842 SECTION VI Pediatric Critical Care Neurologic was found to partially block the activity of d aminolevulinic acid synthetase The treated patients were found to have a reduced number of attacks and[.]
842 S E C T I O N V I Pediatric Critical Care: Neurologic was found to partially block the activity of d-aminolevulinic acid synthetase The treated patients were found to have a reduced number of attacks and the levels of d-aminolevulinic acid and porphobilinogen nearly normalized.110 Diagnostically, urine and stool can be tested for a-aminolevulinic acid (ALA) Also, there is a marked elevation of urinary porphobilinogen (PBG) In the blood, PBG deaminase is helpful in that its level is abnormal even between the acute attacks.107 AIP should be a consideration in the differential diagnosis of progressive weakness It is most often confused with GBS The ascending weakness that is classic in GBS is rare in acute porphyria Additionally, acute porphyria does not have elevation of CSF protein or leukocytosis The associated abdominal discomfort and tachycardia that are seen in porphyria would not be anticipated in GBS Differential considerations should also include lead intoxication and hereditary tyrosinemia Elder and Hift107 provide a review of AIP therapy The two recommended approaches are carbohydrate loading and administration of heme to replenish the depleted heme that is the principal product of porphyrin metabolism If the patient has severe symptoms—such as seizures, hyponatremia, and initial signs of neuropathy—aggressive therapy should begin as early in the crisis as possible.109 In mild attacks, it may be possible to wait 24 hours to determine whether the attack will resolve spontaneously Carbohydrate loading is delivered as a 20% glucose solution provided via a central venous catheter Studies that support the use of heme are primarily noncontrolled and have difficulty reaching statistical significance, but the overall consensus is that it does provide benefit Daily measurements of urinary ALA or PBG may be a helpful clinical monitor Spinal Muscular Atrophy Spinal muscular atrophy (SMA), a disease of the anterior horn cell, is most commonly inherited in an autosomal recessive manner The responsible gene is the survivor motor neuron gene on chromosome 5q13.111,112 SMA has three subtypes that present in childhood; both autosomal-dominant and X-linked inheritance have been reported The combined incidence of all forms of SMA has been estimated as case in 6000 to 25,700 live births.113,114 After cystic fibrosis, SMA is the next most common fatal disease with an autosomal recessive pattern of inheritance.109 The most severe form was previously known as Werdnig-Hoffmann disease but is now more commonly referred to as SMA type I It classically presents shortly after birth The findings should be apparent before age months; type I SMA is often clinically defined by the inability for the patient to achieve independent sitting SMA type II usually presents between ages and 18 months and is characterized by the patient sitting but never standing or walking In SMA type III, patients stand independently and walk In patients with SMA type I, the examination reveals a floppy baby with proximal weakness greater than distal The lower extremities are more affected than the upper extremities, and the only spontaneous movement in these infants may be in the hands and feet When supine, the infant will assume a frog-legged position Polyminimyoclonus, a fine tremor most easily visualized in the hands, may also be present in these patients Areflexia, tongue fasciculations, facial weakness, and normal sensation are also found.115,116 Retrospectively, some mothers will report decreased fetal movement during the pregnancy with the affected infant Death often occurs before years of age as a result of respiratory failure.113 Patients with clinical symptoms within the first day of life have a life expectancy between and months, with a mean age at death slightly before months.117 Patients with SMA type II usually have delayed motor milestones after having normal motor development in infancy Polyminimyoclonus is also present in these patients Life expectancy is variable, with many patients not surviving past adolescence.113 Life expectancy can be enhanced, however, with fastidious respiratory care.118 Not surprising was the correlation