Immunologic and Inflammatory Aspects of Epilepsy
Epilepsy is a common neurological disorder affecting between 1 and 3% of the population with peak incidence in the extremes of life.1 While many structural, metabolic and genetic causes of epilepsy have been identified, a subset of cases without known or demonstrable cause is classified as idiopathic.2,3 As the knowledge of underpinning genetic mechanisms and central nervous system (CNS) immune dysfunction in epilepsies is constantly evolving, the group of cases currently diagnosed as “idiopathic epilepsy” is becoming increasingly narrower. (Source: Seminars in Pediatric Neurology)
Source: Seminars in Pediatric Neurology - October 16, 2014 Category: Neurology Authors: Ignacio Valencia, Divya S. Khurana Source Type: research

Experimental Studies in Epilepsy: Immunologic and Inflammatory Mechanisms
In this paper we review the literature based on experimental studies leading credence to a relationship between epilepsy and immune-mediated mechanisms linked to Central Nervous System (CNS) innate immunity. The brain innate immunity responses to neuronal injury or to excessive neuronal activity are mediated by resident microglia and astroglia, but also neurons play an immunomodulatory role. Antigens or antibodies applied to the brain trigger an epileptogenic and inflammatory response. Furthermore, seizure activity and status epilepticus elicit the production and release of pro-inflammatory cytokines and chemokines. (Sourc...
Source: Seminars in Pediatric Neurology - October 9, 2014 Category: Neurology Authors: Agustín Legido, Christos D. Katsetos Source Type: research

Status Epilepticus: Immunologic and Inflammatory Mechanisms
Status epilepticus (SE) can be difficult to treat, particularly if refractory, and lead to significant morbidity and mortality. Prolonged seizures are also a risk factor for the subsequent diagnosis of epilepsy. Activation of the immune system and inflammation are areas of recent interest in the field of epilepsy, and there is growing evidence that these may be involved in the pathogenesis of ongoing SE and subsequent epileptogenesis. We review the current data on this topic in both animal models and human disease. (Source: Seminars in Pediatric Neurology)
Source: Seminars in Pediatric Neurology - September 13, 2014 Category: Neurology Authors: Chandrabhaga Miskin, Daphne M. Hasbani Source Type: research

Status epilepticus: Immunologic and inflammatory Mechanisms of epilepsy
Status epilepticus can be difficult to treat, particularly if refractory, and lead to significant morbidity and mortality. Prolonged seizures are also a risk factor for the subsequent diagnosis of epilepsy. Activation of the immune system and inflammation are areas of recent interest in the field of epilepsy, and there is growing evidence that these may be involved in the pathogenesis of ongoing status epilepticus and subsequent epileptogenesis. We review the current data on this topic in both animal models and human disease. (Source: Seminars in Pediatric Neurology)
Source: Seminars in Pediatric Neurology - September 13, 2014 Category: Neurology Authors: Chandrabhaga Miskin, Daphne M. Hasbani Source Type: research

Generalized Epilepsies: Immunologic and Inflammatory Mechanisms
This article focuses on the inflammatory processes in patients with generalized epilepsies. We specifically review the data regarding West, Lennox-Gastaut, and Landau-Kleffner syndromes as they have generalized clinical or electroencephalogram features. And there is substantial evidence for a pathogenic implication of immune mechanisms in these epilepsies. Animal models and abnormalities in both cellular and humoral immunity support this hypothesis. They also appear to be particularly responsive to immunomodulatory therapies, which has raised the speculation that an unbalanced immune system may play an important role in th...
Source: Seminars in Pediatric Neurology - August 26, 2014 Category: Neurology Authors: Karen S. Carvalho, Diana J. Walleigh, Agustín Legido Source Type: research

Focal Epilepsies: Immunologic and Inflammatory Mechanisms
There is increasing evidence documenting activation of inflammatory processes in focal epilepsies. This review article summarizes current data regarding immune mediated inflammatory processes in patients with symptomatic partial epilepsies such as mesial temporal sclerosis, focal cortical dysplasia, and Rasmussen's encephalitis. We have also reviewed several neuronal surface antibody–associated syndromes, which have been recently described with focal seizures as an important part of clinical presentation, such as antibody-associated limbic encephalitis and N-methyl-d-aspartic acid receptor antibody syndrome. (Source:...
Source: Seminars in Pediatric Neurology - August 12, 2014 Category: Neurology Authors: Divya S. Khurana Source Type: research

