Neurologic Emergencies

Authors

Judith Toski Welsh, MD, Emergency Services Institute, Cleveland Clinic, Cleveland, OH

Purva Grover, MD, FACEP, Emergency Services Institute, Cleveland Clinic, Cleveland, OH

Neurologic emergencies in children generally manifest as problems with movement, vision, sensation, alertness, or cognition. Seizures, particularly febrile seizures, are a common ED presentation. Complaints of headache are also fairly common among children and adolescents. Other disease processes reviewed are less common, but may affect diagnostic evaluation, management and disposition.

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Seizures

Pediatric seizures account for about 1% of community emergency department (ED) visits, and about 2% of visits to children’s hospital EDs.¹ Infants and children younger than 5 years of age are more likely to be transported to an ED for evaluation of a seizure.² Febrile seizures are the most common cause of seizures in children with recurrence rates variable, between 14% and 65%, with the overwhelming majority occurring within 2 years of the initial episode.³

Most neurologists use the International Classification of Epileptic Seizures to classify seizures based upon clinical features and findings on electroencephalography (EEG): generalized, focal, and unknown (spasms).

Type of Seizure	Motor/Sensory/Cognitive Manifestations	Age Considerations
Generalized	Impaired level of consciousness (LOC) Bilateral motor movements Convulsive (tonic, clonic) or nonconvulsive (absence)	Tonic clonic and absence seizures rare in children younger than 2 years of age and never occur in newborn
Focal (partial)	Originate within one hemisphere May or may not have change in LOC May have sensory, motor, behavioral, autonomic symptoms	Accounts for > 50% of new-onset epilepsy in children4 Incidence highest in first of life, declines with age
Epileptic Spasms	May be focal, generalized, or both Controversial — insufficient knowledge to classify	Includes infantile spasms

Many conditions in children can be confused with seizures, including syncope, breath-holding spells, rigors or chills, dystonia, or tics. Syncope should be considered in children who do not have a postictal period, or if the child complains of palpitations. Breath-holding spells occur most commonly in infants between 6 and 18 months of age, and often occur while the child is upset and crying. The child may become limp and appear ashen, and loss of consciousness can occur with or without clonus. These episodes are brief, usually lasting < 1 minute.

A comprehensive history and physical exam should be performed on all patients with suspected seizure activity. A report of the event from an eyewitness is one of the most helpful pieces of information. A verbal child can also provide helpful data.

• What was happening before the event occurred? Did the child feel ill that day? Has the child suffered any recent head injuries, headaches, or other neurologic symptoms?
• What was seen during the event? Was there unilateral or bilateral shaking? Were there eye movements that appeared unusual? Was there loss of consciousness or frothing at the mouth? Was there incontinence?
• After the event: Was there lethargy or confusion present? What did the patient remember about the event?
• Precipitating factors: Has the child had any recent illnesses? Is there concern for exposure to toxic substances? Is the child taking any medications? Are there any concerns that someone may be maltreating the child?

A full physical exam should start with a careful evaluation of vital signs, including blood pressure. Physicians should look for signs of injury, especially evidence of head trauma. Although children with mild head injury are no more at risk of seizure than the general population, altered state of consciousness (77%) and seizures (43-50%) are common in children with abusive head injury.⁵ A bulging fontanel in an infant suggests increased intracranial pressure. A full neurological exam should be performed, including an assessment of gait if developmentally appropriate. A careful skin exam may reveal signs of a neurocutaneous disorder. Neck stiffness or other meningeal signs may be signs of meningitis and should signal the need for a lumbar puncture. Symptoms of a specific toxidrome, including sympathiometic intoxication, anticholinergic intoxication, organophosphate intoxication, and benzodiazepine withdrawal should be identified.

Laboratory evaluation in a child who is neurologically normal and recovers uneventfully from a brief first seizure should be tailored based on the child’s clinical presentation. Laboratory tests should be ordered based on individual clinical circumstances that include suggestive historic or clinical findings such as vomiting, diarrhea, dehydration, or failure to return to baseline alertness. An extensive lab workup, including lumbar puncture, is not always necessary. A blood glucose level should be obtained in all children.

Children with the highest pretest probability of abnormal lab values are those who present to the ED with status epilepticus, hypothermia (< 36.5° C), or age younger than 1 month.⁶ Laboratory analysis of electrolytes and magnesium levels should be considered in children younger than 6 months of age with a first seizure, since they are at increased risk of an undiagnosed metabolic abnormality. Excessive dilution of formula can cause hyponatremia, and the effect of excess free water is more severe in smaller infants. Conversely, underdilution of formula can cause severe hypernatremia.

In addition, laboratory workup is indicated in children who present with a prolonged first seizure, a history of a metabolic disorder, dehydration or suspected excessive free water ingestion, or depressed level of consciousness. Lumbar puncture should be performed in children with a lengthy postictal period or any symptoms suggestive of meningitis or encephalitis.

Neuroimaging in Children with First Seizure

Parents frequently inquire about whether their child with a first seizure should have CT imaging. A developmentally normal child with a nonfocal neurologic exam who has returned to his/her normal baseline after a brief postictal period does not need an emergent CT scan of the brain, as there is a very low incidence of abnormal findings necessitating emergent management. Brain CT can be helpful in patients who are at high risk for abnormal imaging results. These include patients with:

• Focal seizure
• Focal deficits
• Ventriculoperitoneal shunt
• Persistent seizure activity
• Immunocompromise or coagulopathy
• Head trauma
• Altered mental status
• Signs of increased intracranial pressure (pupillary changes or vomiting)
• Evidence of neurocutaneous disorder
• Recent visit to a physician or health care worker⁷

Non-emergent neuroimaging with magnetic resonance imaging (MRI) is recommended for any child who has significant cognitive or motor impairment of unknown etiology, unexplained abnormalities on neurologic examination, seizure of partial onset with or without secondary generalization, EEG that does not represent benign partial epilepsy of childhood or primary generalized epilepsy, and for children younger than 1 year.

