Abstract 163: Discovery of Asymptomatic Moyamoya Arteriopathy in Pediatric Syndromic Populations: Radiographic and Clinical Progression

Introduction: Limited data exists to guide management of incidentally discovered pediatric moyamoya. Best exemplified in the setting of unilateral moyamoya, in which the unaffected side is monitored, this phenomenon also occurs in populations undergoing routine surveillance of the cerebral vasculature for other conditions, such as sickle cell disease (SCD) or neurofibromatosis type I (NF1). Here we present our experience with specific syndromic moyamoya populations to better characterize the natural history of radiographic and clinical progression in asymptomatic moyamoya. Methods: Retrospective review of a consecutive series of 418 patients who underwent surgical revascularization for moyamoya disease at a single institution from 1988-2010. Results: Of 418 patients, 83 were asymptomatic at the time of radiographic diagnosis of moyamoya, while also having either unilateral moyamoya or moyamoya in association with either SCD or NF1. Average age at presentation was 9.1 years (range 1-21), with 47 females (60%) and 31 males (40%). Mean follow-up was 5.4 years (SD +/-3.8), with 45 patients (54%) demonstrating radiographic progression and 37 patients (44.6%) becoming symptomatic within this period. The time interval between radiographic progression from the diagnosis of syndromic disease, to evidence of arteriopathy, to signs of slow cortical blood flow, and to stroke was 5.8 years (SD +/-4.7), 0.7 years (SD +/-1.1), and 0.3 years (SD +/-0.5), respectively. SCD patients had the highest incidence of both radiographic (n=15, 75%) and clinical (n=13, 65%) progression, followed by NF1 (n=20, 59% radiographic, n=15, 44% clinical) and unilateral patients (n=10, 34.5% radiographic, n=9, 31%). Transient ischemic attacks were the most frequent symptoms during follow-up (29 patients, 35%), and 10 patients (12%) developed clinical stroke. Overall 49 patients (59%) underwent surgical treatment, and the time between arteriopathy to surgery was 1.1 years (SD +/-1.2). Conclusion: Radiographic progression occurred in the majority of asymptomatic patients and generally heralded subsequent clinical symptoms. SCD or NF patients with asymptomatic moyamoya are more likely to progress and require treatment than unilateral moyamoya patients without a syndromic disease. These data demonstrate that moyamoya is a progressive disorder, even in asymptomatic populations, and supports the rationale of early surgical intervention to minimize morbidity from stroke.

Download Full-text

Discovery of asymptomatic moyamoya arteriopathy in pediatric syndromic populations: radiographic and clinical progression

Neurosurgical FOCUS ◽

10.3171/2011.10.focus11228 ◽

2011 ◽

Vol 31 (6) ◽

pp. E6 ◽

Cited By ~ 36

Author(s):

Ning Lin ◽

Lissa Baird ◽

McKenzie Koss ◽

Kimberly E. Kopecky ◽

Evelyne Gone ◽

...

Keyword(s):

