Taking the gloves off. Historically, epilepsy is called the falling sickness because of episodes when patients suddenly crash to the ground and lose their posture. These seizures are called atonic or astatic seizures and are often the most troubling events for patients. During these events, patients may seriously hurt themselves. From the epileptological point of view, there is a long debate regarding the nature of these events. Are they purely due to loss of posture or are they associated with a brief myoclonic seizure? Lennox quotes Pierce Clark who states bluntly that describing an astatic seizure without a preceding jerk is due to “faulty clinical observation”. This is when Lennox takes the gloves off.
Category Archives: 2012
Traveling with Lennox – myoclonic jerks, West Syndrome and the 34th meridian
Where is West Syndrome? Earlier this week while browsing through the contents of Lennox’s book, I wondered where his description of West Syndrome was hidden. Lennox is very careful in reviewing the historical data on epilepsy, but for some reason, he did not mention the report by William James West, who described a particular type of epilepsy in his own son that would later be named after him. Then, when I had almost forgotten that I was on the lookout for West Syndrome, I stumbled upon it in the chapter on myoclonic seizures. Continue reading
Traveling with Lennox – the petit mal triad
Lights on and lights out. Staring spells, petits mals, pyknolepsy and absence seizures. The brief spells that occur in patients with epilepsy have riddled neurologists for centuries. This became clear to me when Zaid Afawi and myself saw an epilepsy family in the West Bank on Sunday. When are staring spells epileptic and what kind of seizures are they? For me, this was a good opportunity to read Lennox’s thoughts on this. Eventually, after a long day under the Middle Eastern sun, I fell asleep over the chapter on absence status. Continue reading
Traveling with Lennox – on my way to the Old New Land
On the road. For this week, the Channelopathist will be a travel blog. I am on my way to Israel where we will be busy recruiting and phenotyping epilepsy families for the EuroEPINOMICS project for the next seven days. This trip abroad gives me the opportunity to do something that I have been thinking about for quite some time: reading “Epilepsy and Related Disorders” by William G. Lennox, one of the pioneers of epilepsy genetics. I will try to put some thoughts on Lennox into words this week while spending my time down here in Israel. Continue reading
Finding the difference: de novo mutations in schizophrenia
The story continues. This week, I am trying to catch up with a number of recent papers in the field of neurogenetics. A recent publication in Nature Genetics highlights the role of de novo mutations identified through exome sequencing in schizophrenia. The authors also look at control data and compare their findings with the growing body of data available for autism research. And while many aspects regarding de novo mutations become more clear with every study published, the real difference is sometimes difficult to grasp. Continue reading
Genome meets Connectome: gene networks and brain microstructure
Genetic imaging. There are two major fields in epilepsy research – functional imaging and genetics. Both fields live parallel lives and hardly ever interact. When they do, the interaction is usually short-lived and full of disappointments, as nothing has really ever worked. However, a grant application due today has led me to a recent publication in the Journal of Neuroscience, which combines imaging and GWAS. And believe it or not, the ion channels are back. Continue reading
De novo mutations in severe intellectual disability
Diagnostic exome sequencing. Severe intellectual disability (ID) is unexplained in the vast majority of patients and is thought to be genetic. The genetics of intellectual disability has traditionally focused on the X chromosome, where more than 100 possibly causative genes for ID are located. But other, autosomal genes are also found in large number of cases. A recent study in the New England Journal of Medicine now reports on trio exome sequencing in patients with unexplained severe intellectual disability. The authors identify causative de novo events in a large proportion of patients. Interestingly, more than half of their patients had epilepsy. Continue reading
Close encounters of the third kind – rare genetic variants in families
A new beast. Rare genetic variants probably account for a significant fraction of the genetic liability to many common and rare disorders. Rare variants occupy the liability space between monogenic variants and common genetic variants. Their existence has often been postulated, and genetic investigations looking at copy number variants have elucidated some examples of rare variants. These rare variants appear to carry particular properties that are quite unexpected including the way that these variants run in families. Now, in a recent paper in the European Journal of Human Genetics, we have developed a model of the way rare variants behave in families. And there is a lot of misbehaving. Continue reading
Gamification of life science – The CAGI challenge
Everybody wins. The scientific publication process is not ideal to find the best bioinformatics methodology for a given problem. Most predictions are not performed blind as our data sets are so small that separating them in to several disjoints sets for training and testing purposes is not possible or sensible. The structural biology community has started to tackle the problems by establishing a competition called Critical Assessment of protein Structure Prediction (CASP). For example, the solution of the 3D structure of a protein is announced but the data withheld for a couple of months to give computational groups time to submit a prediction which is then evaluated by an independent team. A concluding conferences crowns the best prediction groups. In recent years, systems biology and sequence interpretation produce sufficient data to make similar challenges possible. Continue reading
Face to face – atypical face shape and CNVs in epilepsy
Face scan. A large high-tech camera scans your face in 3D and – using more than 30,000 data points – extracts information from your face that you were not aware of including details of your genetic make-up. What sounds like dystopic Gattaca-like science fiction at first is actually an interesting novel technique to learn more about epilepsy-related microdeletions. It seems that some of their effects might be hidden in subtle facial features that might help understand how these genetic variants contribute to disease. Continue reading
