Febrile Seizure

A boy presents to the ER with a generalized tonic-clonic seizure. He had a day of URI symptoms and a fever of 103 degrees the day of the seizure.

What else do you want to know in order to decide how to manage this patient?

The boy's age, the length of the seizure, and the type of seizure.

This patient has had a seizure, probably provoked by fever. Febrile seizures most commonly occur between the ages of 6 months and 5 years. They are divided in "simple" and "complex" categories:

If the patient is 2 years old, had a 10 minute generalized tonic-clonic seizure, and is otherwise a neurologically normal child, does this patient need further evaluation, and how might he be managed?

This is a simple febrile seizure. Consider LP only if there is clinical suspicion for meningitis. According to the AAP, there is no need to perform an EEG, CT scan, or labs. Though the major risk is recurrence (30%), risk of developing epilepsy is low and there is no evidence to indicate that antiepileptic drugs (AEDs) prevent the development of epilepsy. So AEDs are not recommended as the risks of those medications outweigh the benefits. However, depending on parental comfort, AEDs may in some cases be appropriate.

Resources

Frequent Falls

A 4 year old boy presents to his pediatrician because he seems to fall more than his peers. The parents believe he trips over his feet when he runs. They first noticed this at 3 years of age, and the patient's pediatrician reassured the parents that this was normal. However, the patient continues to have falls, and is not able to keep up with his peers, though he is continuing to make improvements in his motor skills. Developmentally, he reached his early milestones on time, and walked at 15 months. Language development and fine motor skills are normal.

What one test would you order ?

Serum creatine kinase (CK) is typically elevated to 50-100 times normal in patients with Duchenne muscular dystrophy (DMD), and may be increased as early as the newborn period. The negative predictive value is high, that is, if the CK is normal this is very unlikely to be DMD.

If abnormal, what would your next step be?

DMD and Becker muscular dystrophy are X-linked "dystrophinopathies," caused by mutations in the dystrophin gene, which encodes for a membrane protein. You would order a genetic test for mutation in the dystrophin gene.

What would an EMG and muscle biopsy show in DMD?

An EMG would show myopathic changes with small polyphasic potentials. Variations in muscle fiber size, necrotic muscle fibers, increased numbers of intracellular nuclei, and increased connective tissue (see below). Immunoblotting would show absence or near-absence of the dystrophin protein.

What physical exam findings do you see with DMD?

Pateints with DMD develop pseudohypertrophy, most commonly of the calf (see below), from hypertrophy of remaining muscle fibers and infiltration with connective and adipose tissue. On palpation, their calfs are described as having a "woody feel."

Patients are hyporeflexic and weak, particularly in the proximal lower extremities, and this is particularly noticeable on a functional exam. The characteristic finding is "Gower's sign" (see image below): when going from a seat to a stand, the patient must use his arms to push off his legs in order to extend his knees and lift his trunk. Patients also tend to have a waddling gait, difficulty running, and lordosis.

Click on image above to see video of Gower's sign

Are there any treatment options?

A 2004 Cochrane review showed that steroids improve muscle strength and function in the short term (up to two years). Steroids are typically started around the age of 7 years. However, the prognosis is still poor. Though patients may experience improvement until 6 years of age, they subsequently have progressively deteriorating course. In addition to weakness, patients with DMD develop dilated cardiomyopathy and conduction abnormalities, scoliosis, and respiratory failure. Most patients are in a wheel chair by the age of 12, and die in their late teens or early twenties

Resources

Poor attention

8 year old girl presents to her pediatrician with worsening school performance due to poor attention. On further questioning, she seems to "space out" when she's in class.

What diagnosis are you suspicious of? What else do you want to know about the "spacing out" spells?

These episodes are suspicious for absence seizures. In order to help you make this diagnosis, you should ask if the episodes can be interrupted, if the patient has any abnormal movements during the spells, and if she only has these spells during school, or does she also have them at home and when she's doing activities she enjoys.

