Historical documents on epilepsy: From antiquity through the 20th century.

Historical documents dating back almost 4500years have alluded to the condition of epilepsy, describing signs and symptoms that are well-known today. Epilepsy was thought to be a mystical disorder by almost all Ancient cultures, including the Babylonians, Egyptians, Greeks, Indians, Iranians and Chinese. Hippocrates was the first to de-mystify the condition of epilepsy, providing a more scientific approach to the condition. As the signs and symptoms of epilepsy occurred without an obvious cause, the idea stood that it was a mystical phenomenon of divine punishment. This portrayal persisted through the early centuries of the common era, including the Middle Ages. It was not until the 16th and 17th century that Paracelsus, le Pois and Sylvius started to investigate internal causes for epilepsy. By the beginning of the 18th century, the general opinion on epilepsy was that it was an idiopathic disease residing in the brain and other inner organs. This resulted in Tissot writing the first modern book on epilepsy. Research continued in the 19th century with Jackson describing different types of seizures and many researchers showing interest in electroencephalography (EEG). The 20th century saw more detailed research being done on epilepsy and EEG, in addition to the establishment of many epilepsy-associated medical societies. The goal of this historical documentation is to provide an overview of the most important milestones in the history of epilepsy.

Cerebral Palsy: A Lifelong Challenge Asks for Early Intervention.

One of the oldest and probably well-known examples of cerebral palsy is the mummy of the Pharaoh Siptah about 1196-1190 B.C., and a letter from Hippocrates (460-390 B.C.). Cerebral palsy (CP) is one of the most common congenital or acquired neurological impairments in paediatric patients, and refers to a group of children with motor disability and related functional defects. The visible core of CP is characterized by abnormal coordination of movements and/or muscle tone which manifest very early in the development. Resulting from pre- or perinatal brain damage CP is not a progressive condition per se. However, without systematic medical and physiotherapeutic support the dystonia leads to muscle contractions and to deterioration of the handicap. Here we review the three general spastic manifestations of CP hemiplegia, diplegia and tetraplegia, describe the diagnostic procedures and delineate a time schedule for an early intervention.

Highights in the history of epilepsy: the last 200 years.

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. A thorough study of texts, medical books, and reports along with a review of the available literature in PubMed was undertaken. The 19th century is marked by the works of the French medical school and of John Hughlings Jackson who set the research on epilepsy on a solid scientific basis. During the 20th century, the invention of EEG, the advance in neurosurgery, the discovery of antiepileptic drugs, and the delineation of underlying pathophysiological mechanisms, were the most significant advances in the field of research in epilepsy. Among the most prestigious physicians connected with epilepsy one can pinpoint the work of Henry Gastaut, Wilder Penfield, and Herbert Jasper. The most recent advances in the field of epilepsy include the development of advanced imaging techniques, the development of microsurgery, and the research on the connection between genetic factors and epileptic seizures.

Prognostic factors for subsequent epilepsy in children with febrile seizures.

OBJECTIVE: Epilepsy following febrile seizures (FS) has been estimated between 2% and 7%. It concerns a prospective study in a large sample of children with a long-term follow-up. The aim of this study is to identify the prognostic factors that can lead children with FS to epilepsy. METHODS: Children with a first episode of FS were included. We gathered information about prenatal and perinatal history, family history of FS and epilepsy in first- and second degree relatives, age at the time of the initial FS, dates of FS recurrences, focality, duration of the FS and recurrent episodes within the same febrile illness, height and duration of fever prior to the seizure, cause of the fever, and frequency of febrile illnesses. Patients were seen every 4-6 months and also at each recurrence. KEY FINDINGS: A group of 560 children with a first FS met all entry criteria. Epilepsy was recorded at 5.4%. Statistical analysis was performed between children with epilepsy and those with no afebrile seizure. We analyzed FS recurrences in accordance with the occurrence of epilepsy. From the third FS recurrence and beyond, only focality continued to have prognostic value. SIGNIFICANCE: Main prognostic factors for the development of epilepsy after FS are: (1) complex FS that increased the risk for epilepsy 3.6 times, (2) age at onset of FS beyond the third year of life that raised the risk 3.8 times, (3) positive family history of epilepsy 7.3 times, and (4) multiple episodes of FS about 10 times. Focality at the first and the second FS recurrence increased the risk of epilepsy about 9.7 and 11.7 times, respectively. Focality was the only factor that continued to be significant in further FS recurrences. A prognostic profile of each child with FS would be very useful for the follow-up of these children.

