Neurophysiologic intraoperative monitoring (NIOM) in pediatric patients with polyneuropathy.

PURPOSE: Neurophysiologic intraoperative monitoring (NIOM) abnormalities during scoliosis surgery led to a diagnosis of Friedreich's ataxia in this illustrative case. This prompted the retrospective examination of NIOM for pediatric scoliosis surgery in polyneuropathy patients. METHODS: Among patients who underwent scoliosis surgery in 2010-2017, there were six polyneuropathy patients identified. Their clinical history and baseline NIOM data were reviewed. RESULTS: Scoliosis accompanied Charcot-Marie-Tooth disease, Friedreich's ataxia, and ataxia telangiectasia. Some patients with no recorded somatosensory evoked potentials (SEPs) exhibited motor evoked potentials (MEPs); no patients with absent MEPs had SEPs present. NIOM modifications included SEP stimulation rate; type of SEP electrodes used; train parameters for MEP acquisition; and sweep speed. CONCLUSIONS: This sample of NIOM data for previously monitored scoliosis cases in children with polyneuropathy allowed investigation of patterns of findings and troubleshooting attempts to optimize monitoring. Attentiveness to pertinent medical history prepared the NIOM team to change typical recording parameters based on underlying polyneuropathy. A multimodality approach provided useful information as several of these cases would have been unmonitorable with use of SEPs alone. As for the case described, the awareness of NIOM patterns in polyneuropathy may guide evaluations of patients with presumed idiopathic scoliosis who have unrecognized polyneuropathy.

Signs of autonomic arousal precede tilt-induced psychogenic nonsyncopal collapse among youth.

Characterizing the physiologic changes leading up to psychogenic nonsyncopal collapse (PNSC) may help to elucidate the processes that cause paroxysmal functional neurological symptom disorders and to clinically distinguish PNSC from syncope. Thus, we aimed to characterize preictal sweat rate, heart rate, and systolic blood pressure changes among patients with tilt-induced PNSC compared to patients with tilt-induced neurally mediated syncope. The presence of increased preictal sweating was compared between groups. Heart rates and systolic blood pressures were compared from the recumbent and tilted baselines to the periods 120 s and 30 s prior to PNSC and syncope. Patients with PNSC (n = 44) were more likely than patients with syncope (n = 44) to have preictal increases in sweating, n = 31 (70.5%) versus n = 21 (47.7%), p = 0.03, although all patients with syncope eventually developed a sweat response. Comparing the recumbent baseline to the period 30 s prior to PNSC, blood pressure (112 ±â€¯9 versus 129 ±â€¯13 mmHg, p < 0.001) and heart rate (76 ±â€¯12 versus 119 ±â€¯22 bpm, p < 0.001) increased. Similarly, comparing the tilted baseline to the period 30 s prior to PNSC, blood pressure (118 ±â€¯12 versus 129 ±â€¯13 mmHg, p < 0.001) and heart rate (95 ±â€¯15 versus 119 ±â€¯22 bpm, p < 0.001) increased. Preictal blood pressure and heart rate differed significantly between patients with PNSC and patients with syncope. In conclusion, signs of autonomic arousal (increased sweating, heart rate, and blood pressure) often precede tilt-induced PNSC. Sweating prior to fainting may not be useful in distinguishing PNSC from neurally mediated syncope.

Sweat patterns differ between tilt-induced reflex syncope and tilt-induced anxiety among youth.

