Neurology Flashcards
1
Q
What is hypotonia?
How is this different from weakness?
A
- Decreased resistance of movement during passive stretching of muscles
- Weakness is the decreased or less than normal force generated by the active contraction of muscles
2
Q
Central vs. Peripheral Hypotonia
A
-
Central hypotonia
- Dysfunction of the upper motor neurons
- Cortical pyramidal neurons & their descending corticospinal pathways
-
Peripheral hypotonia
- Dysfunction of the lower motor neurons
- Spinal motor neurons & distally to muscle fibers
3
Q
History in a hypotonic infant may reveal….
A
- Antenatal or neonatal problems
- Peripheral hypotonia: decreased fetal movements & breech presentation
- Central hypotonia: seizures in the neonatal period
4
Q
What are the physical exam findings in hypotonia?
A
- Weak cry, decreased spontaneous movement, frog-leg posture, muscle contractures
-
Central hypotonia
- Altered level of consciousness
- Decreased DTRs, ankle clonus
-
Peripheral hypotonia
- Consciousness unaffected
- Muscle bulk & DTRs decreased
-
Congenital neuromuscular disorder pts
- Bilateral ptosis, ophthalmoplegia, flat mid-face, fish-shaped mouth, high-arched palate, chest wall abnormalities (bell-shaped chest, pectus excavatum, carinatum), bilateral cryptorchidism
5
Q
What is the etiology of hypotonia?
A
- Systemic pathology
- Sepsis, electrolyte abnormalities, hepatic or renal encephalopathy
- Neural pathology
6
Q
What is the differential diagnosis of central hypotonia?
A
-
Acquired
- Electrolyte abnormality
- Hypoxic-ischemic injury
- Infection
- Sepsis vs. Meningitis
- Intracranial hemorrhage
- Trauma (cerebral, cervical)
-
Congenital
- Cerebral malformation
- Chromosomal disorder
- Down syndrome
- Prader-Willi syndrome
- Metabolic disorder
- Urea cycle defects
7
Q
What is the differential diagnosis of peripheral hypotonia?
A
-
Spinal cord
- Spinal muscular atrophy
-
Peripheral nerves
- Familial dysautonomia
-
Neuromuscular junction
- Botulism
- Neonatal myasthenia
- Magnesium toxicity
-
Muscle
- Congenital muscular dystrophy
- Congenital myotonic dystrophy
- Metabolic myopathy
- Pompe’s disease
- Phosphofructokinase deficiency
- Structural myopathy
- Central core disease
- Nemaline rod myopathy
8
Q
When evaluating hypotonia, _______________ must be ruled out.
A
- acute life-threatening causes
- sepsis, meningitis, acute metabolic disorder
9
Q
When central hypotonia is suspected, what 3 things need to be done?
A
-
Head CT scan
- Rule out acute CNS injury or congenital malformation
-
Serum electrolytes
- Ca, Mg, ammonia, lactate, pyruvate
- Rule out metabolic disorders
-
High-resolution chromosome studies
- FISH tests for suspected genetic disorders
- ex: Prader-Willi syndrome
10
Q
When peripheral hypotonia is suspected, what 4 things need to be done?
A
- Serum creatinine kinase (CK) levels
- DNA tests for spinal muscular atrophy
- EMG: nerve conduction studies crucial to identify myasthenic disorders
- Muscle biopsy
11
Q
Spinal muscular atrophy (SMA)
- definition
- epidemiology
A
- Anterior horn cell degeneration
- Hypotonia, weakness, tongue fasciculations
- 1 in 10,000-25,000 live births
- 2nd most common hereditary neuromuscular disorder after Duchenne’s
12
Q
What is the classification system for spinal muscular atrophy?
A
-
Type I
- Infantile form
- Onset <6 mo
- Werdnig-Hoffman disease
-
Type II
- Intermediate form
- 6-12 mo
-
Type III
- Juvenile form
- >3 YO
13
Q
What is the etiology of spinal muscular atrophy?