NATIONAL GUIDELINE/ACADEMIC RESOURCE

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Febrile seizure

A febrile seizure is a generalized seizure accompanied by fever (temperature ≥ 100.4° F or 38.2° C by any method), without a central nervous system infection, that usually occurs in infants and children between 6 to 60 months of age. Febrile seizures occur in 2-5% of all children and constitute the most common convulsive event in children younger than 60 months. Simple febrile seizures are defined as primary generalized seizures lasting < 15 minutes that do not recur within 24 hours. Complex febrile seizures are defined as focal, prolonged (≥15 minutes), and/or recurrent seizures within 24 hours.

The American Academy of Pediatrics does not recommend any laboratory testing or neuroimaging routinely in a well-appearing child with a simple febrile seizure. A lumbar puncture should be performed in any child with clinical suspicion of meningitis. Lumbar puncture should also be considered in children who have been pretreated with antibiotics (i.e. suspicion for partially treated bacterial meningitis), infants who have not be appropriately immunized against Haemophilus influenza type b (Hib) or Streptococcus pneumonia, or when immunization status cannot be determined.

NATIONAL GUIDELINE/ACADEMIC RESOURCE

Febrile Seizures: Guideline for the Neurodiagnostic Evaluation of the Child With a Simple Febrile Seizure

http://pediatrics.aappublications.org/content/127/2/389.long

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Status Epilepticus

Status epilepticus is defined as 5 minutes or more of 1) continuous clinical and/or electrographic seizure activity or 2) recurrent seizure activity without recovery (return to baseline) between seizures.

Table: Differential Diagnosis

Acute Etiologies

Metabolic disturbances: electrolyte abnormalities, hypoglycemia, renal failure Sepsis Central nervous system infection: meningitis, encephalitis, abscess Stroke: ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, cerebral sinus thrombosis Head trauma with or without epidural or subdural hematoma Drug issues/drug toxicity: Withdrawal from opioid, benzodiazepine, barbiturate, or alcohol Non-compliance with AEDs Hypoxia, cardiac arrest Hypertensive encephalopathy, posterior reversible encephalopathy syndrome Autoimmune encephalitis (i.e., anti-NMDA receptor antibodies, anti-VGKC complex antibodies), paraneoplastic syndromes

Chronic Etiologies

Preexisting epilepsy: breakthrough seizures or discontinuation of AEDs CNS tumors Remote CNS pathology (e.g., stroke, abscess, TBI, cortical dysplasia)

Special Considerations in Children

Acute symptomatic SE is more frequent in younger children with SE Prolonged febrile seizures are the most frequent cause of SE in children CNS infections, especially bacterial meningitis, inborn errors of metabolism, and ingestion are frequent causes of SE

Diagnostic Evaluation

All patients should receive a blood glucose level, monitoring of vital signs, a head CT scan, and laboratory testing — complete blood count, basic metabolic panel, calcium (total and ionized), magnesium, and anti-epileptic drug levels as appropriate. Continuous EEG monitoring may be considered based on clinical presentation. Brain imaging (MRI) and lumbar puncture are based on clinical presentation. Comprehensive toxicology panel should be considered and should include toxins that frequently cause seizures (i.e., isoniazid, tricyclic antidepressants, theophylline, cocaine, sympathomimetics, alcohol, organophosphates, and cyclosporine). Other laboratory tests that may be considered include liver function tests, coagulation studies, arterial blood gas, anti-epileptic drug levels, toxicology screen (urine and blood), ammonia levels, and inborn errors of metabolism.

Treatment

Table: Critical Care Treatment Outline for Convulsive and Non-convulsive Status Epilepticus

Critical Care Treatment	Timing (minutes post-seizure onset)	Goals
Non-invasive airway protection and gas exchange with head positioning	Immediate (0-2 minutes)	Maintain airway patency, avoid snoring, administer O2
Intubation (if airway/gas exchange compromised or elevated ICP suspected	Immediate (0-2 minutes)	Establish secure oxygenation and ventilation
Vital signs: O2, saturation, BP, HR	Immediate (0-2 minutes)	Establish and support baseline vital signs
Vasopressor support of BP if SBP < 90 mmHg or MAP < 70	Immediate (5-15 minutes)	Support CPP
Finger stick blood glucose	Immediate (0-2 minutes)	Diagnose hypoglycemia
Peripheral IV access Emergent initial AED therapy Nutrient resuscitation (thiamine given before dextrose; dextrose)		Stop seizure Reverse thiamine deficiency, treat hypoglycemia
Urgent SE control therapy with AED	Immediate after initial AED given (5-10 minutes)	Stop seizure
Triage lab test panel	Immediate (5 minutes)	Diagnose life-threatening metabolic condition
Refractory SE treatment	Urgent (0-60 minutes)	Stop seizures; treatment strategies based on individual patient response and AED concentrations (if applicable)
Urinary catheter	Urgent (0-60 minutes)	Evaluate systemic circulation
Continuous EEG	Urgent (15-60 minutes)	Evaluate for NCSE if not waking up after clinically obvious seizures cease
Intracranial pressure monitoring (depending on clinical presentation)	Urgent (0-60 minutes of imaging diagnosis)	Measure and control ICP
AED – antiepileptic drug; BP – blood pressure; CPP – cerebral perfusion pressure; CT – computed tomography; EEG – electroencephalogram; HR – heart rate; ICP – intracranial pressure; LP – lumbar puncture; MAP – mean arterial pressure; MRI – magnetic resonance imaging; SBP – systolic blood pressure Adapted from: Brophy GM, Bell R, Claassen J, et al. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 2012;17:3-23.

As with any critically ill patient, the initial goals of management are securing an airway, providing supplemental oxygen, and rapid placement of IV access. Stabilization of the cervical spine is appropriate if trauma cannot be ruled out. Termination of the seizure is also a high priority. Assessment of blood glucose and treatment of symptomatic hypoglycemia should be undertaken as quickly as possible. D10 solution should be used in newborns (dose 5-10 mL/kg) and D25 should be given to children older than 2 months of age (dose 2-4 mg/kg). Ketogenic diets are often used in children with intractable epilepsy. It is unclear how the diets work to control seizures, but studies have demonstrated efficacy. Empiric treatment with glucose is not recommended in children on a ketogenic diet.⁸