Focal Epilepsy: Immunologic and Inflammatory Mechanisms
There is increasing evidence documenting activation of inflammatory processes in focal epilepsy. This review article summarizes current data regarding inflammatory processes in patients with symptomatic partial epilepsies such as mesial temporal sclerosis, focal cortical dysplasia, and Rasmussen's encephalitis. We have also reviewed several neuronal surface antibody–associated syndromes, which have been recently described with focal seizures as an important part of the presentation, such as antibody-associated limbic encephalitis and N-methyl-d-aspartic acid receptor antibody syndrome. (Source: Seminars in Pediatric Neurology)
Source: Seminars in Pediatric Neurology - August 12, 2014 Category: Neurology Authors: Divya S. Khurana Source Type: research

Immunomodulatory Treatments in Epilepsy
The role of immunity and inflammation appears to be an integral part of the pathogenic processes associated with some seizures, particularly with refractory epilepsy. Prompt treatment with immunotherapy may lead to better outcomes. Immune treatment options for treatment of epilepsy include therapies such as corticosteroids, immunoglobulins, plasmapheresis, or steroid-sparing drugs such as azathioprine. Recent options have included even more aggressive treatment with cyclophosphamide, anti–pre-B-lymphocyte monoclonal antibody rituximab, and monoclonal antibodies such as efalizumab or natalizumab, which are presently u...
Source: Seminars in Pediatric Neurology - August 8, 2014 Category: Neurology Authors: Joseph Melvin, H. Huntley Hardison Source Type: research

Epilepsy in Systemic Autoimmune Disorders
Autoimmunity and inflammation have been implicated as causative factors of seizures and epilepsy. Autoimmune disorders can affect the central nervous system as an isolated syndrome or be part of a systemic disease. Examples of systemic autoimmune disorders include systemic lupus erythematosus, antiphospholipid syndrome, rheumatic arthritis, and Sjögren syndrome. Overall, there is a 5-fold increased risk of seizures and epilepsy in children with systemic autoimmune disorders. Various etiologic factors have been implicated in causing the seizures in these patients, including direct inflammation, effect on blood vessels ...
Source: Seminars in Pediatric Neurology - July 31, 2014 Category: Neurology Authors: Ignacio Valencia Source Type: research

Delayed-Onset Movement Disorder and Encephalopathy After Oxycodone Ingestion
We present the case of a 14-year-old girl with a biphasic course after oxycodone ingestion. Clinically, she had a rapid return to baseline after initial ingestion and presented a week later with new-onset ballism, akathisia, and encephalopathy. Neuroimaging demonstrated bilateral globi pallidi and cerebellar lesions with a relative decrease of metabolite peaks on magnetic resonance spectroscopy. Her movement disorder was treated successfully with valproic acid and clonidine. Her cognitive functioning returned to baseline 3 months after ingestion. (Source: Seminars in Pediatric Neurology)
Source: Seminars in Pediatric Neurology - June 20, 2014 Category: Neurology Authors: Christopher W. Beatty, Ping-Ru Ko, Jason Nixon, Sidney M. Gospe Source Type: research

Editorial Comment: Two-Year-Old Boy With Recurrent Seizures, Abnormal Movements, and Central Hypoventilation
In this issue, Drs Cohen and Wong-Kisiel describe an illustrative case of severe N-methyl-D-aspartate receptor (NMDAR) encephalitis with a protracted clinical course. They describe a positive response to aggressive treatment following suboptimal response to first-line immunosuppressive therapies. The case illustrates some important aspects of the early diagnosis and treatment of NMDAR antibody–mediated encephalitis that can be challenging in young children. In these cases, important clues to the diagnosis could be missed or attributed to other possible etiologies. The discussion thoroughly summarizes the current know...
Source: Seminars in Pediatric Neurology - June 19, 2014 Category: Neurology Authors: Jan-Mendelt Tillema Source Type: research

Editorial Comment: Cerebellar Ataxia, Vertical Supranuclear Gaze Palsy, Sensorineural Deafness, Epilepsy, Dementia and Hallucinations in an Adolescent Male
The authors describe a case of Niemann-Pick disease type C, which features many typical findings. The history of difficulty with vertical gaze beginning at 2 years of age and the confirmation of a vertical supranuclear gaze palsy at 13 years, together with cerebellar dysfunction, epilepsy, cognitive decline, sensorineural hearing loss and spasticity should have pointed immediately to Niemann-Pick disease type C as the most likely diagnosis. It is not clear from the protocol if the patient had splenomegaly or if imaging studies were performed to seek evidence of organomegaly. If splenomegaly was present, the diagnosis would...
Source: Seminars in Pediatric Neurology - June 19, 2014 Category: Neurology Authors: Marc C. Patterson Source Type: research

