Studies on brain electrical signaling offer a fresh perspective on vertebrate evolution, provide additional evidence supporting Darwinian views of evolution, and may also lead to more effective treatment of epileptic seizures in infants. Studies at the University of Pennsylvania. One child never has another seizure. Twenty years later, the other child has a series of seizures and is diagnosed with epilepsy. A study being. Epilepsy research years after Darwin's theory of evolution. Pesquisas em epilepsia anos após a teoria da evolução de Darwin. Fulvio A. ScorzaI; Vera .
Evolves Epilepsy Research
Godlee in the National Hospital of London. Both Theodor Kocher — , a Swiss surgeon from Bern, Nobelist, and pioneer in epileptic surgery, and Harvey Cushing — , father of modern neurological surgery, in Baltimore dealt with posttraumatic epileptic disorders especially with patients displaying high endocranial pressure [ 85 , 86 ].
In , Horsley — excised an epileptogenic posttraumatic cortical scar at the National Hospital of London in a year-old man under general anesthesia and discussed his choice of anesthesia: At the beginning of the 20th century, Dandy — introduced hemispherectomy as a neurosurgical procedure in [ 90 ].
However it was not until the s than important advances were made in epileptic surgery. The notion of operating the epileptogenic focus was introduced by Gibbs and Lennox in [ 91 ]. The introduction of EEG into epilepsy surgery was important in the development of surgical techniques. Penfield along with Jasper and Theodore Brown Rasmussen — in the Neurologic Center of University of Montreal also contributed importantly to the evolution of the surgery of epilepsy [ 92 , 93 ]. Penfield applied the Foerster method for removing epileptogenic lesions on an epilepsy patient.
After founding the Montreal Neurological Institute MNI , in , in collaboration with Jasper, he invented the Montreal procedure for the surgical treatment of epilepsy. Then the surgeon proceeds in the removal of brain tissue in this location reducing the side effects of surgery [ 94 ]. Through his operations, Penfield was able to identify various brain centers and to create maps of the sensory and motor cortices of the brain. Research in MNI focused also on other areas of epileptology such as neurochemistry, oncology, and brain angiology.
Penfield perfected and established his surgical procedures as a treatment of choice in intractable epilepsy, especially of neocortical regions [ 94 — 96 ]. In , Penfield published with Jasper one of the greatest classics in neurology, Epilepsy and the Functional Anatomy of the Human Brain [ 93 ]. Bailey — , an American neuropathologist, neurosurgeon, and psychiatrist, known for his work on brain oncology, was the first to attempt temporal lobectomies for psychomotor seizures and the first to use electrocorticography for intraoperative localization [ 98 ].
One should also mention the method of hemispherectomy introduced by McKenzie — [ 99 ] and Krynauw in [ ]. Bailey and Gibbs in employed the EEG as a guide to perform temporal lobe surgery [ 98 ], whereas, in , Falconer, a neurosurgeon from New Zealand, in London, introduced the en bloc anterior temporal lobe resection and the term mesial temporal sclerosis [ ].
The work of Margerison and Corsellis led to the term of hippocampal sclerosis [ ], a pathological entity which was initially described almost 80 years earlier by Sommer in [ ].
Niemeyer, in , suggested a more selective procedure of resection of the mesiobasal limbic structure [ ], a technique which was later on abandoned. The next important step in the field of antiepileptic surgery was done by Tailarach and his team. Within this operating room teleradiography would take place and the use of parallel X-ray beams would avoid distortions of skull, vessels, ventricles, and the frame and grids used for guiding the placement of intracranial electrodes.
The first stereotactic surgery operating room was opened in Sainte-Anne in [ ]. Their method brought a revolution in the surgery of epilepsy, since it allowed investigative presurgical and therapeutic surgical phases to be completely dissociated. Tailarach and Bancaud employing their technique showed that lesional and irritative zones had a variable topographic relationship within the epileptogenic zone [ 14 ].
During the s, Bogen and Vogel reintroduced the procedure of callosotomy [ ] as a procedure for certain cases of pharmacoresistant epilepsy with severe atonic akinetic seizures.
In , White published a comprehensive review on the surgical procedure of hemispherectomy summarizing the results of published cases [ ] in the treatment of infantile-type hemiplegia and seizures.
At the beginning of the s, in the field of antiepileptic surgery, MTLE suggested selective amygdalohippocampectomy AHE with the trans-Sylvian approach, replacing the anterior temporal lobe resection [ ]. As far as therapies and the neurophysiology of epilepsy are concerned, much were already known during the second half of 19th century.
Treatment of epilepsy till that time mostly consisted of herbal and chemical substances. In , Sir Locock — discovered the anticonvulsant and sedative traits of potassium bromide and began treating his patients.