In a child without hypoglycemia, the initial drug class of choice is a benzodiazepine. Lorazepam, diazepam, and midazolam are frequently used. Midazolam can be administered intranasally and many EMS protocols include this drug and route of administration, which can be considered as an alternative in patients with difficult-to-obtain IV access. Fosphenytoin should be used if benzodiazepines do not terminate the seizure. Fosphenytoin is preferred over phenytoin since it can be given more quickly and thus reaches therapeutic concentrations faster.⁹ If the seizure continues, a third-line agent must be chosen. Traditionally, phenobarbital is used (loading dose 20 mg/kg at a rate of 2 mg/minute). Phenobarbital causes significant respiratory depression, especially with benzodiazepines present. Alternatives that may not put the child at as high a risk of airway loss include levetiracetam and valproic acid. If seizures persist after the third-line medication is administered, another third-line medication should be used or pharmacologic coma induced. Propofol or midazolam can be loaded then continuously infused.¹⁰

Children may also present to the ED with acute exacerbations of their chronic seizure disorder. Many different factors influence the onset of breakthrough seizures. Medication nonadherence is a significant cause for breakthrough seizures, especially in patients younger than 30 years of age.¹¹ In a recent study, children who were perfectly adherent to their antiepileptic drug (AED) regimen starting from the time of diagnosis of epilepsy were more likely to be seizure-free 4 years later.¹² Other precipitating factors include:

• Sleep deprivation
• Flashing lights or playing video games
• Infection or intercurrent illness
• Emotional stress
• Medication issues other than nonadherence: change in formulation or drug-drug interactions

Commonly Used Medications to Control Chronic Seizures¹³

Medication	Maintenance Dose(mg/kg/day)	Side Effects
Carbemazepine	10-30	Double vision, ataxia, rash
Clobazam	< 2 years age: 0.5-1 >2 years age: 5-40	Rash, fatigue, ataxia
Lacosamide	200-400	Fainting, dizziness
Levatiracetam	20-60	Fatigue, irritability, headache
Oxcarbazepine	15-45	Fatigue, dizziness, rash, ataxia, vomiting, diarrhea
Phenobarbital	2-6	Dizziness, drowsiness, constipation, drug interactions
Phenytoin	4-8	Ataxia, rash, gingival hyperplasia, fatigue, hirsuitism
Topiramate	5-25	Sleepiness, confusion, diarrhea
Valproic acid	20-60	Weight gain, liver toxicity, tremor, thrombocytopenia
Vigabatrin	40-100	Loss of vision, sleepiness, tremor
Zonisamide	4-10	Kidney stones, rash, irritability

NATIONAL GUIDELINE/ADACEMIC RESOURCE

Guidelines for the Evaluation and Management of Status Epilepticus

https://www.neurocriticalcare.org/sites/default/files/pdfs/SE%20Guidelines%20NCS%200412.pdf

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Encephalopathy

Encephalopathy is a disruption of consciousness related to brain disease, injury, or dysfunction. Symptoms can range from mild memory loss and personality changes to delirium or coma. Subtle symptoms in infants and young children may be challenging to recognize. The underlying cause of the encephalopathy results from disruption of neurotransmission or cytotoxic injury and subsequent interference with the function of the reticular activating system and/or cerebral cortex.

Differential Diagnosis of Encephalopathy in Children

Structural	Toxic/Metabolic
Vascular: stroke, hemorrhage, vasculitis	Poisons: carbon monoxide, drugs of abuse, alcohol, overdoses of antidepressants or sedatives Heavy metal poisoning (lead, mercury)
Infection: meningitis, abscess, encephalitis	Electrolyte and Metabolic issues: Diabetic ketoacidosis, hypoglycemia, hyperammonemia, uremia
Tumor: mass effect, hydrocephalus	Hypoxia: Birth injury, multisystem organ failure, shock, strangulation
Injury: subdural, epidural, subarachnoid hemorrhage, Diffuse axonal injury/concussion, Shaken baby syndrome	Genetic causes: MELAS syndrome – mitochondrial encephalopathy, lactic acidosis and stroke-like episodes due to DNA mutation in mitochondria

Evaluation of encephalopathy begins with management of the ABCs – airway, breathing, and circulation – and a thorough history and physical examination. Important historical features include:

• Timing of onset
• Possible exposures or ingestion of medications or substances
• Medical history including: diagnosis of diabetes mellitus, inborn errors of metabolism, genetic disease, epilepsy, heart arrhythmias, hypertension, pregnancy, liver or kidney disease
• Presence of recent illness or fever
• History of trauma

Head-to-toe assessment should focus on looking for signs of head trauma, infection, or pupillary abnormalities suggestive of toxidrome or increased intracranial pressure. Seizure activity may be observed.

Lab Evaluation:

• Complete blood count: leukocytosis may suggest an infectious cause of altered mental status and need for specific studies.
• Electrolytes, including magnesium and serum osmolality.
  • Hyponatremia – often the result of gastrointestinal losses from diarrhea or vomiting and water intoxication. In young infants, water intoxication commonly occurs if formula is overdiluted or the infant is fed water. Osmotic water entry into brain cells causes cerebral edema. Symptoms include lethargy, agitation, nausea, and muscle cramps.¹⁴
  • Hypernatremia – water depletion caused by diarrhea most commonly; unsuccessful breastfeeding causing dehydration¹⁵; diabetes insipidus. Causes water loss from brain cells and shrinkage that predisposes to infarction, clotting, or abnormal bleeding.¹⁶ Correction should be gradual; rapid rehydration with free water can lead to central pontine myelinolysis and death or permanent neurological damage.
  • Hypoglycemia – severe, reversible cause of altered mental status in children. Idiopathic ketotic hypoglycemia is the most common reason for hypoglycemia in children 1-5 years of age and responds well to intravenous glucose.¹⁷ Inborn errors of metabolism, such as glycogen storage disorders, excessive insulin administration, and alcohol ingestion, can also lead to hypoglycemia.

Diabetic ketoacidosis and derangements of calcium and magnesium can also lead to altered mental status. Abnormally high or low calcium levels can also precipitate seizures.

• Blood and urine toxicology – alcohol, sedatives, and salicylate overdose can cause altered mental status
• Blood gas
• Renal function testing (blood urea nitrogen and creatinine)
• Hepatic function testing
• Ammonia
• Lactic acid, particularly if sepsis or metabolic derangement is suspected or confirmed
• Blood cultures
• Lumbar puncture and cerebrospinal fluid studies, to rule out infection or autoimmune disease

Imaging

CT without contrast is an appropriate first-line imaging study to evaluate for evidence of trauma, mass effect, or hypoxic injury. MRI is more difficult to obtain in an ED setting, but can be helpful to determine extent of brain injury or detecting infratentorial brain lesions or smaller areas of hypoxic injury.

