phenylephrine-hydrochloride and Epilepsy

The ubiquitin-proteasome system facilitates the degradation of unstable or damaged proteins. UBR1-7, which are members of hundreds of E3 ubiquitin ligases, recognize and regulate the half-life of specific proteins on the basis of their N-terminal sequences ("N-end rule"). In seven individuals with intellectual disability, epilepsy, ptosis, hypothyroidism, and genital anomalies, we uncovered bi-allelic variants in UBR7. Their phenotype differs significantly from that of Johanson-Blizzard syndrome (JBS), which is caused by bi-allelic variants in UBR1, notably by the presence of epilepsy and the absence of exocrine pancreatic insufficiency and hypoplasia of nasal alae. While the mechanistic etiology of JBS remains uncertain, mutation of both Ubr1 and Ubr2 in the mouse or of the C. elegans UBR5 ortholog results in Notch signaling defects. Consistent with a potential role in Notch signaling, C. elegans ubr-7 expression partially overlaps with that of ubr-5, including in neurons, as well as the distal tip cell that plays a crucial role in signaling to germline stem cells via the Notch signaling pathway. Analysis of ubr-5 and ubr-7 single mutants and double mutants revealed genetic interactions with the Notch receptor gene glp-1 that influenced development and embryo formation. Collectively, our findings further implicate the UBR protein family and the Notch signaling pathway in a neurodevelopmental syndrome with epilepsy, ptosis, and hypothyroidism that differs from JBS. Further studies exploring a potential role in histone regulation are warranted given clinical overlap with KAT6B disorders and the interaction of UBR7 and UBR5 with histones.

Topics: Animals; Anus, Imperforate; Caenorhabditis elegans; Cell Line; Ectodermal Dysplasia; Epilepsy; Growth Disorders; Hearing Loss, Sensorineural; HEK293 Cells; Histones; Humans; Hypothyroidism; Intellectual Disability; Mice; Mutation; Neurodevelopmental Disorders; Nose; Pancreatic Diseases; Proteasome Endopeptidase Complex; Receptors, Notch; Signal Transduction; Ubiquitin-Protein Ligases

While olfactory hallucinations are relatively rare in epilepsy, a high prevalence (up to 42%) has been reported in one form - Transient Epileptic Amnesia (TEA). TEA is characterized by recurring amnestic seizures and is commonly associated with persistent interictal memory deficits. Despite reports of changes in smell, olfactory ability has not been objectively assessed in this group. The aim of this study was to measure olfactory ability in patients with TEA and explore whether olfactory symptoms relate to other clinical variables.. Fifty-five participants with TEA were recruited from The Impairment of Memory in Epilepsy project database. The presence of olfactory symptoms was obtained via case notes and clinical interview. Participants completed questionnaires to evaluate their olfaction and memory function subjectively. Olfactory ability was measured using the University of Pennsylvania Smell Identification Test (UPSIT). TEA participants' performance was compared to 50 matched healthy control participants. A subset of TEA participants (n=26) also completed a battery of memory tests including standard neuropsychological measures, and assessment of accelerated long-term forgetting and autobiographical memory.. Olfactory hallucinations were reported in 55% of patients with TEA. A significant reduction in smell identification (UPSIT) was found between patients with TEA and healthy controls (p<0.001). Epilepsy variables, including history of olfactory hallucinations, were not predictive of olfactory ability. Patients reported ongoing memory difficulties and performed below normative values on objective tests. While no correlation was found between objective measures of memory and olfactory performance, subjective complaints of route finding difficulty was associated with UPSIT score.. Impairments in odor identification are common in patients with TEA and exceed changes that occur in normal aging. Olfactory hallucinations occurs in approximately half of patients with TEA, but do not always coincide with reduced sense of smell. Olfactory impairment and interictal memory problems both occur frequently in TEA but are not closely associated.