Editorial Comment: Unilateral Visual Loss in a Previously Healthy 15-Year-Old Girl: Monosymptomatic Neuromyelitis Optica?
Dr Kerrigan et al describe an interesting case of isolated unilateral optic neuritis with typical clinical, magnetic resonance imaging (MRI), and electrophysiological evidence in a pediatric patient. The patient tested positive for aquaporin-4 antibodies in both the serum and cerebrospinal fluid. No other imaging or clinical findings were described to be present that would suggest any additional diencephalic, brainstem, or cerebral involvement, where aquaporin-4 (AQP4) pathology can be seen in addition to the optic nerves and spinal cord. Cerebrospinal fluid analysis showed the presence of oligoclonal bands, in itself not ...
Source: Seminars in Pediatric Neurology - June 18, 2014 Category: Neurology Authors: Jan Mendelt Tillema Source Type: research

Editorial Comment: Ataxia, Ophthalmoplegia, and Impairment of Consciousness in a 19 Month-Old American Boy
The authors describe a classic neurologic syndrome in an unusual setting. Wernicke encephalopathy is most commonly encountered in malnourished adults, particularly those who abuse alcohol. It is not generally high in the differential diagnosis of childhood disorders, particularly in children who are otherwise ostensibly well, but it is critical to diagnose, owing to its potential reversibility with early treatment. This elegant report beautifully outlines the diagnostic process, differential diagnosis, and recognition of the key findings—the combination of acute ataxia and ophthalmoplegia with altered mental status a...
Source: Seminars in Pediatric Neurology - June 18, 2014 Category: Neurology Authors: Marc C. Patterson Source Type: research

Editorial Comment
This case with delayed deterioration, bilateral globus pallidus necrosis, and neurologic symptoms that resolved over time is very interesting and can be discussed from a number of different angles. The occurrence of delayed necrosis of the basal ganglia following a hypoxic-ischemic injury or a hypoxic injury alone has been known for a long time. The role of the intoxicating agent is not clearly delineated in this phenomenon, and in my view, it is probable that the overlap in the distribution of involvement is such that the elaborate descriptions of the distribution of injury with any particular intoxicating agent (with the...
Source: Seminars in Pediatric Neurology - June 11, 2014 Category: Neurology Authors: John B. Bodensteiner Source Type: research

Childhood Primary Angiitis of the Central Nervous System With Metachronous Hemorrhagic Infarcts: A Postmortem Study With Clinicopathologic Correlation
This neuropathologic case study illustrates the discovery of metachronous hemorrhagic infarcts insinuating round mass-like lesions by magnetic resonance imaging in the setting of childhood primary angiitis of the central nervous system (cPACNS) raising diagnostic awareness of this unusual presentation in a clinical and neuroimaging context. The report underscores the importance of recurrent vasculitis-induced ischemic brain damage as a pathologic correlate of relapsing cPACNS and offers a critical reappraisal of common imitators as well as a clinicopathologic approach to differential diagnosis. Attention is drawn to the ca...
Source: Seminars in Pediatric Neurology - June 9, 2014 Category: Neurology Authors: Christos D. Katsetos, Erica Poletto, Kathryn E. Kasmire, Diana Walleigh, Indira Kumar, Judy Mae Pascasio, Agustin Legido, Donald P. Goldsmith Source Type: research

Note From the Editor
The publication of case studies in one form or another is a time-honored tradition in medical education. Much of clinical medicine is taught through the use of this format. Still, there are few journals that can spare space for case studies and even fewer that can devote an entire issue to a collection of case studies. The Seminars has published 4 case studies issues in the last 20 years, and they have all been quite popular among our readership. This issue will be the fifth and last of the case studies issues during my tenure as editor in chief (EIC) of the Seminars. Looking back at the earlier case studies issues, it is ...
Source: Seminars in Pediatric Neurology - June 9, 2014 Category: Neurology Authors: John B. Bodensteiner Source Type: research

A 4-Year-Old Nigerian Boy With Cerebral Palsy?
A four year old with a diagnosis of congenital infection leading to cerebral palsy is presented. The patient instead has a condition called Leukoencephalopathy with bilateral temporal lobe cysts which can be differentiated from congenital CMV by the clinical and MRI findings. (Source: Seminars in Pediatric Neurology)
Source: Seminars in Pediatric Neurology - May 22, 2014 Category: Neurology Authors: John B. Bodensteiner Source Type: research