that patients with an earlier onset of the disease had an earlier death.119 In SMA type III, weakness is again more proximal than distal, with the lower extremities being more severely affected The gait exhibited in these patients has a waddling quality, and lumbar lordosis is also prominent.120 If symptoms begin after age years, ambulation may continue to a median age of 44 years.120 If symptoms begin before age years, ambulation continues to a median age of 12 years.120 Life expectancy for patients with SMA type III may be the same as in the normal population because muscle weakness appears to stabilize in these patients Electrodiagnostic studies on these patients reveal normal motor conduction velocities Over time, the amplitude of the compound muscle action potential may be decreased Results from sensory nerve conduction studies are normal EMG reveals evidence of acute denervation with spontaneous activity and chronic denervative changes with polyphasic motor units Muscle biopsy specimens reveal angulated fibers suggestive of denervation The creatine phosphokinase (CPK) level may or may not be increased Genetic testing is used to confirm the diagnosis Respiratory complications are the most concerning aspect of this disease, which include aspiration, pneumonia, and respiratory failure Respiratory failure may even be the presenting symptom in SMA type I.121 Respiratory muscle weakness results in restrictive lung disease with a weak cough and hypoventilation.116 Hypercapnia is also a consequence of restrictive lung disease—as a result, isolated supplemental oxygen may have devastating consequences, including apnea and death.116 If supplemental oxygen is needed, conventional ventilation or noninvasive ventilation should be instituted Other complications may also occur over time including scoliosis and contractures Scoliosis also complicates pulmonary function over time because of chest wall alterations In addition, feeding difficulties play a prominent role, particularly in the developing infant with SMA type I If concerns arise, feeding evaluation should be performed to rule out aspiration Supplemental feeding through nasogastric tube or gastrostomy may be necessary.119 Aggressive symptomatic treatment, including more frequent use of ventilation and gastrostomy, has been associated with longer lifespans Multiple pharmacologic treatments have not been successful.122 However, more recent developments have occurred in the treatment of patients with SMA Nusinersen is the first drug approved by the US Food and Drug Administration (December 2016) to treat children and adults with SMA.123 Nusinersen, an antisense oligonucleotide that increases production of survival motor neuron (SMN) protein by modification of the SMN2 gene, is administered intrathecally, initially as loading doses given in frequent intervals followed by maintenance dosing every months Nusinersen versus sham control studies in both infantile-onset and later-onset SMA have demonstrated improvements in motor function when compared with control groups.124,125 Another treatment that is on the horizon is an IV administered adeno-associated virus carrying the missing SMN copy that promotes SMN production.126 AVXS10 is given IV as a single dose and has been shown to result in longer survival and greater motor function than in historical cohorts in patients with SMA type I CHAPTER 68 Acute Neuromuscular Disease and Disorders Poliomyelitis The paralytic form of polio represents only 1% to 2% of the actual infections Aseptic meningitis represents less than 10% and is often thought to be a nonspecific illness; the remainder of those affected have no apparent infection Patients with the paralytic disorder present with very high fevers, significant muscle pain, and lack of reflexes Paralysis rapidly progresses over a few hours to a complete asymmetric loss of motor use in one or more extremities Classically, the weakness peaks at days The distribution of weakness is predominantly proximal and in the lower extremities, with cranial nerve abnormalities reported in 5% to 35% of the patients Bowel and bladder problems may occur over the initial days Sensory abnormalities are rare Classically, the “head drop” may occur on examination: as the examiner lifts the patient’s shoulders and raises the trunk from supine, the head falls backward in a limp fashion