A
- Autosomal recessive
- Mutations in survival motor neuron gene (SMN1) on chromosome 5
- Pathology of spinal cord
- Degeneration & loss of anterior horn neurons
- Infiltration of microglia & astrocytes
14
Q
What are the clinical features of spinal muscular atrophy?
A
-
Weak cry, tongue fasciculations
- Difficulty sucking & swallowing
- Bell-shaped chest
-
Frog-leg posture when in supine position
- Generalized hypotonia, weakness, areflexia
- Normal extraocular movements & normal sensory exam
15
Q
How is spinal muscular atrophy diagnosed?
A
-
DNA testing
- Diagnostic >90% of cases
-
Muscle biopsy
- Atrophy of groups of muscle fibers that were innervated by damaged axons
16
Q
What is the management & prognosis of spinal muscular atrophy?
A
-
Treatment is supportive
- Gastrostomy tube feeding
- Diligent surveillance & therapy of respiratory infections
- Physical therapy to maintain ROM
- No cure
-
Prognosis
- SMA type I: survival >1 YO unusual
- Death: respiratory insufficiency or pneumonia
- SMA types II & III: survival until adolescence & adulthood
- SMA type I: survival >1 YO unusual
17
Q
What is the definition of infantile botulism?
What is the etiology?
A
- Bulbar weakness & paralysis during 1st yr
- Secondary to ingestion of Clostridium botulinum species & absorption of botulism toxin
- Source
- Infected foods: honey, spores
- Toxin prevents presynaptic release of ACh
18
Q
What are the clinical features of infantile botulism?
A
- Onset of symptoms 12-48 hrs after ingestion
- Classic first symptom: constipation
-
Neurologic symptoms
- Weak cry & suck
- Loss of previously obtained motor milestones
- Opthalmoplegia, hyporeflexia
-
Paralysis: symmetric & descending
- Diaphragmatic paralysis can occur
19
Q
How is infantile botulism diagnosed?
A
- Suggestive hx, neuro exam, toxin in stool
-
EMG: brief, small-amplitude muscle potentials
- Incremental response during high-frequency stimulation
20
Q
How is infantile botulism managed?
A
- Treatment is supportive
- Nasogastric feeding
- Assisted ventilation
- Botulism immune globulin
- Antibiotics CONTRAINDICATED
21
Q
What is congenital myotonic dystrophy?
What is the epidemiology?
A
- Myotonia: inability to relax contracted muscles
- Autosomal dominant muscle disorder
- Presents in newborn period
- Weakness & hypotonia
- 1 in 30,000 live births
22
Q
What is the etiology of congenital myotonic dystrophy?
A
- Trinucleotide repeat disorder
- Autosomal dominant, variable penetrance
- Chromosome 19
- Transmission through infected mothers (>90%)
- Earlier onset in mother, more likely will transfer
23
Q
Congential myotonic dystrophy
- antenatal hx
- neonatal hx
- physical exam
- adulthood
- additional problems
A
- Antenatal hx
- Polyhydramnios: poor swalling in utero & decreased fetal movements
- Neonatal hx
- Feeding & respiratory problems
- Physical exam
- Facial diplegia (bilateral weakness), hypotonia, areflexia, arthrogryposis (multiple joint contractures)
- Myotonia not always present in newborn
- Later, by 5 YO
- Adulthood
- Myotonic facies (atrophy of masseter & temporalis muscles), ptosis, stiff straight smile, inability to release grip after hand shaking (myotonia)
- Additonal problems
- Mental retardation, cataracts, cardiac arrhythmias, infertility
24
Q
How is congenital myotonic dystrophy diagnosed?
A
- Should be suspected in all infants w/ hypotonia
- Mother should also be examined
- DNA testing
- EMG & muscle biopsy no longer indicated
25
**Congential Myotonic Dystrophy**
management
prognosis
* **Treatment is supportive**
* Infants may require assisted ventilation & gastrostomy tube feedings
* Outlook is guarded
* Infant mortality up to 40% (resp problems)
* **All survivors have mental retardation**
* Average IQ 50-65
* Feeding problems subside w/ time
26
What is **Hydrocephalus**?
