Migraine Disorders: Li BU

Li BU. · No affiliation provided · Pediatr Ann. · Pubmed #19476294 No free full text.

Abstract: From the array of articles, one can readily see the clinical and scientific progress made in symptom-based diagnosis and management of functional abdominal pain disorders over the past 5 years. We have provided a series of useful tools to approach these patients. We have provided the symptom-based diagnostic criteria plus the red flags to help you avoid missing an organic diagnosis. We have placed these disorders squarely within the complex biopsychosocial framework by identifying early life stress and many environmental factors that are key factors in the development of pain. We have identified the role of psychological comorbidities of anxiety and depression and the need to address them directly in order to rehabilitate a disabled child. Finally, pharmacologic, psychological, dietary, and complementary approaches are reviewed and recommended as empiric therapy in functional abdominal pain, functional dyspepsia, and irritable bowel syndrome. Use these new tools well.

Li BU. · No affiliation provided · J Pediatr. · Pubmed #10484788 No free full text.

This publication has no abstract.

Li BU, Misiewicz L. · Department of Pediatrics, Feinberg School of Medicine, Northwestern University and Children's Memorial Hospital Chicago, IL 60614, USA. · Gastroenterol Clin North Am. · Pubmed #14562585 No free full text.

Abstract: Despite the "black box" surrounding CVS, the authors' understanding of this clinical entity has advanced substantially in the last decade as a result of an international interdisciplinary clinical and research effort. Although CVS is now recognized as a unique clinical entity, patients still undergo innumerable hospitalizations and diagnostic tests. Although controlled therapeutic studies are lacking, reasonably effective empiric approaches have been developed by trial and error using anti-migraine, anti-emetic, and anti-epileptic regimens. The ongoing investigations of migraine mechanisms through NMR spectroscopy, mitochondrial DNA mutations and cellular energetics, corticotropin-releasing factor and gastric motility, and brainstem regulation of autonomic function may lead to breakthroughs in the understanding of and new therapies for CVS in the next decade.

Li BU. · Department of Pediatrics, Northwestern University, and Children's Memorial Hospital, Chicago, IL 60614-3394, USA. · Semin Pediatr Neurol. · Pubmed #11332860 No free full text.

Abstract: Cyclic vomiting is a variant of migraine that is discussed in depth. The importance of the diagnostic criteria, differential diagnosis, supportive and pharmacologic therapies is stressed.

Li BU, Balint JP. · Ohio State University, USA. · Adv Pediatr. · Pubmed #10959442 No free full text.

Abstract: Cyclic vomiting syndrome (CVS) remains a mysterious disorder despite our increasing knowledge since its classic description by Gee in 1882. Its hallmark feature of recurrent, explosive bouts of vomiting punctuating periods of normal health causes substantial medical morbidity (50% of patients require intravenous therapy), as well as significant time lost from school (20 school absences per year) and work. Limited epidemiologic data indicate that CVS may occur more commonly than previously thought, affecting as many as 1.9% of school-aged children. Besides the relentless vomiting, the child usually has pallor (87%), lethargy (91%), anorexia (74%), nausea (72%), and abdominal pain (80%). There is evidence of clinical and physiologic overlap among CVS, abdominal migraine, and migraine headaches. We propose revised criteria for abdominal migraine that include pain as the predominant and consistent symptom, lack of abnormal screening tests, and in retrospect, either subsequent development of migraines or positive response to antimigraine medication. Besides migraines, other etiologic possibilities include mitochondrial DNA mutations, ion channelopathies, excessive hypothalamic-pituitary-adrenal axis activation, and heightened autonomic reactivity. The differential diagnosis includes idiopathic CVS (88%); gastrointestinal disorders (7%), including serious surgical disorders (e.g., malrotation); and extraintestinal disorders (5%), including serious surgical (brain stem neoplasm) and metabolic disorders (e.g., fatty acid oxidation disorder). Within the idiopathic group, there may be migraine, Sato's neuroendocrine, mitochondrial, and other subgroups. Treatment includes avoidance of triggers, prophylactic medication, supportive care, abortive medication, and family support. In the future, investigation into mitochondrial DNA mutations, ion channel defects, corticotropin-releasing factor, and serotonin and tachykinin receptor physiology and pharmacology may help discover the etiology and pathogenesis of this disorder.

Li BU, Fleisher DR. · Department of Pediatrics, The Ohio State University, Columbus, USA. · Dig Dis Sci. · Pubmed #10490033 No free full text.