Radiographic Progression ◽

Clinical Symptoms ◽

Neurofibromatosis Type ◽

Consecutive Series ◽

Clinical Progression ◽

Unaffected Side ◽

Asymptomatic Patients ◽

Routine Surveillance ◽

History Of ◽

The Mean

Object Limited data exist to guide management of incidentally discovered pediatric moyamoya. Best exemplified in the setting of unilateral moyamoya, in which the unaffected side is monitored, this phenomenon also occurs in populations undergoing routine surveillance of the cerebral vasculature for other conditions, such as sickle cell disease (SCD) or neurofibromatosis Type 1 (NF1). The authors present their experience with specific syndromic moyamoya populations to better characterize the natural history of radiographic and clinical progression in patients with asymptomatic moyamoya. Methods The authors performed a retrospective review of the clinical database of the neurosurgery department at Children's Hospital Boston, including both nonoperative referrals and a consecutive series of 418 patients who underwent surgical revascularization for moyamoya disease between 1988 and 2010. Results Within the period of time studied, 83 patients were asymptomatic at the time of radiographic diagnosis of moyamoya, while also having either unilateral moyamoya or moyamoya in association with either SCD or NF1. The mean age at presentation was 9.1 years (range 1–21 years), and there were 49 female (59%) and 34 male (41%) patients. The mean follow-up duration was 5.4 ± 3.8 years (mean ± SD), with 45 patients (54%) demonstrating radiographic progression and 37 (45%) becoming symptomatic within this period. Patients with SCD had the highest incidence of both radiographic (15 patients [75%]) and clinical (13 patients [65%]) progression, followed by NF1 (20 patients [59%] with radiographic progression and 15 patients [44%] with clinical progression) and patients with unilateral moyamoya (10 patients [35%] with radiographic progression and 9 patients [31%] with clinical progression). Conclusions Radiographic progression occurred in the majority of asymptomatic patients and generally heralded subsequent clinical symptoms. These data demonstrate that moyamoya is a progressive disorder, even in asymptomatic populations, and support the rationale of early surgical intervention to minimize morbidity from stroke.

Download Full-text

Recurrence of cervical artery dissection

Neurology ◽

10.1212/wnl.0000000000005324 ◽

2018 ◽

Vol 90 (16) ◽

pp. e1372-e1378 ◽

Cited By ~ 11

Author(s):

Manja Kloss ◽

Caspar Grond-Ginsbach ◽

Peter Ringleb ◽

Ingrid Hausser ◽

Werner Hacke ◽

...

Keyword(s):

Connective Tissue ◽

Recurrent Events ◽

Clinical Symptoms ◽

Artery Dissection ◽

Cervical Artery Dissection ◽

Consecutive Series ◽

Initial Event ◽

Cervical Artery ◽

Tissue Abnormalities

ObjectiveTo explore the recurrence of cervical artery dissection (CeAD).MethodsA single-center consecutive series of 282 CeAD patients was prospectively recruited during first admission from 1995 to 2012. Patients with a follow-up of at least 1 year (n = 238) were eligible for the current analysis. All patients with clinical symptoms or signs of recurrent CeAD on ultrasound were examined by MRI. Dermal connective tissue morphology was studied in 108 (45.4%) patients.ResultsMedian follow-up was 52 months (range 12–204 months). In all, 221 (92.8%) patients presented with monophasic CeAD, including 188 (79.0%) patients with a single CeAD event, 11 (4.6%) with simultaneous dissections in multiple cervical arteries, and 22 (9.2%) with subsequent events within a single phase of 4 weeks. Seventeen patients (7.1%) had late (>1 month after the initial event) recurrent CeAD events, including 5 (2.1%) with multiple recurrences. Patients with late recurrences were younger (37.5 ± 6.9 years) than those without (43.8 ± 9.9; p = 0.011). Ischemic stroke occurred in 164 (68.9%) patients at first diagnosis, but only 4 of 46 (8.7%) subsequent events caused stroke (p < 0.0001), while 19 (41.3%) were asymptomatic. Connective tissue abnormalities were found in 54 (56.3%) patients with monophasic and 8 (66.7%) with late recurrent dissections (p = 0.494).ConclusionTwenty-two (9.2%) patients had new CeAD events within 1 month and 17 (7.1%) later recurrences. The risk for new events was significantly higher (about 60-fold) during the acute phase than during later follow-up. Connective tissue abnormalities were not more frequent in patients with late recurrent events than in those with monophasic CeAD.

Download Full-text

Glutaric Aciduria Type I

10.1093/med/9780199972135.003.0021 ◽

2016 ◽

Author(s):

Stefan Kölker

Keyword(s):