From that point, potassium bromide became a choice treatment for humans with epileptic seizures and nervous disorders until the discovery of phenobarbital [ ]. In , Hauptmann — , a German physician, introduced phenobarbital in the therapy of epilepsy, one of the first antiepileptic drugs [ ].
Phenobarbital was brought to market by the drug company Bayer using the brand Luminal. Hauptmann administered Luminal to his epilepsy patients as a tranquilizer and discovered that their epileptic attacks were susceptible to the drug. The introduction of animal models in the study of the anticonvulsant properties of various substances will contribute to the development of new antiepileptic drugs.
The next drug introduced in the therapy of epilepsy was phenytoin in Although phenytoin was already known from and was synthesized by Heinrich Biltz — , there was no interest for that drug since it did not have any sedative properties. Merritt — , an eminent academic neurologist, along with Putnam — , discovered, in , the anticonvulsant properties of phenytoin Dilantin and its effect on the control of epileptic seizures publishing their results in a series of papers [ — ].
Phenytoin became the first-line medication for the prevention of partial and tonic-clonic seizures and for acute cases of epilepsies or status epilepticus, giving an alternative therapeutic choice for patients not responding to bromides or barbiturates. In , a new antiepileptic drug was added in the quiver of antiepileptic therapy, trimethadione; it was reported by Richards and Everett to prevent pentylenetetrazol-induced seizures and to be effective especially in absence seizures [ ].
During the s, new drugs came up such as carbamazepine in [ ], primidone in , ethosuximide in by Vossen [ ], sodium valproate in by Meunier et al. Buchtal and Svensmark were the first ones in to measure the levels of the antiepileptic drugs in the blood [ ]. Although carbamazepine and valproate were available in Europe during the s, no other drug was licensed in the USA.
Jean Pierre — and Pierre Deniker — , French psychiatrists, used chlorpromazine in Centre Hospitalier Sainte Anne in Paris to treat patients with schizophrenia. However, research on neuroleptic drugs continued in Geigy labs; carbamazepine was synthesized by Schindler and Blattner ? Geigy AG, Basel, Switzerland, , in the course of development of another antidepressant drug imipramine [ ].
Initial animal screening showed that carbamazepine was effective against trigeminal neuralgia, which was confirmed by clinical trials [ ]. Antiepileptic effects were reported in and [ , ]. It was used as an anticonvulsant drug in the UK since and has been approved in the USA since The reason for the delay of approval in the USA was due to reports of aplastic anemia caused by the drug [ ].
In , valproate came up as a new promising antiepileptic drug. The anticonvulsant properties of valproate were reported by Pierre Eymard, who worked at Firma Berthier laboratories in Grenoble, and it was first released as antiepileptic drug in France in [ ] after the publication of preclinical studies by Garraz et al.
During , it received license to other European countries, but in the USA it was not licensed before In , Penry and Cereghino were employed in designing clinical trials for antiepileptic drugs AEDs. Harvey Kupferberg joined their team and together they developed a methodology for measuring the blood-levels of albutoin, an experimental drug which was proved to be ineffective in epilepsy. The first edition of Antiepileptic Drugs came forth as a result of their research efforts in [ ]. Carbamazepine was the first drug to be licensed by the FDA based on the results of clinical trials.
Pippenger developed methods for measuring blood-levels of AEDs [ ]. Other antiepileptic drugs introduced during the s were clobazam 1,5-benzodiazepine , clonazepam 1,4-benzodiazepine , and piracetam.
The last decade newer antiepileptic drugs such as vigabatrin , lamotrigine , oxcarbazepine , gabapentin , felbamate , topiramate , tiagabine , zonisamide in Japan and in the USA , levetiracetam , stiripentol , pregabalin , rufinamide , lacosamide , eslicarbazepine , and perampanel were used.
FDA ended clinical use of felbamate in due to its association with complications. The newer generation antiepileptic drugs including vigabatrin, felbamate, gabapentin, lamotrigine, tiagabine, topiramate, levetiracetam, oxcarbazepine, zonisamide, pregabalin, rufinamide, and lacosamide have improved tolerability and safety compared to their older counterparts.
Stiripentol, pregabalin, rufinamide, lacosamide, eslicarbazepine, and perampanel are licensed for adjunctive use only. The research in antiepileptic drugs is an active field and many drugs are currently under development in clinical trials including eslicarbazepine acetate, brivaracetam, and retigabine. Two large-scale, phase III clinical trials have been conducted for retigabine.