Abstract: Cyclic vomiting syndrome is a disorder of unknown etiology that is characterized by its clinical pattern of rapid-fire, episodic (on-off) vomiting with interval wellness. The pattern is stereotypic within individuals and typified by a rapid onset during the night or early morning, rapid denouement, and associated symptoms of pallor, lethargy, anorexia, nausea, retching, vomiting, and abdominal pain. The vomiting appears to be triggered by a variety of physical and psychological stresses. The disorder usually begins in toddlers and resolves during adolescence. By definition, cyclic vomiting syndrome is an idiopathic disorder that requires exclusionary laboratory testing. Not only can it be mimicked by many specific disorders, eg, surgical, neurologic, endocrine, metabolic, renal, but within idiopathic cyclic vomiting syndrome there may be specific subgroups that have different mechanisms. Treatment options are improving at present and serotonergic agents have the most promise. Although the pathogenesis is unknown, there are now several tenable mechanisms including migraine, metabolic, neuroendocrine, and gastrointestinal. Cyclic vomiting syndrome may be a useful model for the study of emesis.

Boles RG, Adams K, Li BU. · Division of Medical Genetics and the Saban Research Institute, Childrens Hospital Los Angeles, Los Angeles, California, USA. · Am J Med Genet A. · Pubmed #15643622 No free full text.

Abstract: Cyclic vomiting syndrome (CVS), characterized by severe discrete episodes of nausea, vomiting, and lethargy, is a fairly common, disabling, predominately-childhood condition most often associated with migraine and dysautonomic features. Our group recently reported that children with CVS and additional neuromuscular disease manifestations demonstrate strong maternal inheritance of multiple disease manifestations and abnormal urine organic acids, suggesting the presence of predisposing mitochondrial DNA (mtDNA) sequence variants. In order to determine if maternal inheritance is present in CVS in general, a clinical interview was administered regarding 80 unrelated individuals with CVS ascertained randomly from the database of the Cyclic Vomiting Syndrome Association (CVSA). Disease manifestations consistent with potential mitochondrial dysfunction were far more common in matrilineal (sharing the same mtDNA sequence) versus in non-matrilineal relatives, including mothers versus fathers (P = 3 x 10(-9)) and maternal versus paternal grandmothers (P = 2 x 10(-6)). Maternal inheritance is suggested in 52% of the 23 subjects with two or more neuromuscular abnormalities ("CVS+") and in 54% of the 44 subjects without any neuromuscular abnormalities ("CVS-"). In both the CVS+ and CVS- sub-groups, subjects, and affected matrilineal relatives of all ages suffer at a far higher incidence from several dysautonomic-related conditions, including migraine and irritable bowel, as well as depression and hypothyroidism, while neuromuscular and cognitive disorders such as hypotonia and ADHD are common only in affected children. We conclude that mtDNA sequences predispose towards the development of protean disease manifestations in CVS patients ascertained through a disease-specific association, as well as among their matrilineal relatives, whether or not neuromuscular disease is present in the proband. Since CVS was absent in all but one matrilineal relative of our probands, CVS is apparently a rare clinical presentation in individuals carrying the predisposing mtDNA sequences. The four conditions reported most frequently among the matrilineal relatives of our cases, migraine, depression, irritable bowel, and hypothyroidism, are known to segregate together in families, and our findings suggest that a common predisposing genetic factor is likely present on the mtDNA.

Wang Q, Ito M, Adams K, Li BU, Klopstock T, Maslim A, Higashimoto T, Herzog J, Boles RG. · Division of Medical Genetics, Childrens Hospital Los Angeles, California, USA. · Am J Med Genet A. · Pubmed #15368478 No free full text.

Abstract: Migraine headache is a very common condition affecting about 10% of the population that results in substantial morbidity and economic loss. The two most common variants are migraine with (MA) and without (MO) aura. Often considered to be a migraine-like variant, cyclic vomiting syndrome (CVS) is a predominately childhood condition characterized by severe, discrete episodes of nausea, vomiting, and lethargy. Disease-associated mitochondrial DNA (mtDNA) sequence variants are suggested in common migraine and CVS based upon a strong bias towards the maternal inheritance of disease, and several other factors. Temporal temperature gradient gel electrophoresis (TTGE) followed by cyclosequencing and RFLP was used to screen almost 90% of the mtDNA, including the control region (CR), for heteroplasmy in 62 children with CVS and neuromuscular disease (CVS+) and in 95 control subjects. One or two rare mtDNA-CR heteroplasmic sequence variants were found in six CVS+ and in zero control subjects (P = 0.003). These variants comprised 6 point and 2 length variants in hypervariable regions 1 and 2 (HV1 and HV2, both part of the mtDNA-CR), one half of which were clustered in the nt 16040-16188 segment of HV1 that includes the termination associated sequence (TAS), a functional location important in the regulation of mtDNA replication. Based upon our findings, sequencing and statistical analysis looking for homoplasmic nucleotide changes was performed in HV1 among 30 CVS+, 30 randomly-ascertained CVS (rCVS), 18 MA, 32 MO, and 35 control haplogroup H cases. Within the nt 16040-16188 segment, homoplasmic sequence variants were three-fold more common relative to control subjects in both CVS groups (P = 0.01 combined data) and in MO (P = 0.02), but not in MA (P = 0.5 vs. control subjects and 0.02 vs. MO). No group differences were noted in the remainder of HV1. We conclude that sequence variation in this small "peri-TAS" segment is associated with CVS and MO, but not MA. These variants likely constitute risk factors for disease development. Our findings are consistent with previous data demonstrating progression of CVS into MO in many cases, and the co-segregation in a maternal inheritance pattern of CVS and MO within families. A mitochondrial component in the pathogenesis of migraine and CVS has therapeutic implications, especially concerning the avoidance of fasting.