PURPOSE: Profound sweating can occur with reflex-syncope and with emotional distress, but little is known about the similarities and differences between these sweat responses when they occur during orthostatic challenge. We sought to characterize and compare the sweat patterns related to tilt-induced syncope, presyncope, anxiety, and normal tilt testing. METHODS: In a prospective observational study, quantitative sweat rate was measured from the abdomen, forearm, ankle, and thigh during head-upright tilt. Sweat characteristics were compared across tilt diagnoses of syncope, presyncope, anxiety, and normal testing. When anxiety and syncope/presyncope occurred during the same study (separated by ≥6 min), both were diagnosed. RESULTS: Our cohort comprised150 patients (15.1 ± 2.3 years; 82.9 % female) with 156 diagnoses: 76 with reflex-syncope, 31 with presyncope, 23 with anxiety, and 26 with normal results. All syncope/presyncope patients and 20 (87 %) of the anxiety patients had corresponding sweat responses. Minimal or negligible sweating occurred among patients with normal tests. Neither basal sweat (19.4 ± 4.7 versus 18.3 ± 3.7 versus 18.5 ± 3.7 nL/min/cm(2)) nor peak sweat (171 ± 47.4 versus 149.4 ± 64.4 versus 154.4 ± 59.2 nL/min/cm(2)) differed between patients with syncope, presyncope, or anxiety, p = .32 and p = .12, respectively. However, the qualitative sweat patterns related to syncope/presyncope (diffuse, smoothly contoured, symmetrical, single peaks) differed considerably from the sweat patterns related to anxiety (heterogeneous, asymmetrical, roughly contoured single-peak, multi-peak, or progressive sweat changes). CONCLUSIONS: The sweat patterns related to syncope/presyncope are distinguishable from the sweat patterns related to anxiety. Recognition of the different sweat patterns can inform how signs and symptoms are interpreted during clinical orthostatic challenge.

Tuberous Sclerosis Complex.

Affecting approximately 1 per 6000-10,000 individuals, tuberous sclerosis complex (TSC) is a neurocutaneous disorder that is not only uncommon but at risk to go underrecognized. Similar to other phakomatoses, TSC is a disorder of cellular proliferation and migration producing hamartomas-benign tumors or malignant cancers affecting the skin and brain-and also involving the heart, kidneys, lungs and eyes in ways that can vary across the lifetime. It also occurs and varies across generations. Among medical subspecialists, the pediatric neurologist is often responsible for making the initial diagnosis when the affected individual presents with infantile spasms or another early-onset epilepsy syndrome. In recent decades, the identification of the responsible genes and gene products forming the mechanistic target of rapamycin complex, previously termed the mammalian target of rapamycin, not only has expanded our understanding of tuberous sclerosis pathophysiology, but has also inspired the search for targeted interventions.

ACR Appropriateness Criteria® Seizures-Child.

In children, seizures represent an extremely heterogeneous group of medical conditions ranging from benign cases, such as a simple febrile seizure, to life-threatening situations, such as status epilepticus. Underlying causes of seizures also represent a wide range of pathologies from idiopathic cases, usually genetic, to a variety of acute and chronic intracranial or systemic abnormalities. This document discusses appropriate utilization of neuroimaging tests in a child with seizures. The clinical scenarios in this document take into consideration different circumstances at the time of a child's presentation including the patient's age, precipitating event (if any), and clinical and electroencephalogram findings and include neonatal seizures, simple and complex febrile seizures, post-traumatic seizures, focal seizures, primary generalized seizures in a neurologically normal child, and generalized seizures in neurologically abnormal child. This practical approach aims to guide clinicians in clinical decision-making and to help identify efficient and appropriate imaging workup. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Quantitative electroencephalography characteristics of tilt-induced neurally-mediated syncope among youth.

OBJECTIVE: To characterize the quantitative electroencephalographic (QEEG) patterns associated with tilt-induced syncope in youth. METHODS: Several QEEG parameters were analyzed. Data were calculated for peak or nadir changes with syncope for amplitude-EEG, fast Fourier transform (FFT) power in several frequency ranges, 8-13 Hz/1-4 Hz frequency ratio, and FFT edge. RESULTS: Changes in QEEG parameters were present among all patients with tilt-induced syncope (n = 76). These changes included increases in the low frequency FFT power (1-4 Hz range), decreases in the power ratio (8-13 Hz/1-4 Hz) and decreases in the FFT edge (95%, 1-18 Hz). All patients had suppression of EEG amplitudes that closely followed loss of consciousness. Asymmetry indices demonstrated cerebral hemisphere lateralization at multiple periods during the evolution of syncope, but the side of lateralization did not differ from 0.5 probability. CONCLUSIONS: QEEG parameters can be used to characterize EEG changes associated with tilt-induced, neurally-mediated syncope. SIGNIFICANCE: QEEG may serve as a useful tool for the study of syncope neurophysiology, and the modeling of changes with syncope may improve our understanding of other neurologic disorders caused by defects in cerebral perfusion.