Treatment

Supportive care is the cornerstone of management of the acutely encephalopathic patient. Definitive treatment depends on the underlying cause of the mental status change. The best ED management strategy is to treat all suspected causes at the beginning of the clinical course.¹⁸ In children with increased intracranial pressure, keeping the head elevated and maintaining normal serum CO₂ levels is appropriate. ED providers should consult with neurosurgery and critical care specialists to determine the need for surgical intervention, or medical intervention with intravenous mannitol, decadron, or hypertonic saline. Electrolyte disturbances should be corrected. Metabolic disease with increased ammonia levels may require hemodialysis. Oral feeding should be discontinued in any child with concern of metabolic disease, and IV dextrose should be started. Administration of empiric IV antibiotics and/or antiviral agents should be undertaken in any child with suspected sepsis, meningitis, or other acute infection.¹⁹

NATIONAL GUIDELINE/ACADEMIC RESOURCE

The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America

http://cid.oxfordjournals.org/content/47/3/303.full

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Migraines

Migraine headache is second only to viral illness as a cause of headaches in children presenting for emergency care. Migraines are characterized by intermittent, throbbing headache pain associated with photophobia, nausea, vomiting, abdominal pain, and relief with sleep. Migraine headaches can occur even in the youngest children, although the symptoms and signs may be vague and nonspecific. The diagnosis is difficult and should not be considered until other etiologies have been excluded. In toddlers, parents will relate a history of decreased activity, pale skin, and vomiting. In contrast to adolescents and adults, migraine pain in younger children is frequently bilateral.²⁰ Occipital headache is rare in children and its presence suggests a significant underlying disease.

The American Academy of Neurology guidelines state that strong evidence supports the use of ibuprofen and intranasal sumatriptan for migraine treatment in children and adolescents. Acetaminophen is a good treatment alternative. Little evidence supports the use of oral or subcutaneous triptans in pediatric patients.²¹ Dopamine antagonists, prochlorperazine and metoclopramide, are commonly used in ED treatment of pediatric patients, despite the lack of literature to support their use in this environment. A recent retrospective database review of ED migraine treatment in pediatric patients suggests that prochlorperazine is superior to metoclopramide in preventing a return to the ED within 72 hours, and that use of diphenhydramine is associated with an increased risk of revisit. Although the use of triptans is supported by research, they are very infrequently used in the ED.²² Administering intravenous fluids alone does not improve pain at 30 minutes into the course of ED treatment.²³

Table: Dosing of Medications for Acute Migraine and Estimation of Efficacy

Medication	Typical Dose and Route	Estimation of Efficacy
Dopamine Receptor Antagonist
Chlorpromazine Prochlorperazine	0.1 mg/kg to 25 mg IV or IM 10 mg IV or IM; 25 mg PR	83% effective in 1 hour IV/IM route effective in 67-88% at 30-60 minutes PR route had a positive outcome in all patients at 2 hours
			Promethazine	25 mg IM (caution with IV administration)	NA
Metoclopramide	10 mg IV	Effective in 34-46% at 30-60 minutes
Serotonin (5-HT1B/1D) Receptor Agonists: Triptans
Sumatriptan	6 mg SC 10 or 20 mg intranasal	Effective in 75% at discharge Mean pain score of the study group decreased significantly at 60 minutes
Ergot Derivatives
Dihydroergotamine	0.5 to 1 mg IM or IV	60% reduction in mean pain rating at 1 hour
NSAIDs
Ketorolac	30 mg IM or IV	Approximately 80% decrease in mean pain rating at 2 hours using 60 mg ketorolac IM Significant decrease in median pain score (approximately 57%) at 1 hour using 30 mg IV ketorolac
Diclofenac	75 mg IM	80% effective at 2 hours
Antiepileptics
Sodium valproate	300-1200 mg IV	Effective in 75% at 50 minutes
Abbreviations: IM – intramuscular; IV – intravenous; NSAIDs – nonsteroidal anti-inflammatory drugs; PR – per rectum
Adapted from: Gelfand AA, Goadsby PJ. A neurologist’s guide to acute migraine therapy in the emergency room. Neurohospitalist 2012;2:51-59.

A recent association between childhood migraine and a history of infantile colic has been established. A case-control study of 208 children showed that children who were colicky as infants were significantly more likely to have migraines between 6 and 12 years of age. Tension headaches were not associated with colic symptoms in infancy.²⁴ More research is necessary to further define this association. School-related stress and anxiety is a common trigger for headaches in pediatric patients.

NATIONAL GUIDELINE/ACADEMIC RESOURCE

A Neurologist’s Guide to Acute Migraine Therapy in the Emergency Room

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3737484/

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Idiopathic Intracraial Hypertension (Pseudotumor Cerebri)

Idiopathic intracranial hypertension (pseudotumor cerebri) (IIH) frequently presents with headache and about 70% of patients also have transient visual changes; visual loss or double vision. The classic patient is a young, overweight female with papilledema.

Most Common Symptoms in Idiopathic Intracranial Hypertension25

Headache Transient visual changes Pulsatile tinnitus Pain behind the eyes Double vision Sustained visual loss Perceived visual flashes of light (photopsia)

The most common physical exam finding in IIH is papilledema. Papilledema in IIH is typically bilateral. Sixth nerve (abducens) palsy and visual field deficits can also be present. Visual loss, which is usually reversible if treated early, is the major complication of this disease process.

Patients typically require CT and MR imaging of the brain to exclude mass, hemorrhage, or other etiology of increased intracranial pressure. Neuroimaging in patients with idiopathic intracranial hypertension typically shows normal brain parenchyma and ventricles. Lumbar puncture should be performed to measure intracranial pressure (ICP) and exclude cerebrospinal fluid (CSF) infection following normal brain imaging. Lumbar puncture shows increased opening pressure (> 25-30 cm H₂O). Draining CSF until the intracranial pressure normalizes usually significantly improves symptoms.²⁶

Modified Dandy criteria for the diagnosis of idiopathic intracranial hypertension

Signs and symptoms of increased intracranial pressure (headaches, nausea, vomiting, transient visual obscurations, papilledema). No localizing focal neurological signs except unilateral or bilateral sixth nerve paresis. CSF opening pressure ≥ 25 cm of water* but without cytological or chemical abnormalities. Normal neuroimaging adequate to exclude cerebral venous thrombosis—that is, MRI of the brain, often with additional sequences (CT or MR venography).

