDIOL: A GUIDE TO TREATMENT"
16 January 2020
"A NEW ARTICLE FROM THE GASLINI GROUP ABOUT WHITE MATTER AND CEREBELLAR INVOLVEMENT IN ALTERNATING HEMIPLEGIA OF CHILDHOOD"
This is an overview of the article from the authors at the Scientific Institute and University Hospital G. Gaslini, Genoa, Italy.
What was the objective of the study?
The study objective was to determine whether brain volumetric and white matter microstructural changes are present and correlate with gravity and type of neurological impairment in subjects with Alternating Hemiplegia of Childhood (AHC).
How many patients were enrolled?
12 AHC subjects (mean age 23 years) and 24 healthy controls with the same age were enrolled.
What methods and techniques were used?
We used advanced MRI techniques to evaluate white matter volume and microstructure abnormalities in AHC subjects. Neuro-radiological data have been correlated with motor impairment and clinical disability scales results.
What were the results?
AHC subjects showed prevalent white matter involvement, with reduced volume in several cerebral and cerebellar regions associated with widespread microstructural changes reflecting secondary myelin injury rather than axonal loss. Conversely, no specific pattern of grey matter atrophy emerged. Lower cerebellar volumes, correlating with severity of neurological manifestations, seems related to disrupted developmental rather than neurodegenerative processes.
The article is available at this link.