Topics: Adult; Aged; Amnesia; Cohort Studies; Epilepsy; Female; Hallucinations; Humans; Male; Middle Aged; Neuropsychological Tests; Nose; Olfaction Disorders; Retrospective Studies; Smell

Meningocele and meningoencephalocele of the lateral wall of the sphenoidal sinus (LWSS) are rare lesions, crossing the borders of multiple disciplines such as ear-nose-throat, maxillofacial, and neurologic surgery. We reviewed our surgical experience to analyze the role of the endoscopic endonasal approach and consider these pathologies from different perspectives.. All consecutive cases of meningocele and meningoencephalocele of LWSS operated through an endoscopic endonasal approach from 1998 to 2015 in our institutions were collected. Medical history, focusing on previous episodes of cerebrospinal fluid leak, meningitis or seizures, was considered. The outcome was assessed considering the medical condition and the postoperative neuroimaging.. The series includes 23 patients (7 male, 16 female). Mean age was 52 years (26-73 years). Eleven cases were meningoencephaloceles and 12 meningoceles. A clear cerebrospinal fluid leak occurred on in 19 patients and was associated with meningitis in 3. Two were presenting a history of epilepsy. No complications were observed, but 1 case presented seizures on waking. At follow-up (mean 84 months, 4-167) each patient is in good clinical condition with no further episodes of leaking or seizures.. Endoscopic endonasal surgery is a safe and effective approach for meningocele and meningoencephalocele of LWSS; it allows resection of herniated tissue and repair of the osteodural defect. The favorable clinical outcome and the possible effectiveness on seizures lead us to support this approach as first minimally invasive treatment also in presence of epilepsy, as a first low risk epilepsy surgical procedure.

Topics: Adult; Aged; Cerebrospinal Fluid Rhinorrhea; Encephalocele; Epilepsy; Female; Headache; Humans; Incidental Findings; Magnetic Resonance Imaging; Male; Meningitis; Meningocele; Middle Aged; Neuroendoscopy; Nose; Retrospective Studies; Sphenoid Sinus; Tomography, X-Ray Computed

Epileptic seizures are followed by dynamic alterations in neurological function in the postictal period. Although the first observation of such phenomena dates back to Bravais who described postictal hemiparesis in 1827, this critical period of time after seizure offset has received little attention in the literature. In this article, we report some of the most important postictal signs, such as postictal hemiparesis, postictal nose wiping, postictal language dysfunction, postictal headache and postictal cognitive impairment. Summarizing our own experience of the postictal state in more than 160 patients with focal epilepsy, we conclude that postictal signs can provide reliable information for the localization of the seizure onset zone in patients with focal epilepsy. Since the lateralization and localization of the seizure onset zone has become a major issue for the presurgical evaluation of those patients, we argue that more attention should be paid to the postictal state during video EEG monitoring. Moreover, in an ambulatory setting, the postictal period and its related signs is usually the only part of an epileptic seizure that is accessible to the physician's examination and might therefore add some information to the differential diagnosis of paroxysmal events, such as epileptic or psychogenic seizures [published with videosequences].

Topics: Brain; Brain Mapping; Epilepsy; Functional Laterality; Hand; Headache; Hemianopsia; Humans; Memory Disorders; Nose; Paralysis; Seizures; Speech Disorders

Semiology is very useful in the diagnosis and classification of seizures. Some clinical signs occur primarily with specific localization-related epilepsies.. To evaluate postictal nose-rubbing as a potential diagnostic sign and a potential lateralizing or localizing indicator.. We reviewed presurgical prolonged video-EEG results of 50 consecutive patients with right temporal lobe epilepsy (TLE), 50 consecutive patients with left TLE, 50 consecutive patients with frontal lobe epilepsy, 11 consecutive patients with generalized epilepsy, and 100 consecutive patients with nonepileptic events. Videotapes of all events were reviewed independently by two investigators who were blinded to the results of the monitoring. The episodes of nose-rubbing and the hand with which the patient rubbed the nose were recorded.. Nose-rubbing occurred in 25 of 50 (50%) right TLE patients and in 21 of 50 (42%) left TLE patients. Approximately 90% of patients rubbed his or her nose with the ipsilateral hand. Nose-rubbing occurred in 5 of 50 (10%) frontal lobe epilepsy patients. Nose-rubbing was not seen in any patient with generalized epilepsy or nonepileptic events. Postictal nose-rubbing did not occur after secondarily generalized seizures.. Nose-rubbing is an easily observed phenomenon, has high interobserver reliability, and provides useful lateralizing information in patients with TLE. It was less frequently seen in extratemporal lobe epilepsy and was not seen after generalized seizures or nonepileptic events.