*The number of 25 cm of water is not an absolute cut-off, especially in children in whom CSF opening pressures as high as 28 cm of water have been documented to be normal

Treatment

The major goals of treatment in IIH are to alleviate symptoms of increased ICP, particularly headaches, and to preserve vision. In general, evaluation and treatment of potential contributing factors, including obesity, medication use, anemia, and medical headache management are the focus.

The treatment begins with the diagnostic lumbar puncture, which is often effective in transiently improving symptoms. Patients require a neurology consult.

NATIONAL GUIDELINE/ACADEMIC RESOURCES

Revised diagnostic criteria for the pseudotumor cerebri syndrome in adults and children

http://www.neurology.org/content/83/2/198.2.full

Update on the pathophysiology and management of idiopathic intracranial hypertension

http://jnnp.bmj.com/content/83/5/488.long

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Stroke

Stroke is an uncommon diagnosis in children. However, children with sickle cell disease, congenital heart lesions, hypercoagulable states, vascular dissection, or uncontrolled hypertension are at increased risk.

Table: Miscellaneous and Genetic Risk Factors for Stroke

Hereditary dyslipoproteinemia Familial hypoalphalipoproteinemia Familial hypercholesterolemia

Heritable disorders of connective tissue Ehlers-Danlos syndrome (type IV) Marfan syndrome Pseudoxanthoma elasticum Homocystinuria (cystathionine b-synthase deficiency, or 5, 20-MTHFR)

Organic acidemias

Methylmalonic academia Propionic academia Isovaleric academia Glutaric aciduria type II

Mitochondrial encephalomyopathies MERRF MERRF/MELAS overlap syndrome Kearns-Sayre syndrome

Fabry disease (a-galactosidase-A deficiency)

Subacute necrotizing encephalomyelopathy (Leigh disease)

Sulfite oxide deficiency

11-b-ketoreductase deficiency

17-a-hydroxylase deficiency

Purine nucleoside phosphorylase deficiency

Ornithine transcarbamylase deficiency

Neurofibromatosis type 1

HERNS

MERRF indicates myoclonic epilepsy with ragged-red fibers; HERNS, hereditary endotheliopathy with retinopathy, nephropathy, and stroke. Adapted from: Roach ES, Golomb MR, Adams R, et al. AHA Scientific Statement. Management of stroke in infants and children. Stroke 2008;39:2644-2691.

The diagnosis of stroke in children is often delayed due to the nonspecific way in which many children with acute stroke present to the ED. Seizures, irritability, and altered mental status are more common complaints in children than an abrupt focal deficit. Initial CT imaging often shows no abnormality.²⁷ MRI is the preferred imaging study for evaluation of stroke.

Supportive care is appropriate in most children with stroke. Interventions include:

• Maintaining a patent airway, breathing, and circulation (ABCs)
• Cardiac monitoring to evaluate for dysrhythmias predisposing to stroke such as atrial fibrillation
• Maintaining normal blood glucose and oxygenation
• Avoiding extremes of blood pressure

Thrombolysis with rt-PA is not approved for use in children under 18 years of age, and currently it is not recommended outside of research trials for children younger than 15. There was no consensus about the use of rt-PA in adolescents between 15-17 years of age.²⁸

Stroke in Children with Sickle Cell Disease

For children with sickle cell disease, exchange transfusion to reduce HbS to 30% or less is employed along with supportive care. Early consultation with critical care, hematology and neurology is crucial.

Class I Recommendations 1. Acute management of ischemic stroke resulting from SCD should include optimal hydration, correction of hypoxemia, and correction of systemic hypotension (Class I, Level of Evidence C). 2. Periodic transfusions to reduce the percentage of sickle hemoglobin are effective for reducing the risk of stroke in children 2 to 16 years of age with an abnormal TCD resulting from SCD and are recommended (Class I, Level of Evidence A). 3. Children with SCD and a confirmed cerebral infarction should be placed on a regular program of red cell transfusion in conjunction with measures to prevent iron overload (Class I, Level of Evidence B). 4. Reducing the percentage of sickle hemoglobin with transfusions before performing CA is indicated in an individual with SCD (Class I, Level of Evidence C).

Class II Recommendations 1. For acute cerebral infarction, exchange transfusion designed to reduce sickle hemoglobin to 30% total hemoglobin is reasonable (Class IIa, Level of Evidence C). 2. In children with SCD and an ICH, it is reasonable to evaluate for a structural vascular lesion (Class IIa, Level of Evidence B). 3. In children with SCD, it is reasonable to repeat a normal TCD annually and to repeat an abnormal study in 1 month (Class IIa, Level of Evidence B). Borderline and mildly abnormal TCD studies may be repeated in 3 to 6 months. 4. Hydroxyurea may be considered in children and young adults with SCD and stroke who cannot continue on long-term transfusion (Class IIb, Level of Evidence B). 5. Bone marrow transplantation may be considered for children with SCD (Class IIb, Level of Evidence C). 6. Surgical revascularization procedures may be considered as a last resort in children with SCD who continue to have cerebrovascular dysfunction despite optimal medical management (Class IIb, Level of Evidence C).

Children with Heart Disease

In addition to sickle cell disease, congenital or acquired heart disease is among the most common risk factors for ischemic stroke in children. As many as 25% of pediatric strokes are ischemic in pediatric patients, and not all of these children have known heart disease at the time of onset of symptoms. Repair of complex heart lesions and resection of atrial myxoma both reduce stroke risk. Children with high risk of cardiac embolism should be started on unfractionated heparin or low-molecular weight heparin while warfarin therapy is initiated, and then continued on anticoagulation for at least 1 year or until the high-risk lesion is corrected. Aspirin is a reasonable alternative to anticoagulants in children with suspected cardiac embolism and lower or unknown stroke risk. Large atrial septal defects should be corrected to reduce stroke risk.