Clinical Symptoms ◽

Neurological Complications ◽

Glutaric Aciduria Type ◽

Organic Aciduria ◽

Type I ◽

Hand Tremor ◽

Glutaric Aciduria ◽

Glutaric Aciduria Type I ◽

Asymptomatic Patients ◽

Cranial Mri

Glutaric aciduria type I is a rare organic aciduria caused by inherited deficiency of glutaryl-CoA dehydrogenase, a mitochondrial enzyme involved in the final common catabolic pathways of L-lysine, L-hydroxylysine, and L-trytophan. The majority of untreated patients develop striatal injury and secondary dystonia during infancy and childhood, whereas identification by newborn screening and immediate start of metabolic treatment (low-lysine diet, carnitine supplementation, metabolic emergency treatment) helps to prevent severe neurological complications in the majority of patients. The morbidity and mortality of dystonic patients is high, whereas asymptomatic patients have normal life expectancy. Effective antidystonic treatment requires a multidisciplinary approach. In a subgroup of patients, first clinical symptoms (headaches, vertigo, gait disturbance, hand tremor) may not manifest before adulthood. Cranial MRI studies in these patients reveal T2 hyperintensities of supratentorial white matter. A few women with glutaric aciduria type I have had unremarkable pregnancies, deliveries, and postpartal periods.

Download Full-text

Fatal glioblastoma multiforme in a patient with neurofibromatosis type I: the dilemma of systematic medical follow-up

Child s Nervous System ◽

10.1007/s00381-006-0222-4 ◽

2006 ◽

Vol 23 (3) ◽

pp. 343-347 ◽

Cited By ~ 9

Author(s):

Felix Distelmaier ◽

Raimund Fahsold ◽

Guido Reifenberger ◽

Martina Messing-Juenger ◽

Jörg Schaper ◽

...

Keyword(s):

Glioblastoma Multiforme ◽

Neurofibromatosis Type ◽

Type I ◽

Neurofibromatosis Type I

Download Full-text

564 Controversial role of intracardiac eletrophysiology study in Brugada syndrome: analysis of a single-centre retrospective cohort study

European Heart Journal Supplements ◽

10.1093/eurheartj/suab127.014 ◽

2021 ◽

Vol 23 (Supplement_G) ◽

Author(s):

Claudio Licciardello ◽

Jacopo Marazzato ◽

Michele Golino ◽

Francesca Seganfreddo ◽

Federica Matteo ◽

...

Keyword(s):

High Risk ◽

Risk Stratification ◽

Right Ventricular ◽

Brugada Syndrome ◽

Type I ◽

Drug Induced ◽

Programmed Ventricular Stimulation ◽

Asymptomatic Patients ◽

Ventricular Stimulation

Abstract Aims According to European guidelines, aborted sudden cardiac death (SCD) in Brugada syndrome (BrS) is regarded as a I class recommendation for secondary prevention implantable cardioverter defibrillator (ICD). However, the risk stratification of BrS patients for primary prevention ICD still represents a clinical conundrum. Although intracardiac electrophysiology (EP) study proved useful for the selection of high-risk patients in this setting. Therefore, aim of this study was to assess all clinical and EP variables associated with the induction of VA at EP study and the rate of appropriate/inappropriate ICD interventions and/or clinical SCD events in these patients occurring at follow-up. Methods and results From 2001 to 2021, all EP studies performed in symptomatic/asymptomatic patients (46 ± 14 years, M 88%) with/without family history of SCD spontaneous/drug-induced type I pattern (TIP) on ECG and no spontaneous ventricular arrhythmias were retrospectively considered at our study centre. Clinical variables, BrS pattern, EP study data (including right ventricular site and type of stimulation protocol), and ICD interventions (DC-shocks or Anti-Tachycardia Pacing events, ATP) and/or SCD events occurring at follow-up were all evaluated. EP study was deemed positive for any polymorphic VA induced during programmed ventricular stimulation; non-sustained episodes included. ICD was routinely implanted in all patients with a positive EP study. Follow-up data were detected by the collection of medical and home-monitoring recordings at study-site level. Follow-up data were available in 50 patients (9 ± 6 years on average). Patients were generally young with few cardiovascular comorbidities. SCD history was known in 21 (42%) with a significant number of asymptomatic patients (48%). Br patterns were equally distributed in the investigated population (spontaneous and drug-induced TIP in 52% and 48%, respectively) and AF history was fairly common (16%). In the study population, EP study tested positive in 30 patients (60%): spontaneous TIP (P = 0.0518), few extrastimuli during programmed ventricular stimulation (P = 0.0015), and right ventricular stimulation at the apical site (P ≤ 0.0001) were the only variables to be clearly associated with a positive EP study in the appraised patients. At follow-up, appropriate ICD shocks were documented in 4 out of 30 implanted patients (13%) at generally 5 ± 7 years from EP study evaluation. Although three ICD interventions (75%) occurred in patients with spontaneous TIP, one patient with drug-induced TIP pattern and positive EP study referred to Emergency Department for unrelenting VT storm after roughly 13 years from ICD implantation. Inappropriate ICD interventions for fast rate AF were detected in 10% of cases. Finally, no SCD events were documented at follow up in patients with a negative EP study. Conclusions In a retrospective analysis, EP study proved useful in the risk stratification of SCD in BrS patients. A few ventricular extrastimuli delivered at the right ventricular apex seem sufficient to prompt the induction of life-threatening VA in high-risk BrS patients during EP study. Moreover, in this setting, a negative EP study seems protective against the development of VA/SCD events at follow-up. However, not only is spontaneous TIP associated with an increased risk of arrhythmic death, but a drug-induced TIP, generally regarded as a low-risk condition, might also be associated with a long-term hazard of SCD in these patients.