Boles RG, Adams K, Ito M, Li BU. · Division of Medical Genetics, Childrens Hospital Los Angeles, Los Angeles, California 90027, USA. · Am J Med Genet A. · Pubmed #12884425 No free full text.

Abstract: Cyclic vomiting syndrome (CVS), characterized by severe discrete episodes of nausea, vomiting, and lethargy, is a predominately childhood condition associated with migraine and dysautonomic features. Disease-associated mitochondrial DNA (mtDNA) sequence variants are suggested by a strong maternal bias in the inheritance of migraine, and the recent findings of mtDNA variants in a few children with CVS and additional neuromuscular disease manifestations ("CVS+"). A clinical interview using a questionnaire was administered (generally) to one parent of 62 children with CVS+. Non-senile disease manifestations, including migraine, myopathy, seizures, and dysautonomia-like symptoms, were far more common in matrilineal versus non-matrilineal relatives, including being present in 75% of the mothers versus in only 11% of the fathers (P < 0.001). Overall, maternal inheritance is suggested in 86% of the families (in 65% strongly so). Disease manifestations in subjects and their affected matrilineal relatives are predominately intermittent and consistent with dysautonomia, including increased vital sign fluctuations. Body fluid metabolites and muscle biopsy findings are consistent with mitochondrial dysfunction in most cases tested. We conclude that mtDNA sequence variants are at least risk factors in the development of disease in most children at this "severe" end of the CVS spectrum, likely involving a maternally inherited propensity towards dysautonomia.

Olson AD, Li BU. · C. S. Mott Children's Hospital and the University of Michigan, Ann Arbor, Michigan, USA. · J Pediatr. · Pubmed #12410206 No free full text.

Abstract: Because patients with cyclic vomiting often (82%) have a family history of migraines and often (60%) respond to antimigraine therapy, we investigated whether an initial therapeutic trial could precede diagnostic testing. We used a decision analysis program to compare the cost and benefit of three initial treatment strategies. The costs of the three strategies were extensive diagnostic evaluation, $3020; empiric treatment alone, $1830, and upper GI series with small-bowel follow-through (UGI-SBFT) plus empiric treatment, $1600, respectively. When compared with the extensive evaluation strategy, initial antimigraine treatment avoided 65% of the esophagogastroduodenoscopys. On the basis of this decision analysis, a UGI-SBFT plus empiric migraine therapy was the most cost-effective initial strategy to treat cyclic vomiting syndrome. The cost of complications of a missed malrotation with volvulus was higher than that of adding a UGI-SBFT to each evaluation.

Li BU, Murray RD, Heitlinger LA, Robbins JL, Hayes JR. · Department of Pediatrics, The Ohio State University, Columbus Children's Hospital, Columbus, Ohio, USA. · J Pediatr. · Pubmed #10228291 No free full text.

Abstract: OBJECTIVE: To examine the overlap between cyclic vomiting syndrome (CVS) and migraine by comparing 2 subsets of children with migraine-associated and non-migraine-associated CVS. METHODS: We studied all children <18 years of age who met the consensus criteria for CVS after presentation to our pediatric gastroenterology service from 1986 to 1998. The clinical patterns and responses to treatment were obtained from a combination of chart reviews and structured interviews. RESULTS: Among 214 children identified as having CVS, 82% were classified as having migraine-associated CVS based on 1 of 2 criteria either a family history of migraines or subsequent development of migraine headaches. Compared with the non-migraine CVS subgroup, the migraine subset had milder episodes (20.7 27.3 SD vs 39.5 66.5 emeses/episode, P =.006); more symptoms of abdominal pain (83% vs 66%), headache (41% vs 24%), social withdrawal (40% vs 22%), photophobia (36% vs 16%, all P <.05); more frequent triggering events (70% vs 49%, P =.013) including psychologic stress (39% vs 22%), physical exhaustion (23% vs 3%), and motion sickness (10% vs 0%); and a higher positive response rate to anti-migraine therapy (79% vs 36%, P =.002). CONCLUSIONS: The majority of children with CVS were subclassified as having migraine-associated CVS. The migraine-associated subgroup had less severe vomiting, manifested symptoms typical of migraine headaches, and had higher response rates to anti-migraine therapy. These findings strengthen the relationship between migraine and CVS.