Valvular heart disease, including infective endocarditis, can increase the risk of stroke in children and adults. Anticoagulation for prevention of stroke is not currently recommended for native valve endocarditis but may be appropriate to continue in patients with prosthetic valves.

Children with tuberous sclerosis complex are at substantially increased risk of cardiac rhabdomyomas, but this lesion does not substantially increase stroke risk and should not be treated with anticoagulation or surgery in a child who has not had a prior stroke.²⁹

Other diagnoses can mimic stroke. Migraine auras are typically visual, but can be sensory or motor. Hemiplegic migraine is focal motor weakness that occurs with a migraine headache. It can occur sporadically or as a result of a genetic mutation. The differential diagnosis of hemiplegic migraine includes stroke, transient ischemic attack, and tumor. Triptans, beta-blockers, and ergotamine derivatives are used for treatment of uncomplicated migraines, but may increase the risk of ischemia or prolonged aura in hemiplegic migraines.³⁰

NATIONAL GUIDELINE/ACADEMIC RESOURCE

Management of Stroke in Infants and Children: A Scientific Statement from a Special Writing Group of the American Heart Association Stroke Council and the Council on Cardiovascular Disease in the Young

http://stroke.ahajournals.org/content/39/9/2644.abstract

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Transverse Myelitis

Transverse myelitis is a rare inflammatory disorder of the spinal cord that causes rapid onset of weakness, abnormal sensation, and bowel or bladder dysfunction, without a compressive lesion of the spinal cord. Patients typically complain of pain, often localized to the affected region of the back. In children, the most commonly affected area is the neck. Transverse myelitis can be idiopathic or related to systemic inflammatory disease, autoimmune disease, or infection.

Inflammatory/Autoimmune Disorders Associated with Transverse Myelitis

Multiple sclerosis Ankylosing spondylitis Systemic lupus erythematosis Scleroderma Rheumatoid arthritis Antiphospholipid antibody syndrome

Infections Related to Transverse Myelitis

West Nile virus Herpes viruses Human immunodeficiency virus Lyme Mycoplasma Syphilis

Clinical Presentation

The bimodal peaks in onset are 10 to 19 years and 30 to 39 years. A preceding nonspecific fever, nausea, or muscle pain, probable prior viral infection, is common. Specific symptoms depend on the location of the inflammation, but patients will reliably have motor, sensory, and/or autonomic deficits below the level of the disease process.

Diagnostic Evaluation

Evaluation of suspected transverse myelitis includes laboratory workup and imaging. CSF is abnormal about 50% of the time, demonstrating inflammation in the form of increased protein and moderately increased lymphocytes. Absence of leukocytosis of CSF predicted a better outcome in children in one case series.³¹ MRI is the imaging test of choice in children and adolescents. The most common finding on MRI is central cord inflammation extending over three or more segments and absence of compressive lesion or trauma.

Treatment

High-dose intravenous steroids are the initial treatment of transverse myelitis. Plasma exchange is considered in patients who fail to improve with steroids. Immunosuppressive therapy may be indicated in refractory cases.³²

NATIONAL GUIDELINE/ ACADEMIC RESOURCE

Evidence-based guideline: Clinical evaluation and treatment of transverse myelitis

http://www.neurology.org/content/77/24/2128.full.pdf+html

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Acute Polyneuritis/Guillain-Barre Syndrome

Guillain-Barre syndrome (GBS) is the most common reason for acute paralyzing disease in otherwise well infants and children. Most patients have an antecedent infection; viral sources such as influenza, cytomegalovirus, Epstein-Barr virus, mycoplasma, and human immunodeficiency virus have all been associated with GBS. Vaccination has been implicated in some cases of GBS, particularly influenza vaccines. Parents and patients can be reassured that the risk of GBS from vaccination is significantly less than the risk of GBS from contracting the virus.³³

Clinical Presentation

Symptoms often begin with paresthesias in the fingers and toes, followed by motor weakness in the legs that ascends over hours to days. Young children often complain of pain in the legs and refuse to walk, while older children present with more clinical features that are typical of adult GBS.³⁴ The most feared complication of the disease is paralysis of the muscles of respiration and ventilatory failure, which occurs in 10-20% of children. Physical examination shows symmetric weakness and lost or diminished deep tendon reflexes of the legs.³⁵ Sensation remains intact. Children generally have a shorter disease course with return to baseline faster than adults.³⁶

Diagnostic Evaluation

Lumbar puncture and nerve conduction studies should be performed in all patients with suspected GBS. CSF will frequently demonstrate elevated protein levels with normal cell counts. Protein levels may initially be normal but then increase within 2 weeks of symptom onset. The CSF will have a normal white blood count in most cases. HIV-positive patients with GBS may have an elevated white blood count. MRI of the spine is used to exclude compressive lesions and transverse myelitis. Enhancement of the nerve roots is the most commonly seen abnormality on contrast-enhanced MRI.³⁷

Treatment

ED treatment is supportive, with airway management and respiratory support as the first priorities. Patients with difficulty lifting their head or arms, ineffective cough or difficulty swallowing, or very rapid onset of symptoms are at significantly increased risk of airway compromise, respiratory failure, and need for mechanical ventilation. Plasmapheresis and intravenous immune globulin are specific therapies for GBS, and children with suspected GBS should be sent to a facility with the capability of providing these services. Corticosteroid therapy has not been demonstrated to reduce mortality or disability outcomes in patients with GBS.

ACADEMIC RESOURCES

Guillain-Barré Syndrome

http://www.aafp.org/afp/2013/0201/p191.html

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Myasthenia Gravis and Infant Botulism

Myasthenia gravis (MG) is an autoimmune disease caused by antibodies to the acetylcholine receptor, resulting in inhibition of neural conduction. MG occurs in 10-20% of infants born to mothers with the condition and presents within a few hours of birth.