It is important to know if the spells can be interrupted. Many kids have staring spells, and the majority are not seizures. However, it is sometimes difficult to interrupt benign "spacing out" by calling the child's name. Parents should be instructed to touch the patient during the episode; this is much more likely to interrupt a benign spell but will not interrupt a seizure. Commonly with absence seizures, the patient will have mouth movements or eye fluttering, and this may make it difficult to differentiate these seizures from complex partial seizures. Also, bored kids will have staring spells in school, but will not have this problem when doing something that interests them. Absence seizures occur even during interesting activities (e.g. video game playing).

Is this seizure type focal or generalized?

Generalized

What is the characteristic EEG pattern seen with this type of seizure?

Three hertz (three per second) spike and slow wave complexes:

How might you induce a seizure in the clinic?

Hyperventilation

What AEDs would you choose, and which would you not choose?

Absence seizures can be treated with ethosuximibe (Zarontin), lamotrigine (Lamictal), Valproic acid, or clonazepam. You would not choose an AED used for partial seizures such as carbamazepine (Tegretol) or oxcarbamazepine (Trileptal), medications which can signicantly worsen these generalized seizures.

What epilepsy syndromes are characterized by absence seizures?

Childhood absence epilepsy (good prognosis, absences usually resolve)
Juvenile absence epilepsy (absences and generalized tonic clonic seizures)
Juvenile myoclonic epilepsy (lifelong seizures)
Epilepsy with myoclonic absences (absence seizures accompanied by myoclonus)
Lennox-Gastaut syndrome (catastrophic epilepsy with many seizure types)

Weakness

A previously well, 4 year old boy presents to the ER with worsening bilateral lower extremity weakness. He had been well up until 5 days ago, when he was noted to be favoring one leg. He was also noted to have a fever and a cough not long before his symptoms began. His gait difficulties got progressively worse, and seemed to also involve his other leg, to the point where he could no longer walk. He also seems to not using his arms as much, and cannot actually sit up straight without support. The parents believe his speech is less clear than usual, and he seems sleepy.

Approach weakness by thinking about the differential diagnosis based on location. What part of the nervous system is the "lesion" most likely located (muscle, neuromuscular junction, peripheral nerve, anterior horn cell, spinal cord, brain stem, cortex)? What further information would you need to better localize it?

The patient appears to have mental status changes. This points to a cortical or subcortical lesion. You would want to know if the patient has any bulbar signs which would also point towards a lesion above the spinal cord. The physical exam is also an important key to localization.

Describe the characteristic physical exam findings with an upper motor neuron (UMN) lesion vs. a lower motor neuron (LMN) lesion.

Does a flaccid paralysis rule out an upper motor neuron lesion?

Nope. Soon after an upper motor neuron insult the patient may be flaccid, and this may, over time, progress to a spastic paralysis.

The patient's exam shows altered mental status, normal fundoscopic exam, bilateral facial weakness and a weak voice, weakness in both legs, left greater than right, and weakness, though less pronounced in the upper extremities. He is hyperreflexic throughout with crossed adductor response and clonus in both ankles. Babinksi is present bilaterally. Sensation is hard to assess, but seems grossly intact. What's on your differential diagnosis?

These are characteristic upper motor neuron findings, and with the bulbar involvement and encephalopathy, point towards a cortical or subcortical lesion. You might consider:

Infectious: Encephalitis is an important consideration and is supported by the history of fever and altered mental status. Also consider abscess and tuberculosis.
Inflammatory: Guillain barre syndrome and ADEM (acute disseminated encephalomyelitis) are both post-infectious, inflammatory causes of weakness. Patients with Guillain barre syndrome have absent reflexes, and altered mental status is not characteristic as this syndrome affects nerve roots. Multiple sclerosis, though unusual at this age, is also possible.
Vascular: Stroke, vasculitis, and cerebral venous sinus thrombosis are all possible, if less likely etiologies.
Toxic/Metabolic
Neoplastic: Given the acute onset, neoplastic causes are unlikely, however GBM or CNS lymphoma are considerations.

What are your next diagnostic steps?