Editorial Comment: An Unusual Cause of Peroneal Neuropathy
This article by Dr. Ananth and colleagues reports a patient being evaluated for symptoms consistent with a peripheral neuropathy. In addition, the patient developed an arteriovenous fistula. Genomic testing subsequently identified a COL31A mutation, which is known to be associated with Ehlers-Danlos syndrome (EDS) of the vascular type. (Source: Seminars in Pediatric Neurology)
Source: Seminars in Pediatric Neurology - May 16, 2014 Category: Neurology Authors: Gerald Bradley Schaefer Source Type: research

Editorial Comment: Fraternal Twins With Autism, Severe Cognitive Deficit, and Epilepsy: Diagnostic Role of Chromosomal Microarray Analysis
This article by Dr. Imitola and colleagues reports a case of monozygotic twins with pathogenic copy-number changes that include biallelic deletions of the neurexin-1 (NRXN1) gene. This case wonderfully highlights several of the salient aspects of the genetic features of autism. First, it is worth emphasizing that autism is indeed a neurogenetic disorder. In fact, the reported heritability of autism approaches 0.9 (90%). It is always important to emphasize this fact to families and to continue to advocate for timely and appropriate immunizations of all children—not hindered by the unsubstantiated fear of immunization-...
Source: Seminars in Pediatric Neurology - May 15, 2014 Category: Neurology Authors: G. Bradley Schaefer Source Type: research

Editorial Comment: The Janus of Rasmussen Encephalitis: Never a Friendly Face
Rasmussen encephalitis (RE) is a devastating but important cause of medically intractable epilepsy in children, first described by Rasmussen et al in 1958 at the Montreal Neurological Institute. Since then, there has been progress in our understanding of the clinical evolution and pathology. However, progress in comprehending the underlying triggers, pathophysiology, and effective early therapies has been disappointing. (Source: Seminars in Pediatric Neurology)
Source: Seminars in Pediatric Neurology - May 15, 2014 Category: Neurology Authors: Elaine Wirrell Source Type: research

Brainstem Tegmental Necrosis and Olivary Hypoplasia: Raising Awareness of a Rare Neuropathologic Correlate of Congenital Apnea
This report raises awareness of the rare lethal entity of brainstem tegmental necrosis and olivary hypoplasia and its nosological relationship to the Möbius syndrome in the context of differential diagnosis of congenital apnea owing to central respiratory dysfunction. (Source: Seminars in Pediatric Neurology)
Source: Seminars in Pediatric Neurology - May 8, 2014 Category: Neurology Authors: Christos D. Katsetos, Carol E. Anderson, Miguel A. Guzman, Judy Mae Pascasio, Jean-Pierre de Chadarévian, Agustin Legido Source Type: research

Bizarre Semiology and Medically Intractable Seizures
A 15-year-old right hand–dominant young man with medically intractable epilepsy presented to our center to be assessed for surgical candidacy. His seizures began at 5 years of age. Semiology consisted of manual motions where he would grab his groin and rock back and forth. These events were witnessed during the day and lasted for 20-30 seconds. Seizure frequency was regular but not more often than twice per day. During the episodes, he seemed aware, and there was no postictal confusion. Multiple medication trials were tried, and he ultimately achieved successful control with carbamazepine monotherapy and remained se...
Source: Seminars in Pediatric Neurology - May 5, 2014 Category: Neurology Authors: Kamilia Nozile-Firth, Elaine Wirrell, Caterina Giannini Source Type: research

A 12-Year-Old African American Girl With Subacute Bilateral Ophthalmoplegia
A twelve-year-old African-American female presented with two week history of progressively worsening headache and fatigue, and vision difficulties for the past week. The physical examination was normal. The neurological evaluation was normal, except for cranial nerves (CN) testing, which showed bilateral restriction of adduction (CN III) and up gaze (CN IV) motions, vertical nystagmus, and left side facial paresis of central origin (CN VII). The bilateral exotropia and ophthalmoplegia are characteristics of WEBINO (Wall-Eyed Bilateral Intranuclear Ophthalmoplegia) syndrome, associated to a brain stem structural lesion. The...
Source: Seminars in Pediatric Neurology - May 1, 2014 Category: Neurology Authors: Amir Bar, Jacqueline Urbine, Yasmine Bahora, Meghan Berkenstock, Jennifer Vodzak, Hamalatha Guruprasad, Manisha Sinha, Thair Abed, Agustín Legido Source Type: research