Infant botulism is caused by gut colonization with Clostridium botulinum spores, and accounts for about three-fourths of cases reported in the United States. The bacteria produce neurotoxin, which blocks the release of acetylcholine. This results in lethargy, hypotonia, and constipation in affected infants. Foodborne botulism is usually reported as small outbreaks related to homemade canned food. Honey can be contaminated with C. botulinum, and should not be fed to children younger than 12 months of age.³⁸

Clinical Presentation

Congenital myasthenia gravis and infantile botulism both cause generalized weakness and poor tone in newborns and young infants. Infants present hypotonic and weak, often with a poor suck and feeble cry. Sensory function is intact in both MG and botulism. Ninety percent will recover within 2 months.³⁹

Types of Botulism in Children

Infant Food-Borne Wound

Key Features of Botulism40

Absence of Fever No altered mental state Symmetric motor deficits Absence of sensory deficits Vital signs: normal blood pressure and heart rate

Management

Treatment of suspected botulism is supportive care and administration of antitoxin. The antitoxin will not reverse the symptoms already present, but does stop progression of the illness. Suspected cases should be reported to the state health department, which will contact the Centers for Disease Control and Prevention to access the antitoxin.⁴¹

ACADEMIC RESOURCES

http://www.bt.cdc.gov/agent/botulism/clinicians/

Bichat Guidelines for the clinical management of botulism and bioterrorism-related botulism. http://www.eurosurveillance.org/images/dynamic/em/v09n12/0912-236.pdf

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Periodic Paralysis

Familial periodic paralysis is a group of genetic diseases associated with abnormal sodium or calcium channels. The abnormality leads to either high or low serum potassium levels, resulting in muscle weakness. Between episodes, the patient has normal muscular function. Weakness is generalized and the muscles of respiration are not significantly affected. Common triggers include cold, heat, not eating, excitement, and stress. Treatment includes supportive care and correction of the electrolyte disorder.⁴² Hyperkalemic periodic paralysis generally presents in early childhood. Hypokalemic periodic paralysis starts in adolescence.⁴³

Weakness/Flaccid Paralysis in Children

Ascending Weakness/Flaccid Paralysis	Descending Weakness/Flaccid Paralysis
Guillain-Barre Syndrome Tick paralysis	Botulism Myasthenia Gravis

Acute Cerebellar Ataxia

Acute cerebellar ataxia accounts for 30-50% of all cases of ataxia in children and is frequently a post-infectious disorder in previously healthy children. Most patients are younger than 6 years of age. Varicella, coxsackie virus, and influenza are the most common viral causes, but multiple other viral etiologies have been identified.

Etiologic Agents of Acute Post-Infectious Cerebellar Ataxia

• Varicella
• Coxsackie virus
• Enterovirus
• Echovirus
• Human Herpes Virus 6
• Measles
• Mumps
• Parvovirus B19
• Epstein-Barr Virus
• Influenza

Clinical Presentation

Acute ataxia in children present most commonly as refusal to walk or gait disturbance, but some patients manifest nystagmus, speech difficulties, loss of fine motor control, or tremors. Acute cerebellar ataxia occurs suddenly, within 2 to 3 weeks of a prodromal illness.

Diagnostic Evaluation

Acute cerebellar ataxia is a diagnosis of exclusion. A child with new-onset acute ataxia and a history of recent head or neck trauma should emergently undergo CT scanning to exclude stroke, intracranial hemorrhage, or vascular injury. A child with presence of a focal neurologic exam or signs of increased intracranial pressure mandates prompt brain imaging also. Children with ataxia who have an associated fever, meningismus, and an altered mental status should undergo lumbar puncture. Lumbar puncture is unlikely to be diagnostic in children with acute-onset ataxia who present without at least one of these signs.⁴⁴ Toxicology screening and blood alcohol testing is helpful to rule out acute intoxication.

Brain imaging in children with acute cerebellar ataxia , no focal neurologic abnormalities, or signs of meningitis is not required.

Treatment

Most symptoms resolve within 2 to 3 weeks of onset. No specific treatment beyond supportive care has been shown to be better than placebo in randomized, controlled trials.⁴⁵ Prognosis is very good, with only 10% of children having long-term neurologic problems. Older children and those with Epstein-Barr viral infection have poorer outcomes.⁴⁶

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Vestibular Neuritis and Labyrinthitis

Vestibular neuritis is characterized by gait instability associated with vertigo, nausea, and vomiting, and is thought to be a post-viral inflammatory disease of the eighth cranial nerve. Nystagmus is typically present on exam, but focal weakness or sensory loss is not present. In vestibular neuritis, hearing is unaffected, while in labyrinthitis unilateral hearing loss is present.

Diagnostic Evaluation

The differential diagnosis includes cerebellar and brainstem stroke, so in patients with atypical symptoms of headache or focal neurologic signs, MRI imaging should be performed. Vestibular neuritis is diagnosed using the following clinical criteria:

• Vertigo, usually of sudden onset
• Absence of tinnitus or deafness
• Absence of focal neurological signs⁴⁷

Treatment

Treatment with corticosteroids has been shown to improve symptoms, but antivirals have not.⁴⁸

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Sydenham Chorea

Most movement disorders in children are progressive, chronic disease processes, but some inflammatory and toxic conditions present with a sudden, acute onset. Chorea is described as hyperkinetic “dancing” gestures of the hands and feet. Chorea is one of the major criteria of acute rheumatic fever and is described as “hypotonic and hyperkinetic.” Sydenham chorea is most common in children aged 5-15 years, and develops weeks to months after a group A beta-hemolytic streptococcal infection. It starts gradually, with progressive clumsiness, until the abnormal movements become more prominent. Emotional lability and dysarthria develop as the movement disorder progresses. The classic presentation of Sydenham chorea includes:

• Rapid, uncoordinated movements of feet, face, hands
• Behavior changes
• Dysarthria
• Gait disturbance
• Loss of fine and gross motor control, hypotonia
• Tongue fasiculations (“bag of worms”)
• “Milk sign” – a grip with alternately increased and decreased tension, as if milking an animal

PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) syndrome is distinguished from Sydenham chorea by onset days to weeks after streptococcal infection and presence of a tic rather than severe motor dysfunction

Diagnostic Evaluation

Most children (75%) have positive anti-streptolysin O titers. Most children will have negative throat cultures. Brain imaging is nonspecific.

Treatment

Treatment is symptomatic and usually accomplished with valproate or carbamazepine.⁴⁹ A 10-day course of penicillin at the time of diagnosis with long-term penicillin prophylaxis is appropriate to eradicate the streptococcal infection and carrier state.