Of primary importance is treating and ruling out an infectious process. You would do a CT scan to look for gross lesions or bleeds and to look for any contraindication for LP, then lumbar puncture, and start empiric antibiotics. MRI will also likely be needed.

The LP shows: WBC 9, RBC 2, glucose 55, protein 60, gram stain: no organisms

MRI (axial T2-weighted):
Note that the lesions below do not enhance with contrast.

What is the most likely diagnosis?

ADEM (acute disseminated encephalomyelitis): an inflammatory, demyelinating disorder, primarily of children, typically occurs after an infection (often a URI) or vaccination. It often presents as encephalopathy and multifocal neurologic deficits. An LP may show a mild leukocytosis and elevated protein (as in this case), but may be normal. MRI is key to the diagnosis and shows subcortical white matter hyperintensity on T2, with basal ganglia, brainstem, and spinal cord also commonly affected. Enhancement is unusual and suggestive of infection. Accepted treatment is with high dose steroids, followed by an oral taper. Other experimental immunosuppresive therapies have been tried. Prognosis is generally good, with 60-90% having a complete recovery. Traditionally considered monophasic in nature, multiple episodes are often reclassified as multiple sclerosis.

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Colic

A 6 month old boy presents with colic. For the last few months he has been having episodes of crying, and to his parents, what seems like abdominal pain. He stiffens his arms and legs and bends forward, as if in pain. It tends to happen after he wakes up. And can sometimes happen multiple times in a row. His birth was unremarkable, and developmental milestones have been reached. This is the parents' first child. Exam is only notable for a light colored birthmark on the patient's back.

Are you concerned or reassured?

Colic is a common complaint and in most cases parents can be reassured. However, there are aspects of the description that should concern you. The tonic stiffening and "bending forward," clustering, and occuring upon arousal are characteristic features of infantile spasms (see resources for videos). A low threshold should be used for referral to neurology.

What further evaluation should be done?

The first step should be an EEG.

What is the characteristic finding on EEG in patients with infantile spasms?

Hypsarrythmia: high voltage, slow spikes and waves in all cortical areas (see below). The infantile spasms are marked by an electrodecrement on EEG, where there is a decrease in voltage.

What is West Syndrome?

West Syndrome is defined as the triad of infantile spasms, hypsarrhythmia, and arrest of psychomotor development.

What further evaluation needs to be done?

A search for the etiology is warranted given that infantile spasms, in the vast majority of cases, are found to be symptomatic (i.e. caused by a known, underlying lesion). The most common cause is a prenatal event, such as cortical dysplasia (30%), holoprosencephaly, lissencephaly, and chromosomal anomalies (15%) such as Down's syndrome. Other causes include neurocutaneous disorders, most commonly Tuberous Sclerosis (10-30% of prenatal causes). The patient's light colored birth mark is suggestive of this diagnosis. Of note, infantile spasms occur in about 70% of patients with tuberous sclerosis. Infantile spasms may also result from inborn errors of metabolism such as PKU, Menkes disease, Leigh syndrome and urea cycle disorders. Other etiologies include perinatal causes such as PVL, and postnatal causes such as infectious or hypoxic-ischemic events. An MRI should be obtained, and a metabolic work-up considered.

What treatment options are available?

The first line of treatment is commonly corticotropin (ACTH). Other accepted AED options include vigabatrin, valproic acid, topamax and zonisamide. Non-medication options include the ketogenic diet, vagus nerve stimulator, and surgery. Despite treatment, the disease course is poor with more than half of patients developing other seizure types, often resistant to treatment, 20-50% developing Lennox-Gastaut syndrome, up to 90% developing moderate to severe learning difficulties, and mortality as high as 30%.

Resources (articles and videos)

Facial asymmetry

You are consulted on a DOL 3, ex-term boy in the well-baby nursery for facial asymmetry. Though the boy's face looked fine most of the time, when he cried it appeared as though the right side of his mouth was drooping. The upper face appears symmetric.

What other questions do you have?

What kind of delivery was this? Are there any other neurologic deficits?

What is the most likely diagnosis? Which side of the face is affected?