Language Regression in an Atypical SLC6A1 Mutation.

Recent technological advances in exome sequencing or targeted gene sequencing with epilepsy panels have allowed clinicians to better understand the pathogenesis and clinical presentation of children with epilepsy. We present a child with a SLC6A1 mutation with language delay and autistic spectrum disorder and remind the reader that the identification of specific mutations in these conditions increase the likelihood of identification of potential therapeutic targets.

Comparison of Specific Fainting Characteristics Between Youth With Tilt-Induced Psychogenic Nonsyncopal Collapse Versus Reflex Syncope.

Little is known about the predictive features of psychogenic nonsyncopal collapse (PNSC). The aim of the present study was to compare the self-reported fainting characteristics between young patients who were ultimately diagnosed with PNSC with those ultimately diagnosed with neurally mediated syncope and to determine which features were predictive of either diagnosis. A prospective study was conducted of sequential patients referred for fainting. All study data were obtained before testing or diagnosis. Several fainting characteristics were compared between cohorts including numbers of lifetime fainting episodes, fainting frequency the week before evaluation, fainting duration, numbers of fainting spells in a single day, presence of presyncope, types of prodromal symptoms, tearfulness with fainting, and the numbers of emergency department visits and hospital admission for fainting. During the study period, 52 patients were diagnosed with PNSC, producing a diagnostic rate of 18.9%. In univariate analyses, multiple features differed between patients with PNSC and those with syncope. After controlling for age and gender in a multivariate analysis, each of the following predicted PNSC: ≥20 lifetime fainting spells (p = 0.005), ≥2 fainting spells in a single day (p = 0.03), self-reported loss of consciousness ≥2 minutes (p = 0.01), and tearfulness associated with fainting (p = 0.022). Two or more typical prodromal symptoms (p = 0.004) predicted syncope. In conclusion, several characteristics related to fainting have predictive value in distinguishing PNSC from syncope, particularly among youth. Assessing these clinical features can help to inform appropriate testing and accurate diagnosis among patients who faint.

Pygopagus Conjoined Twins: A Neurophysiologic Intraoperative Monitoring Schema.

Conjoined twins occur in up to 1 in 50,000 live births with approximately 18% joined in a pygopagus configuration at the buttocks. Twins with this configuration display symptoms and carry surgical risks during separation related to the extent of their connection which can include anorectal, genitourinary, vertebral, and neural structures. Neurophysiologic intraoperative monitoring for these cases has been discussed in the literature with variable utility. The authors present a case of pygopagus twins with fused spinal cords and imperforate anus where the use of neurophysiologic intraoperative monitoring significantly impacted surgical decision-making in division of these critical structures.

Deep sedation with propofol in patients with Rett syndrome.

Herein we present the largest retrospective case-control series of deep sedation in patients with Rett syndrome, including discussion of the unique aspects of Rett syndrome that make these patients at high risk of sedation. Twenty-one patients with Rett syndrome and 21 control patients who received propofol for deep sedation to facilitate lumbar puncture were compared. Patients with Rett syndrome required significantly less propofol than control patients when standardized for weight and the duration of the procedure (P = .004). Seven of the 21 patients with Rett syndrome compared with none of the control patients experienced a serious adverse event, most of which were due to prolonged apnea (P = .004). All adverse events were transient, and all patients returned to their baseline after the procedure was completed. Sedation of patients with Rett syndrome is associated with a relatively high rate of complications and should not be done without appropriate personnel available who recognize the risks of sedating this unique population.

Deep sedation with propofol in patients with Rett syndrome.