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Optic Neuritis

Optic neuritis is an inflammation of the optic nerve and may be related to different systemic conditions. The clinical presentation of this pathology usually includes sudden loss of visual acuity that may be unilateral or bilateral, visual field deficits, pain with eye movements, dyschromatopsia, a relative afferent pupillary defect, and optic disk swelling. Adults usually present with monocular loss of vision, while children more frequently complain of bilateral, more severe symptoms. Optic neuritis most commonly occurs after a viral infection (measles, mumps, chicken pox, pertussis, infectious mononucleosis, and immunizations) and may be the result of a biotinidase deficiency.

Diagnostic Evaluation

MRI imaging of the brain should be performed to evaluate for lesions indicating a high risk of developing multiple sclerosis.

Treatment

Intravenous methylprednisolone can shorten the duration of visual loss but does not reduce the risk of long-term vision loss. Interferon treatment may also be indicated to reduce the risk of multiple sclerosis in patients with an acute optic neuritis event at high risk of developing the disease.⁵⁰

NATIONAL GUIDELINE/ACADEMIC RESOURCE

Optic neuritis in pediatric population: A review in current tendencies of diagnosis and management

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4087179

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Facial Nerve Palsy

Facial nerve palsy in children can be central or peripheral. Sparing of the forehead muscles suggests a central cause of weakness and should be followed up with emergent brain imaging. Children with a peripheral facial nerve palsy (i.e., Bell’s palsy) present with acute unilateral paralysis of the face. The forehead sags, the eyelid will not completely close, and the mouth draws to the unaffected side. Lyme disease and otitis media may precipitate a peripheral facial palsy. In endemic areas, Lyme is a more frequent cause of facial weakness than otitis media.⁵¹

Treatment of the facial palsy depends on the underlying cause of the weakness. The American Academy of Neurology recommends treatment of Bell’s palsy with glucocorticoids.⁵² The largest trials have not shown a significant benefit to antiviral therapy.⁵³

Causes of Facial Nerve Palsy

Congenital – Moebius Syndrome Neoplastic Trauma Idiopathic — > 50% of cases

Neurodegenerative Disease

Neurodegenerative disease in children is rare and comes in many forms. The key factor in neurodegenerative disease is regression and deterioration of neurologic function, with loss of speech, motor function, hearing, vision, and/or cognition.

Children with previously undiagnosed disease may present to the ED with altered mental status, failure to thrive, developmental delays, or recurrent vomiting. Physical exam findings may include large or small head size, liver enlargement, abnormal tone, feeding, or growth abnormalities. Primitive reflexes or abnormal movements may be seen. Seizures are common in children with neurodegenerative disease. The differential diagnosis includes sepsis, toxic exposure, meningitis, encephalitis, trauma, or intracranial tumor.⁵⁴

Table: Neurodegenerative Diseases

Disease Process	Age at Onset	Manifestations	Complications and Prognosis
Adrenoleukodystrophy55	4-8 years	Spasticity Strabismus Aphasia Hyperactivity Hearing loss Seizures	Progression to coma about 2 years after neurologic symptoms develop Death within 10 years of onset
Metachromatic Leukodystrophy56	3 Forms: Late infantile (1-2 years) Juvenile (4-12 years) Adult (> 12 years)	Hyper- or hypotonia Intellectual disability/ cognitive regression Seizures Incontinence Frequent falls Optic atrophy	Life span is determined by age of onset
Tay-Sachs	Early infancy	Hypersensitivity to noise Increased startle response Myoclonic seizures Cherry-red spot - macula	Death by 2 years of age
Niemann-Pick	5 different types: Type C, 2-4 years D: later childhood	“Foam cells” in liver and bone marrow Macular degeneration Cognitive regression Hepatosplenomegaly Hypotonia, areflexia 25% cherry-red spot	Types A, C,D progress to death within 2-5 years
Multiple Sclerosis57	Onset before age 18 in 5% of patients	Fatigue, depression Cognitive disability Episodic flares – vision loss, seizures, ataxia May present with optic neuritis, transverse myelitis, or brainstem syndrome	Over time, accumulated disability Cognitive decline faster in children over time than adults
Neuromyelitis Optica (Devic Disease)58	Median age is 32-41 years but some reported cases in children	CNS demyelination Optic neuritis and transverse myelitis	Can be relapsing and remitting; can lead to death

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Immunodeficiencies

Children with primary immunodeficiencies can manifest neurologic symptoms as a consequence of infection and malignancies of the central nervous system, or as a result of the disease process itself. There are more than 150 described disorders, and overall the incidence is 1 in 2000 children.

Table: Immunodeficiencies

Disorder	Symptoms	Infections	Other Manifestations
Severe Combined Immune Deficiency (SCID)59	In adenosine deaminase type: intellectual disability Hearing and visual impairment Hypotonia Movement disorders	Persistent candidiasis Severe viral infections	Absent thymic shadow on Chest radiography Lymphopenia (ALC < 2500) Recurrent fevers Failure to thrive Chronic diarrhea
Wiskott-Aldrich	Thrombocytopenia and bleeding diathesis present at birth	Opportunistic infections Severe, difficult to treat ear infections, meningitis, pneumonia	Eczema Lymphadenopathy Hepatosplenomegaly Leukemia and B-cell lymphoma
DiGeorge Syndrome60	Seizures Schizophrenia Most common cause of mental retardation due to genetic deletion syndrome	Variable severity, generally upper and lower respiratory tract	Heart anomalies Hypoplastic thymus Hypocalcemia Developmental delay Cleft palate
Hyperimmunoglobulinemia E (Job Syndrome)	CNS vasculitis Cerebral arterial stenosis and abnormalities	Recurrent staphylococcal boils Recurrent otitis media and sinus infections	Hyperextensible joints Eczema Recurrent fractures Coarse facies

Management in the ED of acute illness is supportive, with infection-specific antibiotic treatment initiated early. For undifferentiated infection or suspected sepsis, broad-spectrum antibiotics are indicated. Infants with facial stigmata of primary immunodeficiency may be detected in the newborn nursery, while less apparent cases may go undetected for years. Hematopoietic stem cell transplantation provides immune reconstitution and may be indicated for severe forms of SCID, Wiscott-Aldrich syndrome, and other T-cell defects.⁶¹ Immune globulin may be administered subcutaneously, intramuscularly, or intravenously.⁶²

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