It is thought that this is not due to paralysis of the neck muscles because it can occur in the nonparalytic form The clinical course may include significant respiratory muscle weakness Involvement of the bulbar muscles, brainstem, and respiratory center result in respiratory compromise Cranial nerve involvement leads to paralysis of the pharynx and vocal cords, further posing difficulties in breathing Respiratory compromise leads to most deaths in the paralytic form.127 Typically, 50% of patients with any paralysis exhibit some degree of residual deficits, although most improve A 10% mortality is now reported in the patients with the paralytic form Before mechanical ventilation, 60% of the individuals died.127 Early in the course of pharyngeal infection, throat cultures may reveal poliovirus Later in the course, a stool culture becomes increasingly helpful Spinal fluid culture has lower sensitivity Usually, the results of routine laboratory tests are unremarkable CSF findings are characteristic of aseptic meningitis In the first few hours after the onset of symptoms, polymorphonuclear leukocytes may predominate However, within 12 hours, the predominance of lymphocytes is seen.127 Numerous other clinical manifestations may occur With myocarditis, the heart is extremely sensitive to development of arrhythmias Hypertension is well recognized and can be severe enough to cause encephalopathy Analgesics, including opiates, may be required for pain relief Hot packs have been noted to be effective when applied every to hours Constipation and bladder paralysis are major issues early in the course and should be monitored closely The risk of aspiration and airway compromise necessitates a high level of vigilance If the patient demonstrates respiratory compromise, a tracheostomy is indicated with accompanying mechanical ventilation.127 Use of antiviral agents is debated Additionally, some authors argue that corticosteroids are not indicated in enteroviral infections.127 Children with mild weakness generally have full recovery If paralysis is present, the recovery remains ongoing for years, with 80% realized by months.127 Adults may have new symptoms long after the infection resolves, including weakness and muscle atrophy that is related to continued normal attrition of anterior horn cells.128 Polio-Like Syndromes Polio-like syndromes have been reported, with West Nile virus and multiple subtypes of enterovirus (most notably D68 and A71) being prominent agents.129–131 These cases are often associated with a prior illness (either gastrointestinal or respiratory) 843 and may present with respiratory failure and an acute flaccid paralysis of one or more limbs consistent with anterior horn cell disease Interestingly, these clusters of cases with acute flaccid myelitis have predominantly occurred on alternate years Between 2014 and 2018, there were 480 cases reported in 40 states (https://www.cdc.gov/acute-flaccid-myelitis/hcp/clinicalmanagement.html) Consistent clinical characteristics include rapid progression from hours to days of flaccid weakness These findings are typically asymmetric, predominantly involving the upper extremities (C5, C6) and proximal greater than distal CSF pleocytosis as well as elevated protein is the rule Culture of the virus in the CSF is very rare and should not be expected Magnetic resonance imaging (MRI) of the brain and spine are very important Injury of the spinal motor neurons is best visualized on T2 and fluid attenuation inverse recovery, with multiple levels involved, at times involving the entire spine and later in the course involving nerve root enhancement Brainstem lesions may be seen as well Supratentorial lesions are observed in approximately 10% of MRI studies Cranial nerve abnormalities may accompany limb weakness and mostly involve CN VI, CN VII, CN IX, and CN X.130 There are variable reports of seizures, altered mental status, and bowel/ bladder dysfunction Sensation is classically spared, as in polio, but there are reports of some involvement Multiple treatment modalities have been tried, but there are no definitive treatments that have been shown to be effective The Centers for Disease Control and Prevention has provided the Summary of Interim Considerations, a consensus statement emphasizing the lack of current treatment efficacy (www.cdc.gov/acute-flaccid-myelitis/ hcp/clinical-management.html#summary-interim-considerations) New studies are on the horizon that will hopefully offer efficacious treatment options Organophosphate and Carbamate Poisoning The clinician must always maintain a high index of suspicion and consider poisoning in the differential diagnosis in patients with altered mental status, respiratory symptoms, or weakness (see also Chapters 125 and 126) Zwiener and Ginsburg132 reported in their study of 37 children with organophosphate or carbamate poisonings that 43% of these patients were evaluated by their primary care doctor, and pesticide toxicity was not suspected Patients commonly not provide a known history of exposure Exposure to these substances may occur as inhalation, ingestion, or dermal contact In one study of 37 infants and children with organophosphate and carbamate poisonings, 76% of these patients ingested these substances (which were improperly stored), 16% had transcutaneous exposure (through contact with treated carpets, linens, and lawns), and 8% were poisoned by an unknown etiology.132 Cholinesterase, which is present in the neuromuscular junction, is irreversibly inhibited by organophosphates and reversibly inhibited by carbamate compounds Therefore, a constellation of muscarinic, nicotinic, and central nervous system symptoms may occur Symptoms may originate from various systems Muscarinic symptoms include miosis, excessive salivation, sweating, lacrimation, diarrhea, urination, and bradycardia In severe poisonings, flaccid paralysis with areflexia is common In moderate poisonings, muscle fasciculations may be present CNS symptoms include coma and seizures; however, seizures are less common in carbamate toxicity.133 Pulmonary symptoms—including bronchoconstriction, increased pulmonary secretions, and wheezing—have been reported.134 In one study of 52 children 844 S E C T I O N V I Pediatric Critical Care: Neurologic with organophosphate or carbamate poisoning, 100% of these patients exhibited hypotonia, stupor, or coma.135 With further analysis of the 16 patients with organophosphate poisoning, the other common symptoms included miosis (56%), salivation (37%), pulmonary edema (37%), diarrhea (30%), and bradycardia (25%).135 Various cardiac rhythms may occur with pathologic signs of cardiotoxicity.136 Overall, carbamate poisonings are usually less severe and shorter in duration, although the symptoms are essentially the same as those found in organophosphate poisonings.137 If organophosphate and carbamate compounds are ingested, gastric lavage and activated charcoal should be initiated If contaminated, the patient’s skin and hair should be rinsed and cleansed thoroughly with soap, and clothes should be changed to reduce further exposure.133 In both forms of poisonings, atropine is used as an antidote for the muscarinic symptoms Treatment with atropine, however, does not reverse the nicotinic symptoms, which include muscle weakness and respiratory failure Atropine should be administered as quickly as possible and in adequate doses In children older than 12 years, the dosing is to mg IV every 10 to 30 minutes In children younger than 12 years, the initial dose is 0.05 mg/kg with maintenance doses of 0.02 to 0.05 mg/kg over 10 to 30 minutes.134 In organophosphate and carbamate poisonings, the atropine dose is to 10 times greater than conventional atropine dosing.134 Atropine should be continued until the muscarinic symptoms begin to abate The signs of atropinization include mydriasis, tachycardia, and xerostomia; they help provide parameters for adequate dosing.138 Atropine should be continued for at least 24 hours after severe exposures and then tapered if symptoms are improving.134 Pralidoxime chloride, the only cholinesterase reactivator in the United States, is an antidote for only the nicotinic symptoms of organophosphate poisonings Therefore, atropine must be used concomitantly Pralidoxime chloride does not help in carbamate exposures Various doses have been reported for pralidoxime in patients older than 12 years A conservative dose is 0.5 to 1.0 g IV over 15 to 30 minutes, repeated every 10 to 12 hours, beginning to hours after the initial dose More recently, another study suggests a 2-g loading dose with a continuous infusion of g/h for 48 hours These doses have not been directly compared to each other In patients younger