Asymmetric crying facies, i.e. congenital hypoplasia of the depressor anguli orsi muscle. Although it appears that the right side of the mouth is drooping when the baby cries, in fact, the asymmetry results from failure to depress the left side of the mouth, so the left side is affected.

What else is on your differential diagnosis?

Facial nerve injury from forceps delivery, Mobius syndrome (congenital underdevelopment of CNs VII, VI and sometimes others, typically bilaterally, may be associated with other anomalies).

Is there any further work-up? What is the prognosis?

Though asymmetric crying facies is usually isolated, it can be associated with renal, cardiac or other congenital defects. Though the deficit does not resolve, the patient's other facial muscles will develop to compensate for the hypoplasia so that the asymmetry will become less noticable with time.

Droopy eyelid

You are consulted on a 5 year old boy who woke up yesterday morning with a droopy eyelid. The parents noticed that he wasn't opening his right eye as well as his left. Later in the day, looking closer, they saw that his pupils seemed unequal. Although he was generally an energetic, healthy boy, since the night before last he has not had been eating well and has not been as active as usual. On exam, his right eye is more constricted than his left, and this is more evident when there is less ambient light. His pupils are reactive, his extra-ocular movements are intact, and he does not have any other facial asymetry or motor or sensory deficits, and reflexes are normal.

Which pupil do you think is larger? What diagnosis are you suspicious of?

The left pupil. The anisocoria, with the ptosis in the absence of other cranial nerve deficits, suggests Horner's syndrome. That the anisocoria is more evident in darkness suggests that the right eye is failing to dilate, rather than the left eye failing to constrict. Horner's syndrome is an interruption of the sympathetic fibers supplying the face. The characteristic features are ptosis, miosis, and anhydrosis on the side of the lesion. In the image below, this cat, who developed Horner's syndrome after sympathetic fibers were damaged in an operation to remove a nasopharyngeal polyp (he agreed to have his picture used for educational purposes), has left eye ptosis and miosis.

Why do you get ptosis with Horner's syndrome if cranial nerve III is not involved?

Ptosis is a typical feature of cranial nerve III deficits, as CN III supplies the levator palpebrae superioris. However the sympathetic fibers also supply a muscle that assists with eye opening, the muscle of Mueller, which explains the ptosis in this syndrome.

Describe the pathway the sympathetic fibers take to reach the face.

Beginning at the hypothalamus, the first order neuron descends through the brain stem to reach the thorac cord, where they synapse on the preganglionic neurons (2nd order). These fibers leave the cord, travel to the sympathetic chain, then synapse on the postganglionic (3rd order) neuron at the cervical ganglion. The third order neuron travels along the carotid, through the cavernous sinus, to reach the eye and sweat glands of the ipsilateral face.

Describe lesions affecting the first, second and third order neurons that could result in Horner's syndrome.

First order neuron:
Brainstem stroke (Wallenburg, aka Lateral Medullary Syndrome)
Brainstem mass
Syringomyelia
Multiple sclerosis

Second order neuron:
Pancoast tumor (tumor of the apex of the lung)
Neuroblastoma
Brachial plexus injury
Sarcoidosis
Post-traumatic, post-surgical

Third order neuron:
Carotid dissection
AVM
Migraine
Orbital pseudotumor
Tolosa-hunt syndrome

Which of the above options is most likely given the patient's history and exam findings?

Given that there are no other cranial nerve deficits or symptoms referrable to the spinal cord, a lesion of the first order neuron is less likely. The second-order neuron is a possibility, with neuroblastoma the most likely possibility. About 2% of neuroblastomas present with Horner's syndrome, and in one study including 18 children with Horner's syndrome who underwent complete imaging, 22% were found to have neuroblastoma (resources). A carotid dissection or AVM, though unlikely, should be ruled out. Should complete imaging reveal no tumor or vascular lesion, a migraine, a diagnosis suggested by the patient's malaise, should be considered.

Resources

First Seizure

8 year old girl is brought to the ER seizing. In your brief history you learn that he has been seizing for about 15 minutes.

What should you give to stop the seizure?