Febrile seizures: recent developments and unanswered questions.

BACKGROUND: Febrile seizures (FS) are typically observed in infants and children affecting 2-5 % of the pediatric population and are the commonest seizures in childhood. OBJECTIVES: The present review summarizes epidemiology, etiology, clinical picture, and diagnostic procedures as well as the therapeutic options and the different courses this disorder may take. METHOD: An extensive review of literature is performed, while views and aspects towards the pathogenesis of FS are stated. Risk factors for multiple recurrences of FS and for subsequent epilepsy are analyzed. Questions regarding the treatment and follow-up of children with FS are answered. RESULTS: Whereas the frequency of epilepsy following simple FS is estimated to be 1.0-2.2 % of patients, and thus does not differ from the risk of normal population, complicated FS are associated with an increased risk of subsequent epilepsy in 4.1-6.0 %. Febrile status epilepticus with focal symptoms may result in approximately 5 % of cases in complex partial epilepsy. Furthermore, multiple recurrences increase the risk for generalized epilepsy (>4 %). The immediate management of FS, intermittent prophylaxis, and the effectiveness of the treatment in combination with antipyretics are presented in detail. CONCLUSION: FS can cause a great anxiety and even panic to parents and to the whole family. Parents should be educated about the benign condition and the good prognosis. Although much information has been gained, much remains to be learned.

Helicobacter pylori infection has no impact on manometric and pH-metric findings in adolescents and young adults with gastroesophageal reflux and antral gastritis: eradication results to no significant clinical improvement.

The relationship between Helicobacter pylori (Hp) gastritis and gastroesophageal reflux disease (GERD) remains controversial. The aim was to investigate the association between Hp infection and gastroesophageal reflux (GER) and the impact of Hp eradication on esophageal acid exposure and motility in adolescents and young adults with Hp gastritis and GERD. Sixty-four patients with symptoms suggestive for GERD, of which 40 Hp-positive (group A) and 24 Hp-negative (group B), underwent endoscopy-biopsy, esophageal manometry and 24-hour pH-metry. All group A patients received eradication treatment and were re-evaluated six months later again with 24-hour pH-metry, esophageal manometry, endoscopy-biopsy and clinical assessment. At inclusion, there were no significant differences between the two groups regarding sex, age, grade of endoscopic esophagitis, manometric and pH-metry findings. All Hp-positive patients had an antral predominant gastritis. Eradication of Hp was successful in all patients, and gastritis and esophagitis were healed in all patients. The mean lower esophageal sphincter pressure (LESP) increased significantly from 11.25 mmHg before to 11.71 mmHg after eradication (P<0.05). A significant decrease in reflux index was observed (mean RI 6.02% before versus 4.96% after eradication (P<0.05). However clinical symptoms of GER improved not significantly after 6 months follow up. Conclusively, in children and young adults with GER symptoms and GERD, the presence or absence of Hp has no impact on manometric and pH-metric findings. Eradication of Hp infection results in increase in LESP with a consequent decrease in esophageal acid exposure but not significant clinical improvement.

Hallmarks in the history of cerebral palsy: from antiquity to mid-20th century.