Topics: Adolescent; Adult; Aged; Brain; Child; Electroencephalography; Epilepsy; Female; Functional Laterality; Humans; Male; Middle Aged; Nose; Videotape Recording

A new case of Hernandez syndrome is described in a 16-year-old Brazilian girl. The syndrome consists mainly of psychomotor retardation, epilepsy, a bulbous nose and obesity.

Topics: Adolescent; Developmental Disabilities; Epilepsy; Female; Humans; Nose; Obesity; Psychomotor Performance; Syndrome

Bilateral periventricular nodular heterotopia (BPNH) is a recently recognized malformation of neuronal migration in which nodular masses of gray matter line the walls of the lateral ventricles. Most affected individuals are females with epilepsy and normal intelligence, but no other congenital anomalies. Studies in families with multiple affected individuals, always all females, have mapped one BPNH gene to chromosome Xq28. Several other BPNH syndromes associated with mental retardation and epilepsy but without significant dysmorphic facial features have been observed in males only, which may also be X-linked. This report describes a new syndrome with BPNH.. Clinical and MRI study and cognitive testing of two unrelated boys, aged 8 and 5.5 years, and review of the enlarging spectrum of syndromes associated with BPNH.. Similarities between the two boys are sufficient to delineate a new multiple congenital anomaly-mental retardation syndrome that consists of BPNH, regional cortical dysplasia, mild mental retardation, and frontonasal malformation.. The cause of this unusual syndrome is unknown; based on linkage of other BPNH syndromes to chromosome Xq28 and the report of possible X-linked inheritance of frontonasal malformation, we suspect the cause is genetic, with possible X-linked inheritance.

Topics: Abnormalities, Multiple; Cerebral Ventricles; Child; Child, Preschool; Choristoma; Epilepsy; Frontal Bone; Functional Laterality; Genetic Linkage; Humans; Intellectual Disability; Magnetic Resonance Imaging; Male; Nose; Syndrome; X Chromosome

We observed many patients with temporal lobe epilepsy (TLE) wiping their nose postictally, usually with the hand ipsilateral to their seizure focus. We wished to determine if this had lateralizing or localizing significance.. We retrospectively studied 87 patients: 47 with unilateral TLE defined by successful surgical outcome [30 with medial TLE (MTLE) and 17 with neocortical TLE (neoTLE)]; and 40 with extratemporal epilepsy (ExTLE). Videotapes of 319 complex partial seizures (CPS) without generalization were reviewed by 1 neurologist, blinded to patient identity, who recorded each episode of nosewiping and the hand with which it was performed.. With regard to localizing potential, postictal nosewiping (PINW) was significantly more common in patients with unilateral TLE than in those with ExTLE. In the TLE group, PINW within 60 s of electrographic seizure offset occurred in 60% of patients (28 of 47) and 43% of seizures (74 of 171). In the ExTLE group, PINW was noted in 33% of patients (13 of 40; p < 0.05 as compared with TLE) and 15% of seizures (22 of 148; p < 0.001). Similar results were obtained with PINW within 30 s of seizure offset. Although PINW was more frequent in MTLE than in neoTLE (67% of patients vs. 47%), this finding did not reach significance. With regard to lateralizing potential, in the TLE group, unilateral PINW (performed with a single hand only) within 60 s of seizure offset was observed in 53% of patients (25 of 47) and was performed with the hand ipsilateral to the seizure focus in 92% (23 of 25). Thirteen patients (9 with TLE) wiped their nose more than once with the same hand in a single seizure within 60 s of offset in 18 seizures; this was done with the hand ipsilateral to the seizure focus in all 18 instances (predictive value = 100%).. PINW is more common in unilateral TLE, particularly MTLE, than in ExTLE. PINW performed exclusively with one hand occurs in approximately 50% of patients with TLE and is highly predictive (92%) of seizure onset ipsilateral to the hand used, especially when it occurs repetitively. We hypothesize that ictal activation of the central autonomic nervous system, particularly the amygdala, results in ictal nasal secretions and causes nosewiping as the patient regains awareness postictally. The ipsilateral hand is used due to contralateral neglect or weakness.