Herein we present the largest retrospective case-control series of deep sedation in patients with Rett syndrome, including discussion of the unique aspects of Rett syndrome that make these patients at high risk for sedation. Twenty-one patients with Rett syndrome and 21 control patients who received propofol for deep sedation to facilitate lumbar puncture were compared. Patients with Rett syndrome required significantly less propofol than control patients when standardized for weight and the duration of the procedure (P = .004). Seven of the 21 patients with Rett syndrome compared with none of the control patients experienced a serious adverse event, most of which were due to prolonged apnea (P = .004). All adverse events were transient, and all patients returned to their baseline after the procedure was completed. Sedation of patients with Rett syndrome is associated with a relatively high rate of complications and should not be done without appropriate personnel available who recognize the risks of sedating this unique population.

The Clinical and Electroencephalographic Spectrum of Tilt-Induced Syncope and "Near Syncope" in Youth.

BACKGROUND: The aim of the study was to characterize the clinical and electroencephalographic (EEG) patterns associated with tilt-induced reflex syncope and delayed orthostatic hypotension without syncope in youth. METHODS: We conducted a prospective observational study of 95 patients referred to a pediatric neurology clinic for head-upright tilt testing. Clinical signs, symptoms, video EEG, and continuous blood pressure and heart rate were monitored. RESULTS: Eighty patients had reflex syncope, and 15 had delayed-onset hypotension without syncope. The mean age was 15.3 (standard deviation ±2.3) years; 75 (78.9%) were female. All patients with hypotension only had corresponding signs and symptoms; 13 (86.7%) had corresponding EEG slowing. The duration of EEG slowing with hypotension far exceeded the presyncope interval from onset of slowing to loss of consciousness among patients with syncope (P < 0.001). Although prior near-syncope and presyncope episodes were reported commonly in both groups, patients with delayed hypotension without syncope were less likely to have experienced loss of consciousness during episodes of orthostatic intolerance (P < 0.001). Patients with syncope had either slow-flat-slow (n = 23) or slow-only (n = 57) EEG patterns. Compared to those with slow-only EEG patterns, patients with the slow-flat-slow pattern had greater rates of asystole (P < 0.001), myoclonic movements (P < 0.001), facial grimace (P = 0.003), vocalizations (P = 0.002), and arm flexion (P < 0.001) or extension (P = 0.006) during tilt-induced syncope. CONCLUSIONS: Among otherwise healthy youth, orthostatic signs and symptoms vary across the spectrum of tilt-induced reflex syncope and delayed hypotension without syncope. Delayed hypotension without syncope may represent the poorly defined phenomenon of "near syncope" in some patients.

Neurocutaneous melanosis.

Neurocutaneous melanosis is a rare neurocutaneous syndrome that is associated with a high rate of mortality early in life. Individuals with large cutaneous melanocytic nevi (LCMN) are at risk, especially when the nevi are posterior, midline and accompanied by satellite nevi. Disrupted production and migration of melanocytic precursors from neural crest likely are responsible. Although the cutaneous lesions are at risk for melanoma, the most likely source of morbidity and mortality comes from "benign" melanocytic proliferation in the brain or central nervous system melanoma. Seizures and hydrocephalus are the common neurologic manifestations and typically arise in the first years of life. Brain magnetic resonance imaging in infants before myelination has matured is most sensitive for detecting abnormal melanosis in the brain, which preferentially involves the leptomeninges, cerebellum and anterior temporal lobes. Treatment is symptomatic and death occurs in many within 3 years of onset of neurologic symptoms. This prognosis may limit the extent to which extensive procedures or interventions are undertaken.

Tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a neurocutaneous syndrome that can affect the brain, skin, eyes, kidneys, heart, and lungs. TSC alters cellular proliferation and differentiation, resulting in hamartomas of various organs, tumor formation, and altered neuronal migration. The phenotype is highly variable. Most individuals have seizures, commonly including infantile spasms, and there is variable intellectual disability and autism. Neonates can present with cardiac failure due to intracardiac rhabdomyomas. The likelihood of renal angiomyolipomas increases with age, and renal disease is the most common cause of death in adults with TSC. Pulmonary involvement occurs predominantly in women and carries a high morbidity and mortality. TSC is inherited as an autosomal dominant trait, but spontaneous mutations are common. A mutation of either TSC1 on chromosome 9 or TSC2 on chromosome 16 leads to dysfunction of hamartin or tuberin, respectively. These two proteins form a functional complex that modulates the mammalian target of rapamycin (mTOR) pathway. Medications that inhibit mTOR are being used to treat TSC-related tumors, and current studies are investigating whether these agents could alleviate other TSC complications. Consensus statements guide identification and optimal management of many of the TSC-related complications at diagnosis and throughout the lifespan. A multidisciplinary approach is necessary for optimal management of individuals with TSC.

Pseudoxanthoma elasticum.

Pseudoxanthoma elasticum (PXE) is characterized by elastic tissue fragmentation and calcification. The deterioration of elastic fibers leads to characteristic yellowish papules and plaques (pseudoxanthomas) and retinal angioid streaks. Although these findings may begin in childhood, the diagnosis is typically not made until the second or third decade after the skin and retinal findings become more prominent. Cerebrovascular complications include brain infarction due to narrowing and occlusion of cerebral arteries and aneurysm formation. Intracranial hemorrhage can occur in the absence of aneurysm, and gastrointestinal hemorrhage is common. Peripheral arterial vascular disease can lead to intermittent leg claudication. A skin biopsy often demonstrates calcified elastic fibers, even in a mildly affected area of skin. The inheritance is autosomal recessive, although heterozygotes may exhibit some features of the disease. PXE is due to mutation of the ABCC6 gene on chromosome 16. There is no treatment, but certain lifestyle modifications may limit the complications. The potential for retinal hemorrhage has led to recommendations for limitations of contact sports or other activities that might facilitate eye trauma. Other recommendations include maintaining a normal lipid profile, avoidance of aspirin and nonsteroidal anti-inflammatory agents, and limiting dietary calcium intake.

Improving the inter-rater agreement of hypsarrhythmia using a simplified EEG grading scale for children with infantile spasms.

BACKGROUND: There is poor inter-rater agreement in determining the presence or absence of hypsarrhythmia among patients with infantile spasms. Yet, remission of hypsarrhythmia has been used as a clinical and research outcome measure. Two important features of hypsarrhythmia are the burden of epileptiform discharges and the amplitudes of background slow waves. We hypothesized that an electroencephalogram (EEG) grading scale emphasizing epileptiform discharge burden and the amplitudes of background slow waves would improve inter-rater agreement in interpreting hypsarrhythmia. Our aim was to assess inter-rater agreement of hypsarrhythmia using a novel and simplified EEG grading scale called the 'BASED' (Burden of Amplitudes and Epileptiform Discharges) score and compare this to the traditional method of EEG analysis. METHODS: Twenty patients with infantile spasms were prospectively evaluated and electroclinical outcomes were determined. Forty EEG clips (20 pre-treatment and 20 post-treatment), representing the most severely abnormal five minute sleep epoch of each study, were assessed by three reviewers blinded to treatment and clinical outcome. Fleiss' kappa (К) was used to assess the inter-rater agreement in the interpretation of hypsarrhythmia when using the BASED score compared to the traditional method of EEG analysis. RESULTS: Reviewers had favorable inter-rater agreement using the BASED score in interpreting hypsarrhythmia (К: 0.87) compared to when using the traditional method of EEG analysis to interpret hypsarrhythmia (К: 0.09). The three reviewers all agreed on the presence or absence of hypsarrhythmia in 37/40 (93%) epochs using the BASED score but in only 15/40 (38%) epochs using the traditional method of EEG analysis, p=<0.001. CONCLUSION: When compared to the traditional method of EEG analysis, the BASED score allowed for better inter-rater agreement in the interpretation of hypsarrhythmia. Future infantile spasms clinical trials must better define criteria for hypsarrhythmia.