Download Full-text

P506Brugada Syndrome: is the addition of the electrocardiographic risk markers the clue?

EP Europace ◽

10.1093/europace/euaa162.144 ◽

2020 ◽

Vol 22 (Supplement_1) ◽

Author(s):

A Tronconi ◽

G Carnero ◽

M Mysuta ◽

A Bozza ◽

M Peltzer ◽

...

Keyword(s):

Risk Stratification ◽

Electrophysiological Study ◽

First Grade ◽

Time Interval ◽

Risk Marker ◽

Risk Markers ◽

T Wave ◽

Asymptomatic Patients ◽

Significant Difference

Abstract Background Risk stratification in Brugada Syndrome (BS) remains a clinical challenge. Several electrocardiografic (ECG) risk markers had been described, as a spontaneous type 1 Brugada pattern (ST1B), maximal time interval between the peak and the end of the t wave in precordial leads (Tpe Max), the presence of an S Wave on DI, a PR interval (PRi) ≥ 200ms and fragmented QRS (f-QRS). Purpose Evaluate the association of ECG risk markers with sudden cardiac death (SCD) or appropriate shocks (A-Sh) by implantable cardioverter defibrillator (ICD) in patients (p) with BS. Methods From a registry of 97 p with BS with a median follow up of 2.3 years (Q1 0.7-Q3 7.8), 12 lead ECG were recorded in every p. QT peak interval (QTp) was measured between the QRS onset and the peak of the T wave. Tpe was calculated between the difference of QT and QTp in precordial leads (V1 to V6). TpeMax was defined as the most prolonged Tpe. If an S-DI was present, duration and amplitude was measured. PRi was measured on DII. Baseline characteristics: Age 44 ± 13 years, male 74 (76%), secondary prevention 2 (3%), malignant syncope 10 (10%), inducible electrophysiology study 22/43 (51%), SCD on first grade family < 35 years 12 (12%) and ICD 34 (35%). A-Sh and SCD were compared among p with ST1B vs no ST1B, TpeMax≥100 vs <100ms, S-DI ≥0.4 vs <0.4ms, S-D ≥0.1 vs <0.1mV, PRi≥200 vs <200ms and presence of f-QRS ≥ 2 spike ≥ 2 leads. Variables that were associated with A-Sh or SCD were combined. For variables with significant difference sensibility (Sen) and specificity (Spe) was calculated. Results During follow up 6 p presented A-Sh and no p SCD. Results are described in the Table. Conclusion In our study population, there was a significant higher incidence of A-Sh in p with ST1B, Tpe Max ≥ 100ms and S-DI ≥ 0.1mV. We found that the presence of one ECG risk marker had a high sensibility to predict A-Sh. The presence of the 3 ECG risk markers highly increased specificity to predict A-Sh. Further trials should be carried out to asses if ECG risk markers would allow us to differentiate which asymptomatic patients could benefit from electrophysiological study for risk stratification (high sensibility - One ECG Risk marker) or would benefit from ICD implantation (high specificity - 3 ECG Risk markers). Abstract Figure.