than 12 years, the dose is 25 to 50 mg/kg IV over 15 to 30 minutes, repeated every 10 to 12 hours, beginning to hours after the initial dose (maximum, g/dose).134,139,140 After the antidotes are given, the mainstay of treatment is supportive If necessary, ventilation should be provided until the patient regains respiratory strength Suctioning of secretions in both the oropharynx and proximal conducting airway is essential Seizures should be treated with diazepam or lorazepam Cardiac monitoring should be implemented because complex ventricular arrhythmias may occur.136,141 Early feeding may prolong hospital stay.142 Death usually occurs as a result of respiratory arrest and pulmonary complications, including excessive secretions, edema, and bronchoconstriction.134 Diagnosis is based on clinical findings and response to antidote medications Serum and red blood cell cholinesterase levels should be obtained to assist in the diagnosis of organophosphate poisoning Treatment should be initiated immediately and not delayed while waiting for cholinesterase level results Cholinesterase levels not assist in the diagnosis of carbamate exposure because the reversal of the enzyme occurs too rapidly to be quantified Key References Chiang LM, Darras BT, Kang PB Juvenile myasthenia gravis Muscle Nerve 2009;39:423-431 Dimario Jr FJ, Edwards C Autonomic dysfunction in childhood Guillain-Barre syndrome J Child Neurol 2012;27:581-586 Finkel R, Mercuri E, Darras B, et al Nusinersin versus sham control in infantile-onset spinal muscular atrophy N Engl J Med 2017;337: 1723-1732 Greenstein P Tick paralysis Med Clin North Am 2002;86:441-446 Mendell J, Al-Zaidy S, Shell R, et al Single-dose gene-replacement therapy for spinal muscular atrophy N Engl J Med 2017;377: 1713-1722 Messacar K, Schreiner TL, Maloney JA, et al A cluster of acute flaccid paralysis and cranial nerve dysfunction temporarily associated with an outbreak of enterovirus D68 in children in Colorado, USA Lancet 2015;385:1662-1671 Patwa HS, Chaudhry V, Katzberg H, et al Evidence-based guideline: intravenous immunoglobulin in the treatment of neuromuscular disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2012;78:1009-1015 Spika J, Shaffer N, Hargrett-Bean N, et al Risk factors for infant botulism in the United States Am J Dis Child 1989;143:828-832 Underwood K, Rubin S, Deakers T, et al Infant botulism: a 30-year experience spanning the introduction of botulism immune globulin intravenous in the intensive care unit at Children’s Hospital Los Angeles Pediatrics 2007;120:e1380-e1385 Zinman L, Ng E, Bril V IV immunoglobulin in patients with myasthenia gravis: a randomized controlled trial Neurology 2007;68:837-841 The full reference list for this chapter is available at ExpertConsult.com e1 References Rantala H, Uhari M, Niemela M Occurrence, clinical manifestations, and prognosis of Guillain-Barre syndrome Arch Dis Child 1991;66:706-709 Hart D, Rojas L, Rosario J, et al Childhood Guillain-Barre syndrome in Paraguay, 1990 to 1991 Ann Neurol 1994;36:859-863 Ammache Z, Afifi A, Brown C, et al Childhood Guillain-Barre syndrome: clinical and electrophysiologic features predictive of outcome J Child Neurol 2001;6:477-483 Parra B, Lizarazo J, Jiménez-Arango JA, et al Guillain–Barré Syndrome associated with Zika Virus infection in Colombia N Engl J Med 2016;375:1513-1523 Chang AY, Lynch R, Martins K, et al Long-term clinical outcomes of Zika-associated Guillain-Barré syndrome Emerg Microbes Infect 2018;7:148 Bradshaw D, Jones H Guillain-Barre syndrome in children: clinical course, electrodiagnosis, and prognosis Muscle Nerve 1992;15: 500-506 Jones H Guillain-Barre syndrome: clinical presentation, diagnosis, and therapy J Child Neurol 1996;11:4-12 Rantala H, Uhari M, Cherry J, et al Risk factors of respiratory failure in children with Guillain-Barre syndrome Pediatr Neurol 1995;13:289-292 Dimario Jr FJ, Edwards C Autonomic dysfunction in childhood Guillain-Barre syndrome J Child Neurol 2012;27:581-586 10 Emmons P, Blume W, DuShane J Cardiac monitoring and demand pacemaker in Guillain-Barre syndrome Arch Neurol 1975;32:59-61 11 Rumalla K, Reddy AY, Letchuman V, Mittal MK Hyponatremia in Guillain-Barré Syndrome J Clin Neuromuscul Dis 2017;18:207-217 12 Asbury A, Cornblath D Assessment of current diagnostic criteria for Guillain-Barre syndrome Ann Neurol 1990;27(suppl):S21-S24 