Cerebral palsy (CP) is a term that has been applied over the years to a group of children with motor disability and related service requirements. The first conceptions of cerebral palsy and our knowledge about aetiology and pathogeny allow us to assume that cerebral palsy existed in the Ancient World. Although there is lack of detailed medical descriptions from before the 19th century, mentions to cerebral palsy can be found in representational art, literary sources and paleopathology; however, because of the poor medical documentation, the diagnosis of cerebral palsy must remain a more or less well-justified supposition. In the Ancient World, the first medical description of cerebral palsy was made by Hippocrates in his work "Corpus Hippocraticum". Concrete examples and definitions of cerebral palsy, however, did not emerge until the early 19th century with observations by William John Little; thus, Little was the first personality to intensely engage cerebral palsy. Towards the end of the 19th century, two more personalities emerged, adding to the historical hallmarks of cerebral palsy: William Osler and Sigmund Freud. The significant developments that have followed since then are all due to the contributions of these three personalities in the field of cerebral palsy.

Hallmarks in the history of enteral and parenteral nutrition: from antiquity to the 20th century.

Parenteral nutrition (PN) and enteral nutrition (EN) have a very long history, emerging in the ancient world and developing throughout the common epoch. This history dates back as far as 3500 bc to the ancient Egyptians, Indians, and Chinese. Their medical practices were the first reports of enteral feeding therapy, provided via rectum with enemas of wine, milk, whey, wheat, and barley. Hippocrates and Plato, in ancient Greece, were the first personalities to emphasize the importance of diet on health. In the following centuries, Erasistratus and Herophilus described the first notion of the circulatory system, and Oribasius and Celsus described the role of nutrition and disease. There is a great historical gap between the times of Galen (2nd century), who elaborated on the circulatory system; Ibn Zuhr (12th century), who constructed the first model of PN; and Capivacceus (16th century), who placed the first tube for EN. The 17th-19th centuries showed major developments in modern nutrition elements. Steps toward artificial nutrition began in 1628 with the detailed description of blood circulation by William Harvey; however, most of the advances in enteral and parenteral feeding techniques, solutions, and formulas took place in the 20th century. Over the last decade of the 20th century, research focused on metabolic control, multitude formulas, timing and the combination of EN and PN for intensive care patients.

Neurocutaneous melanosis: report of three cases and up-to-date review.

Neurocutaneous melanosis is a rare noninherited embryonic neuroectodermal dysplasia, which is observed sporadically and never affects the entire integument. The hallmark of neurocutaneous melanosis in the neonatal period is the presence of a large bilateral hairy dark nevus with satellite nevi over the trunk and neck. The diagnosis should be considered in neonates with large pigmented nevi and in those with more than 3 hairy dark nevi regardless of their size. Neonates with neurocutaneous melanosis are at risk of developing neurological problems. The most common neurological complications are hydrocephalus, seizures, cranial nerve dysfunction, and signs of spinal cord and root involvement. The authors report 3 cases of histologically confirmed neurocutaneous melanosis and describe the course of neurological symptoms and clinical findings including cognitive tests and neuroimaging. The case reports are complemented by an up-to date review on this clinical entity.

Amphotericin B formulations variably enhance antifungal activity of human neutrophils and monocytes against Fusarium solani: comparison with Aspergillus fumigatus.

OBJECTIVES: Lipid formulations of amphotericin B (AMBF) are widely used in the treatment of life-threatening infections caused by Aspergillus fumigatus and Fusarium solani. We aimed to compare the immunomodulatory effects of four AMBF, deoxycholate (DAMB), liposomal (LAMB), lipid complex (ABLC) and colloidal dispersion (ABCD), on the oxidative antifungal activities of human neutrophils (PMNs) and monocytes (MNCs) against hyphae of A. fumigatus and F. solani. METHODS: Human PMNs and MNCs were pre-incubated with 1 or 5 mg/L DAMB and 5 or 25 mg/L for each of LAMB, ABLC and ABCD. Hyphal damage was then assessed by XTT assay, and O2- production was assessed by cytochrome c assay. RESULTS: All agents resulted in increased hyphal damage induced by phagocytes against both A. fumigatus and F. solani (P < 0.05). The high concentrations of AMBF elicited higher phagocyte-induced hyphal damage of both fungi than the low concentrations. There was, however, no consistent superiority of any of the AMBF or substantial effector cell:target ratio-dependent differences in the degree of hyphal damage enhancement. By comparison, O2- produced by PMNs or MNCs upon hyphal challenge was not generally affected by any of the AMBF. F. solani hyphae were significantly more resistant to H2O2 than A. fumigatus. CONCLUSIONS: These findings suggest that AMBF have enhancing effects of variable degree on phagocyte-induced hyphal damage of A. fumigatus and F. solani. Other fungicidal mechanisms, perhaps non-oxidative, are more likely to mediate these immunomodulatory effects of AMBF on host defence against the two medically important filamentous fungi.