In both studies, AEs leading to discontinuation included dizziness, somnolence, headache, and fatigue [ — ]. Ketogenic diet was used for the first time in the treatment of epilepsy in by the French physicians Guelpa and Marie. It was introduced as a diet full of fats and low in proteins and carbohydrates and managed to treat 20 children and adults with epilepsy reporting decrease in the number of seizures [ ]. However, fasting and other diets were employed for the treatment of epilepsy since the Hippocratic era [ ].
In , Hugh Conklin, an osteopathic physician from Michigan, applied this diet to epileptic patients with encouraging results. Conklin believed that epilepsy was due to toxins that damage the brain and so he obliged his patients to a strict diet.
Several papers have been published about the usefulness of ketogenic diet and the indications that will lead to the beginning of such a treatment [ , ]. Epilepsy affects approximately 3 percent of the general population and is a complex disease. At least 11 genes have now been described for human epilepsy and over 50 more genes have been identified in animal models of epilepsy.
The complex gene to gene interactions and gene-environment interactions may account for epilepsy susceptibility and antiepileptic drug response. Darwin's thoughts on evolution are relevant to understand these gene interactions, contributing to current development of new treatments and prevention of chronic diseases, such as epilepsy.
On February 12, , we commemorated the th anniversary of Charles Darwin's birth Figure. Charles Robert Darwin was born on 12 February in Shrewsbury, Shropshire, into a wealthy and well-connected family. He was the fifth of six children of wealthy society doctor and financier Robert Darwin, and Susannah Darwin. His maternal grandfather was china manufacturer Josiah Wedgwood, while his paternal grandfather was Erasmus Darwin, one of the leading intellectuals of 18 th century England. Darwin himself initially planned to follow a medical career.
He studied at Edinburgh University, but later switched to divinity at Cambridge. In , he joined a five-year scientific expedition on the survey ship HMS Beagle. He came up with his fascinating ideas in the Galapagos Islands, miles west of South America 1,2. On his return to England in , Darwin tried to solve the riddles of these observations and the puzzle of how species evolve.
He described "I can remember the very spot in the road, whilst in my carriage, when to my joy the solution occurred to me; and this was long after I had come to down. The solution, as I believe, is that the modified offspring of all dominant and increasing forms tend to become adapted to many and highly diversified places in the economy of nature.
The animals and plants best suited to their environment are more likely to survive and reproduce, passing on the characteristics which helped them survive to their offspring. Gradually, the species changes over time. Darwin worked on his theory for 20 years and, in , he published " On the origin of species ". From the strong principle of inheritance, any selected variety will tend to propagate its new and modified form. Quite interestingly, Darwin had very little to say about the brain in the first edition of the Origin 4.
A search through the digitized version of his work http: Thus, ictal symptoms and signs may signify the site of seizure spread rather than origin.
Both normal cerebral connectivity and neuronal pathways developed in the process of epileptogenesis likely participate in seizure spread. Munari and Bancaud [ 22 ] described ictal fear, epigastric and olfactory sensations, and oroalimentary automatisms consequent to seizure spread from the orbital frontal cortex to the amygdala and insula.
Suspect this situation in any patient with: Three approaches to the mesial temporal region have been described: Our surgeons have accessed the mesial temporal structures via the middle temporal gyrus Steven DA, personal communication. However, often a full temporal lobectomy has been performed Parrent A, personal communication.
Surgical approach and technique have not measurably changed over the years. That a substantial left temporal lobectomy will significantly impair verbal memory has become increasingly realized over the past decades creating a distinction between left and right temporal epilepsy in terms of surgical candidature [ 24 , 25 ].
Concern about verbal memory and other verbal functions has raised considerably our threshold for left temporal lobectomy over the past several years.
Epilepsy Research and Treatment. Abstract Although the advent of MRI impacted significantly our presurgical investigation, ictal semiology with interictal and ictal EEG has clearly retained its roles in localizing epileptogenesis.
Electroencephalography EEG Combined with ictal semiology, ictal and interictal EEG were the principal tools before the mids to localize epileptogenesis in virtually all patients whose intractable focal epilepsies required resective surgery for alleviation.
View at Google Scholar M. View at Google Scholar W. Gibbs, Atlas of Electroencephalography , vol. View at Google Scholar R. Frontal Lobe Seizures and Epilepsies , P. View at Google Scholar D. View at Google Scholar F.
Epilepsy Research and Treatment
The UK Epilepsy Society is years old. Now a leader in research and patient support, the history of this once 'home for such epileptic. The purpose of this study was to present the evolution of views on epilepsy as a disease and symptom during the 19th and the 20th century. Epilepsy Research and Treatment Slowly Evolving Trends in Temporal Lobe Epilepsy Management at London Health Sciences Centre.