Fraternal Twins With Autism, Severe Cognitive Deficit, and Epilepsy: Diagnostic Role of Chromosomal Microarray Analysis
We report 2 siblings with biallelic deletions, both of which affect the promoter region and exons 1-5 in the α-NRXN1 isoform, which has a role in the Ca2+-dependent release of neurotransmitters in the central nervous system. Our cases expand the phenotype of biallelic α NRXN 1 mutations and emphasize the important role of NRXN1 in autism and intellectual disability. Chromosomal microarray analysis should be the clinical standard in all specialties for first-tier genetic testing in autistic spectrum disorders. (Source: Seminars in Pediatric Neurology)
Source: Seminars in Pediatric Neurology - May 1, 2014 Category: Neurology Authors: Jaime Imitola, Diana Walleigh, Carol E. Anderson, Reena Jethva, Karen S. Carvalho, Agustin Legido, Divya S. Khurana Source Type: research

Unilateral Visual Loss in a Previously Healthy 15-Year-Old Girl: Monosymptomatic Neuromyelitis Optica?
We report a previously healthy 15 year old girl with acute onset of unilateral visual loss consistent with a diagnosis of monosymptomatic optic neuritis. Her symptoms responded well to the use of high-dose intravenous methylprednisolone. With very brief follow-up (2 months) she has had no subsequent difficulties. However, testing was positive for the presence of anti-aquaporin-4 antibodies in both serum and cerebrospinal fluid, which have been associated with neuromyelitis optica (NMO). While NMO antibodies lack complete sensitivity, there is high degree of specificity. Our patient does not meet currently accepted diagnost...
Source: Seminars in Pediatric Neurology - April 28, 2014 Category: Neurology Authors: John F. Kerrigan, Christina Chrisman, Reena Gogia Rastogi Source Type: research

Editorial Comment: Recurrent Episodes of Weak Spells in a 15 Year Old Boy
This case report with the rather extensive discussion does not require much comment but there are 2 additional points I wish to make: This patient was referred to a neurologist by the cardiologist with the request that he evaluate and recommend therapy for the episodes of weakness only to be told that this was not periodic paralysis (PP), as the K level was not altered during the spells. (Source: Seminars in Pediatric Neurology)
Source: Seminars in Pediatric Neurology - April 25, 2014 Category: Neurology Authors: John B. Bodensteiner Source Type: research

Editorial Comment: A 19 Month Old Girl of South Indian Parents Presented to a General Pediatric Clinic For Evaluation of Global Developmental Regression
Although this case is not unique in any way, it brings up 2 things I wish to note: Whether you support the process of preconception gene testing, the fact is that with meticulous application of carrier testing for Tay-Sachs disease in prospective parents, the Jewish people have been able to decrease the incidence of the disease to a remarkable extent. So much so that in the last 20 years all the cases of this disease I have seen are in non-Jewish families. (Source: Seminars in Pediatric Neurology)
Source: Seminars in Pediatric Neurology - April 25, 2014 Category: Neurology Authors: John Bodensteiner Source Type: research

WITHDRAWN: Ataxia, Ophthalmoplegia, and Impairment of Consciousness in a 19 Month-old American Boy
The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.spen.2014.04.015. The duplicate article has therefore been withdrawn.The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. (Source: Seminars in Pediatric Neurology)
Source: Seminars in Pediatric Neurology - April 21, 2014 Category: Neurology Authors: Gediminas Gliebus, Eric N. Faerber, Ignacio Valencia, Divya S. Khurana, Sabina B. Singh, Agust ín Legido Source Type: research

Ataxia, Ophthalmoplegia, and Impairment of Consciousness in a 19 Month-old American Boy
A 19-month old white Pennsylvanian boy, with an unremarkable past-medical history, presented to our hospital with a 3 week history of non-bloody, non-bilious emesis up to five times a day and non-bloody diarrhea. Ten days prior to admission his gait became progressively unsteady until he finally refused to walk. One day prior to admission he developed difficulty moving his eyes. The patient was hypoactive. History, physical and neurological examination, blood and cerebrospinal (CSF) fluid studies and neuroimaging studies ruled out the most frequent causes of acute ataxia (Table 1). (Source: Seminars in Pediatric Neurology)
Source: Seminars in Pediatric Neurology - April 21, 2014 Category: Neurology Authors: Gediminas Gliebus, Eric N. Faerber, Ignacio Valencia, Divya S. Khurana, Sabina B. Singh, Agustín Legido Source Type: research