Topics: Amygdala; Automatism; Autonomic Nervous System; Epilepsy; Epilepsy, Temporal Lobe; Functional Laterality; Humans; Hygiene; Mucus; Nasal Mucosa; Nose; Retrospective Studies; Temporal Lobe

The utility of nasopharyngeal (NP) recording in psychiatry is controversial. To assess its value, 302 NP recordings from patients with psychiatric illnesses were reviewed. Among the 81 patients whose electroencephalograms (EEGs) demonstrated spikes or sharp waves, 10 patients (12%) were found to have epileptic foci at the mesiobasal temporal region recorded exclusively by NP leads. However, all of these recordings showed additional independent epileptic foci detected by scalp electrodes. Five patients (6%) had epileptic discharges simultaneously recorded from NP and scalp electrodes. No recording showed all epileptic discharges to be exclusively recorded by NP leads. These findings suggest that although NP recording may not be absolutely required to determine if an EEG contains epileptiform discharges, in a psychiatric population, it may be useful to detect additional epileptic foci at the mesiobasal temporal region.

Topics: Electrodes; Electroencephalography; Epilepsy; Humans; Mental Disorders; Nose; Pharynx; Temporal Lobe

Topics: Child; Epilepsy; Female; Genes, Recessive; Humans; Intellectual Disability; Male; Nose; Pedigree; Syndrome

In experiments on animals, airflow through the nasal cavity elicits rhythmic synchronized activity that can trigger and/or elicit epileptic electrographic activities in the limbic structures of the brain. This could be demonstrated in studies of lower vertebrates (frogs and turtles). In the turtle the elicited paroxysmal activity often had the shape of regular high-voltage activity in the theta-frequency range (average frequency, 4.1 Hz). It was further proven in clinical experiments that nasal deep breathing with a closed mouth effectively activates epileptic electrographic phenomena of a temporal (limbic) origin. The activating effect was more pronounced on the side ipsilateral to the ventilated nasal meatus. It could also be evoked by air insufflation into the nasal cavity. This effect was suppressed by anesthesia of the mucous membrane in the upper nasal meatus. Possible mechanisms of this, probably reflex, phenomenon are discussed.

Topics: Animals; Electroencephalography; Epilepsy; Humans; Hyperventilation; Mouth Breathing; Nose; Rana temporaria; Reflex; Respiration; Turtles

Topics: Abnormalities, Drug-Induced; Adolescent; Dwarfism; Epilepsy; Eye Abnormalities; Female; Fingers; Humans; Hydantoins; Nose; Pregnancy; Pregnancy Complications; Skull

Topics: Adolescent; Anticonvulsants; Connective Tissue; Epilepsy; Face; Humans; Male; Nose

The electrographic respiratory response (ERR) was elicited by nasal air flow in the brain of the frog and turtle. It had the shape of a spindle of high voltage rhythmic activity and was propagated from the olfactory bulb predominantly into the ipsilateral hippocampal region in the frog and into the pyriform cortex in the turtle. In both animals, thalamic propagation of the ERR was also found. In both animals epileptic electrographic phenomena, were enhanced, created by local penicillin application. In the turtle epileptic electrographic manifestations were also elicited in the intact brain by simple nasal air insufflation. Diazepam (intraperitoneal administration) had no effect either on the ERR or on its triggering effect on epileptic phenomena. The possible physiological and pathophysiological interpretations of these findings are discussed.

Topics: Animals; Cerebral Cortex; Electroencephalography; Epilepsy; Hippocampus; Nose; Rabbits; Rats; Respiration; Turtles

A child in status epilepticus, who did not respond to intravenous diazepam, was treated with sodium valproate by naso-gastric tube. Subsequent clinical and encephalographic improvement appeared to be related to the sodium valproate, and its value in cases of status epilepticus is discussed.

Topics: Child; Epilepsy; Female; Humans; Intubation, Gastrointestinal; Nose; Valerates; Valproic Acid

Topics: Adult; Brain Diseases; Brain Neoplasms; Electrodes; Epilepsy; Epilepsy, Tonic-Clonic; Ethmoid Sinus; Frontal Lobe; Humans; Male; Meningioma; Middle Aged; Nose; Wakefulness

Topics: Cerebral Ventriculography; Child; Dental Enamel Hypoplasia; Electroencephalography; Epilepsy; Eye Abnormalities; Female; Fingers; Glaucoma; Hair; Humans; Intellectual Disability; Iris; Microphthalmos; Nose; Radiography; Toes; Tooth Discoloration