13 Agrawal S, Peake D, Whitehouse WP Management of children with Guillain-Barre syndrome Arch Dis Child Educ Pract Ed 2007;92: 161-168 14 Hughes RAC, Wijdicks EFM, Barohn R, et al Practice parameter: immunotherapy for Guillain-Barré syndrome: report of the Quality Standards Subcommittee of the American Academy of Neurology Neurology 2003;61:736-740 15 Patwa HS, Chaudhry V, Katzberg H, et al Evidence-based guideline: intravenous immunoglobulin in the treatment of neuromuscular disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2012;78:1009-1015 16 Hughes RA, van Doorn PA Corticosteroids for Guillain-Barre syndrome Cochrane Database Syst Rev 2012;15:8:CD001466 17 Hughes RA, Swan AV, van Doorn PA Intravenous immunoglobulin for Guillain-Barre syndrome Cochrane Database Syst Rev 2014; 9:CD002063 18 Vajsar J, Sloane A, Wood E, et al Plasmapheresis vs intravenous immunoglobulin in childhood Guillain-Barre syndrome Arch Pediatr Adolesc Med 1994;148:1210-1212 19 Korinthenberg R, Monting J Natural history and treatment effects in Guillain-Barre syndrome: a multicentre study Arch Dis Child 1996;74:281-287 20 Korinthenberg R, Schessl J, Kirschner J, et al Intravenously administered immunoglobulin in the treatment of childhood GuillainBarré Syndrome: a randomized trial Pediatrics 2005;116:8-14 21 Chiba A, Kusunoki S, Shimizu T, et al Serum IgG antibody to ganglioside GQ1b is a possible marker of Miller Fisher syndrome Ann Neurol 1992;31:677-679 22 Jacobs B, Endtz H, van der Meche F, et al Serum anti-GQ1b IgG antibodies recognize surface epitopes on Campylobacter jejuni from patients with Miller Fisher syndrome Ann Neurol 1995;37:260-264 23 Chiba A, Kusunoki S, Obata H, et al Serum anti-GQ1b IgG antibody is associated with ophthalmoplegia in Miller Fisher syndrome and Guillain-Barre syndrome: clinical and immunohistochemical studies Neurology 1993;43:1911-1917 24 Petzold A, Brettschneider J, Jin K, et al CSF protein biomarkers for proximal axonal damage improve prognostic accuracy in the acute phase of Guillain-Barré Syndrome Muscle Nerve 2009;40:42-49 25 Petzold A, Hinds N, Murray NMF, et al CSF neurofilament levels: a potential prognostic marker in Guillain-Barre syndrome Neurology 2006;67:1071-1073 26 Drachman D Myasthenia gravis N Engl J Med 1994;330: 1797-1810 27 Andrews P, Massey J, Howard J, et al Race, sex, and puberty influence onset, severity, and outcome in juvenile myasthenia gravis Neurology 1994;44:1208-1214 28 Bartoccioni E, Scuderi F, Minicuci GM, et al Anti-MuSK antibodies: correlation with myasthenia gravis severity Neurology 2006;67:504-507 29 Niks EH, Verrips A, Semmekrot BA, et al A transient neonatal myasthenic syndrome with anti-musk antibodies Neurology 2008;70:1215-1216 30 Leite MI, Jacob S, Viegas S, et al IgGI antibodies to acetylcholine receptors in ‘seronegative’ myasthenia gravis Brain 2008;131: 1940-1952 31 Deymeer F, Gungor-Tuncer O, Yilmaz V, et al Clinical comparison of anti-MuSK- vs anti-AChR-positive and seronegative myasthenia gravis Neurology 2007;68:609-611 32 Chiang LM, Darras BT, Kang PB Juvenile myasthenia gravis Muscle Nerve 2009;39:423-431 33 The Muscle Study Group A trial of mycophenolate mofetil with prednisone as initial immunotherapy in myasthenia gravis Neurology 2008;71:394-399 34 Hehir MK, Burns, TM, Alpers J, et al Mycophenolate mofetil in Ach-R-Antibody-Positive Myasthenia Gravis: outcomes in 102 patients Muscle Nerve 2010;41:593-598 35 Sanders DB, Hart IK, Mantegazza R, et al An international, phase III, randomized trial of mycophenolate mofetil in myasthenia gravis Neurology 2008;71:390-391 36 Youssef S Thymectomy for myasthenia gravis in children J Pediatr Surg 1983;18:537-541 37 Adams C, Theodorescu D, Murphy E, et al Thymectomy in juvenile myasthenia gravis J Child Neurol 1990;5:215-218 38 Rodriguez M, Gomez M, Howard F, et al Myasthenia gravis in children: long-term follow-up Ann Neurol 1983;13:504-510 39 Fink M Treatment of the critical ill patient with myasthenia gravis In: Ropper A, ed Neurological and Neurosurgical Intensive Care New York: Raven Press; 1993 40 Thomas C, Mayer S, Gungor Y, et al Myasthenic crisis: clinical features, mortality, complications, and risk factors for prolonged intubation Neurology 1997;48:1253-1260 41 Anlar B, Ozdirim E, Renda Y, et al Myasthenia gravis in childhood Acta Paediatr 1995;85:838-842 42 Qureshi A, Choudhry