Editorial Comment: Stroke Following Chiropractic Manipulation
I think this is a very interesting case with a very well done discussion of the incidence and mechanisms involved in the ischemic arterial strokes following manipulation of the neck. I have had an interest in this subject, and for that matter, the larger subject of vertebral artery distribution strokes in children since I was a resident some 40 years ago. We had a young woman in her early 20s come to the hospital with a lateral medullary infarction secondary to chiropractic manipulation of her neck when I was the senior resident on the neurology inpatient service. This led to some exploration of the literature and resulted...
Source: Seminars in Pediatric Neurology - April 21, 2014 Category: Neurology Authors: John B. Bodensteiner Source Type: research

WITHDRAWN: Ataxia, Ophthalmoplegia, and Impairment of Consciousness in a 19 Month-old American Boy
The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.spen.2014.04.015. The duplicate article has therefore been withdrawn.The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. (Source: Seminars in Pediatric Neurology)
Source: Seminars in Pediatric Neurology - April 20, 2014 Category: Neurology Authors: Gediminas Gliebus, Eric N. Faerber, Ignacio Valencia, Divya S. Khurana, Sabina B. Singh, Agust ín Legido Source Type: research

Case of a Two-Year-Old Boy With Recurrent Seizures, Abnormal Movements, and Central Hypoventilation
We present a case of a 2 year-old boy with anti-NMDAR encephalitis to illustrate and discuss the differences in neurological presentation, frequency of symptoms, and association with underlying tumor between children and adults. (Source: Seminars in Pediatric Neurology)
Source: Seminars in Pediatric Neurology - April 18, 2014 Category: Neurology Authors: Alexander L. Cohen, Lily C. Wong-Kisiel Source Type: research

A 7-Year-Old Child With Chronic Droopy Eyes, Weakness in Head-Neck Control, and an Abnormal Gait
Our patient is a 7-year-old girl, who presented at the age of 3 years with features of droopy eyes, weakness in head-neck control, inability to hop and jump, and an abnormal gait. She was initially evaluated in an outside hospital (OSH) occupational safety and health and treatment with pyridostigmine with suspicion of myasthenia gravis. She was then referred to our center for further evaluation. At the time of her hospitalization, she was reported to have improvement in her ptosis and stamina with pyridostigmine, without much benefit in her gross motor activities, inability to run and jump, and difficulty in getting up fro...
Source: Seminars in Pediatric Neurology - April 18, 2014 Category: Neurology Authors: Sonika Agarwal, Timothy E. Lotze, Suzanne L. Woodbury Source Type: research

Increasing Blurriness of the Borders Between Focal and Generalized as Well as Cryptogenic and Idiopathic Epilepsies in Defining the Role for Focal Epilepsy Surgery
This case studies issue includes 2 excellent, intriguing case reports. The title of the case report by Wirrell is a little confusing, as following the surgical workup, no surgery ensued once the diagnosis of the syntaxin binding protein 1 gene c901delC mutation had been made. Thorough workup to that point had localized fairly well the seizures to be arising from the left temporoparietal region. In view of the genetic diagnosis and good response to vigabatrin, he was not considered to be a surgical candidate. However with recent, rapid advances in diagnosing genetic diseases in not just epilepsy but numerous disorders, many...
Source: Seminars in Pediatric Neurology - April 18, 2014 Category: Neurology Authors: Yu-Tze Ng Source Type: research

Temporoparietal Resection in a Patient With Landau-Kleffner Syndrome
Landau-Kleffner syndrome (LKS) was originally described by Landau, a neurologist, and Kleffner, a speech pathologist, in 1957 as an epileptic disorder with an acquired aphasia. LKS is a childhood epileptic encephalopathy on the electroclinical spectrum of electrical status epilepticus in sleep (ESES). ESES is an electrographic pattern in which there is significant activation of spike wave discharges throughout slow wave sleep. LKS is an electroclinical syndrome presenting with language regression, seizures, and behavior abnormalities with the electroencephalography (EEG) findings of ESES. Other related syndromes include co...
Source: Seminars in Pediatric Neurology - April 18, 2014 Category: Neurology Authors: Anthony Fine, Katherine Nickels Source Type: research

Editorial Comment: Intractable Epilepsy, Hemispheric Malformation and Generalized EEG Abnormalities
This case addresses relevant practical issues in the evaluation of children with refractory epilepsy. Importantly, it generates the discussion about how to define the type of epilepsy. Until recently, it has been thought that focal brain lesions are usually associated with focal electroencephalographic (EEG) abnormalities, and that generalized EEG abnormalities defined generalized epilepsy. This is not always the case, and it has important practical therapeutic implications. (Source: Seminars in Pediatric Neurology)
Source: Seminars in Pediatric Neurology - April 18, 2014 Category: Neurology Authors: Agustin Legido Source Type: research