Download Full-text

Gastrointestinal stromal tumor associated with neurofibromatosis type I.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.10539 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 10539-10539

Author(s):

Toshirou Nishida ◽

Tsuyoshi Takahashi ◽

Mari Kaneda ◽

Maiko Ako ◽

Takeshi Omori ◽

...

Keyword(s):

Neurofibromatosis Type ◽

Type I ◽

Short Term ◽

Distinctive Features ◽

Increased Risk ◽

Nf1 Gene ◽

Normal Intestine ◽

Single Lesion

10539 Background: Most gastrointestinal stromal tumors (GIST) have either KIT or PDGFRA mutations. Neurofibromatosis type 1 pts caused by mutations in the NF1 gene have increased risk of GIST development, which may have no mutation in both genes. In this study, we analyzed clinical and pathological features of NF-1 associated GISTs. Methods: Study 1: We have screened 95 adults NF1 pts (age 31-66, 35 male and 60 female) by enhanced MDCT between 2003 and 2012. Study 2: We collected 1,184 sporadic GISTs from community hospitals in Japan between 2001 and 2010 retrospectively, and found 24 primary NF1-GISTs (1.7% of sporadic) and 2 recurrent NF1-GISTs, of whom clinicopathological features were analyzed. Results: Study1: By MDCT screening, we have found histologically confirmed 6 GISTs (4 males and 2 female; 6/1,000 NF1-persons/year) in the small intestine. Median age of NF1-GIST was 45, and five pts had multiple tumors, ICC hyperplasia in the normal intestine and no mutation in the KIT and PDGFRA genes. Study 2: Median age of 26 NF1-GIST (12 male and 14 female) was 58. 25 GISTs were located in the small bowel and one in the stomach. 17 pts had multiple GISTs and 9 pts single lesion. Pathologically, KIT was positive for all NF1-GISTs. 24 pts had spindle cell tumors and 2 had mixed or epithelioid. No mutation was found in the KIT and PDGFRA genes of 11 pts examined. Median values of mitosis (0/50HPF) and Ki67 (0.5%) were lower than those of sporadic GIST (3/50HPF and 2.5%). With media follow-up of 3.6 years, 8 pts had recurrences and 4 pts died of the disease. By western blotting, KIT was faintly phosphorylated but its downstream kinases including MEK, p44/22, AKT, mTOR, p38 and STAT3, were activated. Six pts received imatinib and had no response and, subsequently, 5 pts received sunitinib with 4 PD and 1 short-term SD. Conclusions: NF1-associated GIST is a rare entity of GIST and has distinctive features from conventional sporadic GISTs. KIT-targeted TKI appeared to be ineffective to recurrent and advanced NF1-GISTs.

Download Full-text

Are Follow-up X-rays Necessary

PEDIATRICS ◽

10.1542/peds.64.1.123b ◽

1979 ◽

Vol 64 (1) ◽

pp. 123-124

Author(s):

Wilbur L. Smith

Keyword(s):

Data Base ◽

Clinical Improvement ◽

Pediatric Patient ◽

Clinical Symptoms ◽

Time Interval ◽

X Rays ◽

Significant Time ◽

Interesting Study ◽

Acute Pneumonia

Grossman, Wald, Nair, and Papiez have reported an interesting study on roentgenographic follow-up of acute pneumonia (Pediatrics 63:30, 1979). Their data suggest that routine follow-up radiographs are not reliably normal until six weeks to three months after initial diagnosis despite the patient's clinical improvement. Their emphasis on not radiographing a clinically well pediatric patient until a significant time interval after onset of disease is certainly reasonable. From this data base they go on, however, to recommend that routine follow-up radiographs in pneumonia patients are only needed if clinical symptoms persist.