M, Akbar M, et al Plasma exchange versus intravenous immunoglobulin treatment in myasthenic crisis Neurology 1999;52:629-632 43 Zinman L, Ng E, Bril V IV immunoglobulin in patients with myasthenia gravis: a randomized controlled trial Neurology 2007;68:837-841 44 Mayer S Intensive care of the myasthenic patient Neurology 1997; 48(suppl 5):S70-S75 45 Adams S, Mathews J, Grammer L Drugs that may exacerbate myasthenia gravis Ann Emerg Med 1984;13:532-538 46 Kimura K, Nezu A, Kimura S, et al A case of myasthenia gravis in childhood associated with chronic inflammatory demyelinating polyradiculoneuropathy Neuropediatrics 1998;29:108-112 47 Gotkine M, Fellig, Abramsky O Occurrence of CNS demyelinating disease in patients with myasthenia gravis Neurology 2006;67:881-883 48 Namba T, Brown S, Grob D Neonatal myasthenia gravis: report of two cases and review of the literature Pediatrics 1970;45:488-504 49 Ohta M, Matsubara F, Hayashi K, et al Acetylcholine receptor antibodies in infants of mothers with myasthenia gravis Neurology 1981;31:1019-1022 e2 50 Lefvert A, Osterman P Newborn infants to myasthenic mothers: a clinical study and an investigation of acetylcholine receptor antibodies in 17 children Neurology 1983;33:133-138 51 Engel A, Ohno K, Milone M Congenital myasthenic syndromes caused by mutations in acetylcholine receptor genes Neurology 1997;48(suppl 5):S28-S35 52 Dworkin M, Shoemaker P, Anderson D Tick paralysis: 33 human cases in Washington State, 1946-1996 Clin Infect Dis 1999;29: 1435-1439 53 Greenstein P Tick paralysis Med Clin North Am 2002;86:441-446 54 Gorman R, Snead O: Tick paralysis in three children Clin Pediatr 17:249-251, 1978 55 Needham G Evaluation of five popular methods for tick removal Pediatrics 1985;75:997-1002 56 Grattan-Smith P, Morris J, Johnston H, et al Clinical and neurophysiological features of tick paralysis Brain 1997;120:1975-1987 57 Donaldson MR, Yoon G, Fu YH, Ptacek LJ Andersen-Tawil syndrome: a model of clinical variability, pleiotropy, and genetic heterogeneity Ann Med 2004;36(suppl 1):92-97 58 Tawil R, Ptacek LJ, Pavlakis SG, et al Andersen’s syndrome: potassium sensitive periodic paralysis, ventricular ectopy and dysmorphic features Ann Neurol 1994;35:326-330 59 Miller TM, Dias da Silva MR, Miller HA, et al Correlating phenotype and genotype in the periodic paralyses Neurology 2004;63: 1647-1655 60 Ptacek L, Tawil R, Griggs R, et al Dihydropyridine receptor mutations cause hypokalemic periodic paralysis Cell 1994;77:863-868 61 Sugiura Y, Makita N, Li L, et al Cold induces shifts of voltage dependence in mutant SCN4A, causing hypokalemic periodic paralysis Neurology 2003;61:914-918 62 Matthews E, Labrum R, Sweeney MG, et al Voltage sensor charge loss accounts for most cases of hypokalemic periodic paralysis Neurology 72:1544-1547, 2009 63 Links T, Smit A, Molenaar W, et al Familial hypokalemic periodic paralysis clinical, diagnostic and therapeutic aspects J Neurol Sci 1994;122:33-43 64 Schiller T, Auerbach P Hypokalemic periodic paralysis: two case reports Pediatr Emerg Care 1988;4:183-186 65 Smith W Periodic paralysis: report of two fatal cases J Nerv Men Dis 1937;90:210-215 66 Talbott J Periodic paralysis: a clinical syndrome Medicine 1941;20:85-143 67 Pudenz R, McIntosh J, McEachern D Role of potassium in familial periodic paralysis JAMA 1938;111:2253-2258 68 Resnick J, Engel W Myotonic lid lag in hypokalaemic periodic paralysis J Neurol Neurosurg Psychiatry 1967;30:47-51 69 Zierler K, Andres R Movement of potassium into skeletal muscle during spontaneous attack in family periodic paralysis J Clin Invest 1957;36:730-737 70 Charness M Clinical conferences at The Johns Hopkins Hospital Hypokalemic periodic paralysis Johns Hopkins Med J 1978;143: 148-153 71 Griggs R, Resnick J, Engel W Intravenous treatment of hypokalemic periodic paralysis Arch Neurol 1983;40:539-540 72 Kunin A, Surawicz B, Sims E Decrease in serum potassium concentrations and appearance of cardiac arrhythmias during infusion of potassium with glucose in potassium-depleted patients N Engl J Med 1962;266:228-233 73 Griggs R, Engel W, Resnick J Acetazolamide treatment of hypokalemic periodic paralysis: prevention of attacks and improvement of persistent weakness Ann Intern Med 1970;73:39-48 74 Torres C, Griggs R, Moxley R, et al Hypokalemic periodic paralysis exacerbated by acetazolamide