Intractable Epilepsy, Hemispheric Malformation, and Generalized Electroencephalography Abnormalities
We present a case of a young boy with a large hemispheric dysplasia, generalized EEG abnormalities and intractable epilepsy who achieved seizure freedom and markedly improved cognitive outcome after functional hemispherectomy (Source: Seminars in Pediatric Neurology)
Source: Seminars in Pediatric Neurology - April 18, 2014 Category: Neurology Authors: Leeda Ahmadi, Elaine Wirrell Source Type: research

The Janus-faced nature of Rasmussen’s Encephalitis
Rasmussen encephalitis (RE) is an inflammatory unilateral progressive medically refractory epilepsy associated with hemiparesis, cognitive dysfunction, and hemispheric atrophy. Here, we present 2 cases from our institution that demonstrate the dual nature of RE in 2 similarly aged children. Overall, 2 types of RE have been described: type 1 has a short prodromal phase and more explosive onset and type 2 has a longer prodromal of partial seizures followed by hemiparesis and atrophy. Younger patients are more likely to fit into the type 1 presentation and have been described as more likely to have dual pathology. Perhaps the...
Source: Seminars in Pediatric Neurology - April 17, 2014 Category: Neurology Authors: Craig Press, Adam Wallace, Kevin E. Chapman Source Type: research

Arm Weakness in a Child Following Chiropractor Manipulation of the Neck
A 6-year-old right-handed boy presents to the clinic with left arm weakness that developed 6 months previously. At that time, the patient was on his way to see his primary care physician for a sinus infection when he was “diverted” by his grandfather to see a chiropractor instead. There was some degree of spinal manipulation of the neck without any immediate pain being reported. The following evening, the patient woke with complaints of left arm tingling and numbness. He subsequently developed gradual weakness of the left arm over the next 7 days before the family sought medical care. He was seen by a practitio...
Source: Seminars in Pediatric Neurology - April 17, 2014 Category: Neurology Authors: Stephen R. Deputy Source Type: research

Ataxia, Ophthalmoplegia, and Impairment of Consciousness in a 19-Month-Old American Boy
A 19-month-old, white, Pennsylvanian boy, with an unremarkable medical history, presented to our hospital with a 3-week history of nonbloody, nonbilious emesis up to 5 times a day and nonbloody diarrhea. Ten days before admission, his gait became progressively unsteady, until he finally refused to walk. A day before admission, he found it difficult to move his eyes. The patient was hypoactive. History, physical and neurologic examination, blood and cerebrospinal (CSF) fluid studies, and neuroimaging studies ruled out the most frequent causes of acute ataxia. The etiology of bilateral, complete ophthalmoplegia was also take...
Source: Seminars in Pediatric Neurology - April 16, 2014 Category: Neurology Authors: Gediminas Gliebus, Eric N. Faerber, Ignacio Valencia, Divya S. Khurana, Sabina B. Singh, Agustín Legido Source Type: research

Cerebellar Ataxia, Vertical Supranuclear Gaze Palsy, Sensorineural Deafness, Epilepsy, Dementia, and Hallucinations in an Adolescent Male
We encountered an adolescent male with cerebellar ataxia since age 11, difficulty in vertical gaze from age 2, leg weakness since age 10, and partial epilepsy since age 8. At age 14, he developed visual and auditory hallucinations, as well as mild sensorineural deafness. He was evaluated as having a mitochondrial disorder. No common mitochondrial DNA mutations were detected in the blood. Muscle biopsy revealed nonspecific changes and normal respiratory chain enzyme complexes. He developed progressive cognitive decline leading to diagnosis of dementia at age 15, and intractablepartial epilepsy persisted despite treatment wi...
Source: Seminars in Pediatric Neurology - April 14, 2014 Category: Neurology Authors: Chang-Yong Tsao Source Type: research

Recurrent Episodes of Weak Spells in a 15-Year-Old Boy
A 15-year-old boy was referred for evaluation of “weak spells” since early childhood. The frequency of these episodes was on an average once a month, and their duration was variable from 4-6 hours to 1-2 days. There was no correlation to dietary intake, prior physical activity, or time of the day. During these spells, there was no reported pain. He experienced difficulty in standing, walking, climbing stairs, and raising his arms over his head. There were no associated cardiac or respiratory symptoms and no reported speech or swallowing difficulties during these spells. These spells would abort spontaneously, a...
Source: Seminars in Pediatric Neurology - April 14, 2014 Category: Neurology Authors: Radhika Dhamija, John B. Bodensteiner Source Type: research