Which factors determine febrile seizure recurrence? A prospective study.

PURPOSE: Many factors have been studied as potential predictors of recurrent febrile seizures (FS), however the available data in literature are inconsistent. The aim of the present paper is to determine which factors are responsible for the first and for multiple recurrences of FS, in a large sample of children with a long-term follow up. METHODS: Two hundred and sixty children were followed after their first FS. The inclusion criteria were: a history of a first febrile seizure; no personal history of afebrile seizures; no previous anticonvulsant medication and age between three months and six years. The median time of follow up was 4.3 years. We had a contact with the families of the children every 4-6 months and also in every recurrence. RESULTS: Very significant prognostic markers for the first FS recurrence were low age at onset, recurrence within the same illness, frequent febrile episodes and maternal preponderance. Powerful prognostic factors that may predispose children who already have one recurrence to a second or more are low age at onset and especially positive family history of FS. Additionally, low temperature prior to the initial seizure is a powerful predictor for three or more recurrences. CONCLUSIONS: Prognostic factors for FS recurrence are a useful tool for the clinician. It is obvious that as many powerful predictors a child has, the greater will be the risk for FS recurrence.

Increased prevalence of silent celiac disease among Greek epileptic children.

Celiac disease is an immune-mediated enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. Many reports mention the association between epilepsy and celiac disease and the occasional presence of occipital corticosubcortical calcifications. We investigated 255 children with idiopathic epilepsy. Evaluation included use of routine, easily obtainable studies. Patients were screened for immunoglobulin A (IgA), immunoglobulin G (IgG) antigliadin antibodies and immunoglobulin A antitissue transglutaminase antibodies. Moreover, presence of IgA antiendomysial and antireticulin antibodies was screened. Patients with positive IgA antigliadin antibodies underwent a small intestinal biopsy. Controls consisted of 280 healthy children. Intestinal histopathologic changes, positive IgA antigliadin antibodies or IgG antigliadin antibodies, antireticulin antibodies, and antitissue transglutaminase IgA antibodies were found in five epileptic children but not in control subjects (P = 0.0241). Intracranial calcifications were not found in epileptic children with celiac disease. The findings indicate that prevalence of silent celiac disease is increased among children with idiopathic epilepsy; the type of epilepsy does not appear to play a role. Serum antitissue transglutaminase IgA antibodies could be a good marker for celiac disease screening. Occipital corticosubcortical calcifications are rarer in children with celiac disease and epilepsy.

Effectiveness of intermittent diazepam prophylaxis in febrile seizures: long-term prospective controlled study.

The efficacy of intermittent rectal diazepam prophylaxis is assessed in the prevention of febrile seizures. In a prospective randomized cohort trial, 139 children (77 girls, 62 boys) who experienced a first febrile seizure were allocated to two groups: group A, which received intermittent diazepam (n = 68), and group B, which received no prophylaxis (n = 71). All children had a 3-year follow-up. The inclusion criteria were no personal history of afebrile seizures, normal neurodevelopment, no previous anticonvulsant therapy, and age between 6 months and 3 years. Each group was stratified to low, intermediate, and high risk according to the available clinical data. The 36-month recurrence rates in the no-prophylaxis group were 83% in high-risk patients, 55% in intermediate-risk patients, and 46% in low-risk patients. In the prophylaxis group, the recurrence rates were reduced in all risk groups: 38%, 35%, and 33%, respectively. Intermittent diazepam prophylaxis reduces the recurrence rate mainly in high-risk children provided that sufficient doses are given on time and adequately.

Successful treatment of epilepsy and celiac disease with a gluten-free diet.