Download Full-text

Management of incidental pituitary tumors

Oncology Reviews ◽

10.4081/oncol.2011.232 ◽

2011 ◽

Vol 5 (4) ◽

pp. 232

Author(s):

Nicholas F. Marko ◽

Robert J. Weil

Keyword(s):

Clinical Symptoms ◽

Visual Fields ◽

Pituitary Tumors ◽

Field Testing ◽

Serum Levels ◽

Thyroid Stimulating Hormone ◽

Mri Imaging ◽

Asymptomatic Patients ◽

Stimulating Hormone

Pituitary incidentalomas are common lesions for which neurosurgical referrals may become progressively more frequent, given the increasing application of neuroimaging. The initial evaluation of a patient with radiographic evidence of an incidentaloma should focus on addressing two questions: (1) is the lesion causing neurological symptoms, and (2) is the lesion hormonally active? The answers to these two questions provide a framework for subsequent clinical management. The initial patient assessment should include a detailed history and physical examination, including the bedside assessment of visual fields. High-quality MRI imaging is essential, and formal visual field testing should be obtained in patients where the lesion abuts or compresses the optic apparatus. The initial biochemical workup is intended to assess potential pituitary hypo- or hyperfunction and should include measurement of serum levels of prolactin, insulin-like growth factor type-1, free thyroxine, testosterone, and an assessment of axis hypothalamic–pituitary–adrenal axis function. Additional testing may include serum thyroid-stimulating hormone, follicle-stimulating hormone, and luteinizing hormone levels. Neurologically-asymptomatic patients without endocrine dysfunction can be managed with observation at regular intervals, including MRI imaging at 6 months and 1 year and then annually for a period of 3 years. Follow-up biochemical assessment is not necessary in the absence of clinical symptoms or radiographic enlargement of the lesion. After 3 years the follow-up interval may be prolonged, although closer follow-up may be indicated for patients with lesions C1 cm. Most patients who either present with or who subsequently develop neurologic or endocrinologic symptoms should be considered for surgery as the first-line therapy.

Download Full-text

Syringomyelia intermittens: highlighting the complex pathophysiology of syringomyelia. Illustrative case

Journal of Neurosurgery: Case Lessons ◽

10.3171/case21341 ◽

2021 ◽

Vol 2 (11) ◽

Author(s):

Jorn Van Der Veken ◽

Marguerite Harding ◽

Saba Hatami ◽

Marc Agzarian ◽

Nick Vrodos

Keyword(s):

Clinical Symptoms ◽

Incidental Finding ◽

Foramen Magnum ◽

Illustrative Case ◽

Cervical Canal ◽

Type I ◽

Natural Evolution ◽

Chiari Type I Malformation ◽

Asymptomatic Patients ◽

History Of

BACKGROUND Chiari Type I malformation (CM1) is a disorder recognized by caudal displacement of the cerebellar tonsils through the foramen magnum and into the cervical canal. Syringomyelia is frequently found in patients with CM1, but the pathophysiology of syringomyelia remains an enigma. As a general consensus, symptomatic patients should be treated and asymptomatic patients without a syrinx should not be treated. Mildly symptomatic patients or asymptomatic patients with a syrinx, on the other hand, pose a more challenging dilemma, as the natural evolution is uncertain. For many surgeons, the presence of a syrinx is an indication to offer surgery even if the patient is asymptomatic or mildly symptomatic. OBSERVATIONS The authors describe an illustrative case of a 31-year-old female with an incidental finding of a CM1 malformation and cervical syrinx in 2013. Conservative management was advocated as the patient was asymptomatic. Monitoring of the syrinx over a course of 8 years showed resolution, followed by reappearance and finally a complete resolution in 2021. A review of the literature and the possible pathophysiology is discussed. LESSONS The unusual course of this patient highlights the importance of guiding treatment by clinical symptoms, not radiological findings. Furthermore it reflects the complexity of the pathophysiology and the uncertain natural history of syringomyelia.

Download Full-text