Early-Onset Focal Seizures and Spasms—Is it Surgical?
A 6-month-old boy presented to our center for presurgical workup for his intractable seizures. He was born to a 22-year-old gravida 1 mother at 39 weeks of gestation by scheduled cesarean delivery because of a history of maternal herpes virus infection. His mother had been treated with valaciclovir in the past few weeks of her pregnancy and had no noted lesions. Additionally, she had experienced persistent nausea throughout most of the pregnancy for which she was treated with ondansetron. (Source: Seminars in Pediatric Neurology)
Source: Seminars in Pediatric Neurology - April 11, 2014 Category: Neurology Authors: Elaine Wirrell Source Type: research

A 19-Month-Old Girl of South Indian Parents Presented to a General Pediatric Clinic for Evaluation of Global Developmental Regression
A19-month-old girl of South Indian parents presented to a general pediatric clinic for evaluation of global developmental delay. The infant׳s father was the maternal uncle of the infant׳s mother; the maternal great-grandparents were uncle and niece. The child was delivered at term by cesarean for fetal heart decelerations following an uneventful pregnancy to her primiparous 27-year-old mother. The perinatal course was unremarkable. (Source: Seminars in Pediatric Neurology)
Source: Seminars in Pediatric Neurology - April 11, 2014 Category: Neurology Authors: Daniel Kenney, Andrea C. Wickremasinghe, Nusheen Ameenuddin, Marc C. Patterson Source Type: research

A Newborn With Complex Skeletal Abnormalities, Joint Contractures, and Bilateral Corneal Clouding With Sclerocornea
A newborn presented to genetics with complex skeletal abnormalities, joint contractures, and bilateral corneal clouding with sclerocornea. The patient survived for 8 months before succumbing to respiratory failure. Exome sequencing revealed a compound heterozygous mutation in theB3GALT6gene. Mutations in this gene have been associated with both Ehlers- Danlos syndrome, progeroid type 2 and spondyloepimetaphyseal dysplasia with joint laxity type 1. These diagnoses encompass the skeletal and joint findings. Our patient expands the phenotype of these diagnoses, as anterior segment eye anomalies have not been described with ei...
Source: Seminars in Pediatric Neurology - April 11, 2014 Category: Neurology Authors: Elizabeth A. Sellars, Katherine A. Bosanko, Tiffany Lepard, Adolfo Garnica, Gerald Bradley Schaefer Source Type: research

An Unusual Cause of Peroneal Neuropathy
We discuss the case of a teenage girl who presented with neurologic symptoms suggestive of a peripheral neuropathy, before the development of a central arteriovenous fistula. Electromyography and nerve conduction studies indicated peroneal motor neuropathy, but her comprehensive genetic study results were negative for common Charcot-Marie-Tooth mutations. After 2 years of stable symptoms, she presented with unilateral throbbing headache and tinnitus. Magnetic resonance angiography revealed a carotid cavernous fistula, which was confirmed with conventional angiography. A successful coil embolization of the fistula was perfo...
Source: Seminars in Pediatric Neurology - April 11, 2014 Category: Neurology Authors: Amitha L. Ananth, Yaping Yang, Seema R. Lalani, Timothy B. Lotze Source Type: research

A 7-Year-Old Girl With Hypertrophic Cardiomyopathy and Progressive Scoliosis
We report a 7 year old girl who was evaluated for progressive thoracolumbar scoliosis and hypertrophic cardiomyopathy. Neurological examination was found to be abnormal and significant for absent reflexes and weakness distally in lower extremities and positive Romberg sign. Electromyogram showed length-dependent, axonal, sensorimotor polyneuropathy. Frataxin levels were low at 3ng/mL. Molecular testing for Friedreich ataxia showed significantly expanded GAA repeats at 799 (abnormal>67 GAA repeats) on one allele and a heterozygous disease causing mutation, c.317T>C (p.Leu106Ser) on the other allele, confirming the dia...
Source: Seminars in Pediatric Neurology - April 7, 2014 Category: Neurology Authors: Radhika Dhamija, Salman Kirmani Source Type: research

Friedreich Ataxia
The advancements in the understanding of the genetic basis of Friedreich ataxia have made it more important than ever to recognize the early manifestations. The cardiac involvement has been known almost since the early description of the disease, but the nature and severity of the early cardiac involvement has been less well appreciated until recently. I would only make 2 points about the case: (Source: Seminars in Pediatric Neurology)
Source: Seminars in Pediatric Neurology - April 4, 2014 Category: Neurology Authors: John B. Bodensteiner Source Type: research