Celiac disease is a gluten-sensitive enteropathy, which recently has been described in association with epilepsy or other neurologic disturbances. This study describes a case of a 7-year-old female with intractable-to-treatment epilepsy and late-onset celiac disease, who was treated successfully with a gluten-free diet plus antiepileptic therapy. It is important for children with intractable cases of epilepsy and weight loss to undergo screening for celiac disease.

Oxcarbazepine monotherapy in benign childhood epilepsy with centrotemporal spikes: a clinical and cognitive evaluation.

We report on 70 patients (aged 5.2-11.6 years) newly diagnosed with benign childhood epilepsy with centrotemporal spikes (BECTS) who were assigned to oxcarbazepine (OXC) monotherapy. All of them underwent clinical and electroencephalographic examination at baseline and at 3- to 6-month intervals during the study. Psychometric assessment was performed at baseline and after 18 months of treatment with the WISC-III, Illinois Test of Psychomotor Abilities, DSM-IV, and Bender-Santucci test. The Mann-Whitney U test was used to describe differences in the frequency of abnormal findings: (1) at initial evaluation, comparing patients with a matched group of 45 healthy controls, and (2) after 18 months of OXC monotherapy, as an individual follow-up in the patient group. Cognitive assessment at baseline revealed mild learning disabilities in 9% of patients and 7% of controls; all participants had a normal intelligence quotient. During the follow-up, sustained cessation of seizures under medication was observed in 53% of patients; an additional 21% had some relapse but were subsequently rendered seizure free, 21% experienced a >50% improvement, and 5% showed no improvement. Normalization of interictal epileptiform activity was observed in 58% of patients, 35% showed an improvement in the grade of electroencephalographic pathology, and 7% manifested no change at all. The initial mildly weak scores in isolated cognitive domains did not deteriorate, and even improved in some cases, during the course of the study, with concomitant electroencephalographic improvement or normalization and effective seizure control. The results of this study suggest that OXC is effective in preventing seizures and normalizing electroencephalograms and seems to preserve cognitive functions and behavioral abilities as long-term monotherapy in children with typical BECTS.

Gastric emptying in children with cerebral palsy and gastroesophageal reflux.

Gastric emptying time is considered a factor in the increased frequency of gastroesophageal reflux in children with cerebral palsy. It is unknown if emptying time influences the severity of reflux. In this study, 76 cerebral palsy patients with reflux indicative symptoms were investigated by 24-hour pH monitoring. Reflux complications were also studied. Emptying time in children with reflux was investigated using gastric scintigraphy. Twenty-eight children with resistant asthma scanned for pulmonary aspiration were studied as control subjects for emptying time. Reflux was diagnosed in 51.3%; it was severe in 53.8%, moderate in 38.5%, and mild in 7.7%. Occurrence of reflux did not differ significantly among different forms of cerebral palsy or between males and females. The most frequent complications in reflux-positive patients were iron deficiency (51.3%), anemia (41.0%), malnutrition (33.3%), recurrent upper respiratory tract infections (28.2%), and low body weight (28.2%). Patients without reflux had less frequent complications. Gastric emptying time measured by gastric scintigraphy in 28 patients with reflux manifested no difference in comparison to the control group (P > 0.05). No relationship was found between emptying time and reflux severity (P > 0.05). In conclusion, reflux (moderate or severe) is common in children with cerebral palsy, frequently leading to complications but no delayed emptying time. The patients described in this report had no delayed emptying time. There was also no relationship between emptying time and severity of reflux.

Lissencephaly and mongolian spots in Hurler syndrome.

Hurler disease or syndrome is a disorder of mucopolysaccharide metabolism, inherited as an autosomal recessive trait. We describe a case of a 15-month-old female exhibiting with clinical and laboratory characteristics of the syndrome, central nervous system lesions (lissencephaly, excessive ventricular enlargement and Dandy Walker malformation with vermis atrophy, cerebellar cyst) and mongolian spots in the trunk and extremities. The combination of mongolian spots and severe central nervous system lesions in Hurler syndrome is considered a rare clinical occurrence, while the association with lissencephaly has never been reported.