Neurology 1981;31:1423-1428 75 Miller J, Quillian W, Cleveland W Nonfamilial hypokalemic periodic paralysis and thyrotoxicosis in a 16-year-old male Pediatrics 1997;100:412-414 76 Gamstorp I Adynamia episodica hereditaria Acta Paediatr 1956;45(suppl 108):1-126 77 George Jr AL, Ledbetter DH, Kallen RG, et al Assignment of a human skeletal muscle sodium channel alpha-subunit gene (SCN4A) to 17q23.1-25.3 Genomics 1991;9:555-556 78 Fontaine B, Khurana T, Hoffman E, et al Hyperkalemic periodic paralysis and the adult muscle sodium channel alpha-subunit gene Science 1990;250:1000-1002 79 Dyken M, Timmons G Hyperkalemic periodic paralysis with hypocalcemic episode Arch Neurol 1963;9:508-517 80 Herman RH, McDowell MK Hyperkalemic paralysis (adynamia episodica hereditaria) Report of four cases and clinical studies Am J Med 1963;35:749-767 81 Lisak R, Lebeau J, Tucker S, et al Hyperkalemic periodic paralysis and cardiac arrhythmia Neurology 1972;22:810-815 82 McArdle B Adynamia episodica hereditaria and its treatment Brain 1962;85:121-148 83 Layzer R, Lovelace R, Rowland L Hyperkalemic periodic paralysis Arch Neurol 1967;16:455-472 84 Long S Infant botulism Pediatr Infect Dis J 2001;20:707-709 85 Midura T, Arnon S Infant botulism: identification of Clostridium botulinum and its toxins in feces Lancet 1976;2:934-935 86 Shapiro R, Hatheway C, Swerdlow D Botulism in the United States: a clinical and epidemiologic review Ann Intern Med 1998; 129:221-228 87 Chia J, Clark J, Ryan C, et al Botulism in an adult associated with food-borne intestinal infection with Clostridium botulinum N Engl J Med 1986;315:239-241 88 Griffin P, Hatheway C, Rosenbaum R, et al Endogenous antibody production to botulinum toxin in an adult with intestinal colonization botulism and underlying Crohn’s disease J Infect Dis 1997; 175:633-637 89 McCroskey L, Hatheway C Laboratory findings in four cases of adult botulism suggest colonization of the intestinal tract J Clin Microbiol 1988;26:1052-1054 90 Long S, Gajewski J, Brown L, et al Clinical, laboratory, and environmental features of infant botulism in Southeastern Pennsylvania Pediatrics 1985;75:935-941 91 Long S Epidemiologic study of infant botulism in Pennsylvania: Report of the Infant Botulism Study group Pediatrics 1985;75: 928-934 92 Spika J, Shaffer N, Hargrett-Bean N, et al Risk factors for infant botulism in the United States Am J Dis Child 1989;143: 828-832 93 Arnon S, Damus K, Thompson B, et al Protective role of human milk against sudden death from infant botulism J Pediatr 1982; 100:568-573 94 Schreiner M, Field E, Ruddy R Infant botulism: a review of 12 years’ experience at the Children’s Hospital of Philadelphia Pediatrics 1991;87:159-165 95 L’Hommedieu C, Polin R Progression of clinical signs in severe infant botulism Therapeutic implications Clin Pediatr (Phila) 1981;20:90-95 96 Thompson J, Glasgow L, Warpinski J, et al Infant botulism: clinical spectrum and epidemiology Pediatrics 1980;66:936-942 97 L’Hommedieu C, Stough R, Brown L, et al Potentiation of neuromuscular weakness in infant botulism by aminoglycosides J Pediatr 1979;95:1065-1070 98 Cornblath D, Sladky J, Sumner A Clinical electrophysiology of infantile botulism Muscle Nerve 1983;6:448-452 99 Wilson R, Morris J, Snyder J, et al Clinical characteristics of infant botulism in the United States: a study of the non-California cases Pediatr Infect Dis 1982;1:148-150 100 Arnon SS, Schechter R, Maslanka SE, et al Human botulism immune globulin for the treatment of infant botulism NEJM 2006;354:462-471 101 Underwood K, Rubin S, Deakers T, et al Infant botulism: a 30year experience spanning the introduction of botulism immune globulin intravenous in the intensive care unit at Children’s Hospital Los Angeles Pediatrics 2007;120:e1380-e1385 ... and raises the trunk from supine, the head falls backward in a limp fashion It is thought that this is not due to paralysis of the neck muscles because it can occur in the nonparalytic form The... involvement leads to paralysis of the pharynx and vocal cords, further posing difficulties in breathing Respiratory compromise leads to most deaths in the paralytic form.127 Typically, 50% of patients... few hours after the onset of symptoms, polymorphonuclear leukocytes may predominate However, within 12 hours, the predominance of lymphocytes is seen.127 Numerous other clinical manifestations