* Increased CSF under pressure w/i ventricles
* Results from:
* Blockage of CSF flow
* Decreased CSF absorption
* Increased CSF production (rare)
27
What are the 3 types of hydrocephalus?
* **Noncommunicating hydrocephalus**
* Enlarged ventricles
* Obstruction of CSF flow through ventricles
* ex: aqueductal stenosis
* **Communicating hydrocephalus**
* Enlarged ventricles
* Increased production of CSF (tumors)
* Decreased absorption of CSF (bacterial meningitis)
* **Hydrocephalus ex vacuo**
* ****Ventricular enlargement caused by brain atrophy
*
28
What are the **congenital** causes of hydrocephalus?
* Chiari Type II malformation
* Dandy-Walker malformation
* Congenital acqueductal stenosis
29
What are the **acquired** causes of hydrocephalus?
* Intraventicular hemorrhage (preterm infants)
* Bacterial meningitis
* Brain tumors
30
What is Chiari type II malformation?
* Downward displacement of the cerebellum & medulla through the foramen magnum
* **Blocks CSF flow**
* Associated w/ lumbosacral myelomeningocele
31
What is Dandy-Walker malformation?
* Absent or hypoplastic cerebellar vermis
* Cystic enlargement of the 4th ventricle
* **Blocks flow of CSF**
32
What is Congenital Aqueductal Stenosis?
* X-linked trait
* Thumb abnormalities
* CNS abnormalities: spina bifida
33
The main clinical feature of hydrocephalus is \_\_\_\_\_.
increasing head circumference
\>97% for age
34
What are the clinical features of hydrocephalus for **infants**?
* Infants w/ open cranial sutures
* Large anterior & posterior fontanelles & split sutures
* **Sunset sign**
* Tonic downward deviation of both eyes
* Pressure from enlarged 3rd ventricles on the upward gaze center in the midbrain
35
What are the clinical features of hydrocephalus for **older children**?
* Closed cranial sutures
* **Increased ICP**
* Headache
* Nausea & vomiting
* Unilateral 6th nerve palsy
* Papilledema
* Brisk DTRs but w/ a usually downward plantar response
36
How is **hydrocephalus** evaluated & managed?
* Increasing head circumference & signs/symptoms of increased ICP
* **Urgent head CT scan**
* Surgical placement of **ventriculoperitoneal shunt**
* Divert flow of CSF
* Complications: shunt infection/obstruction
37
What is the prognosis of hydrocephalus?
* **Pts w/ aqueductal stenosis**
* Best cognitive outcome
* **Pts w/ Chiari type II malformation**
* Low-normal intelligence
* Language disorders
* **Pts w/ X-linked hydrocephalus**
* Severe mental retardation
38
What is **spina bifida**?
Any failure of bone fusion in the posterior midline of the vertebral column
39
**Definitions**
* Neural tube defects
* Myelomeningocele
* Meningocele
* SB occulta
* **Neural tube defect**
* All forms of failure of neural tube closure
* Anencephaly to sacral meningocele
* **Myelomeningocele**
* Herniation of spinal cord tissue & the meninges through a bony cleft
* Commonly the lumbosacral region
* 20X more than meningocele
* **Meningocele**
* Herniation of the meninges only
* _Not associated w/ neural deficits_
* **SB occulta**
* No herniation of tissue through vertebral cleft
40
The highest incidence of **neural tube defects** is in _______ and the lowest is in \_\_\_\_\_.
Ireland (1 in 250 live births)
Japan (1 in 3,000 live births)
41
What is the **etiology** of neural tube defects?
* Multifactorial
* Environmental
* Genetic
* Nutritional
* Teratogenic factors
* Mothers taking _folic acid_ have decreased incidence of spina bifida
* **Teratogens that cause SB**
* Valproate, phenytoin, colchicine, vincristine, azathioprine, methotrexate
42
What are the clinical features of **SB occulta**?
* Skin on the back epithelialized
* Hairy patch or dimple covers the area
* Usually lumbosacral region
* No neurologic defects
43
What are the clinical features of **Meningocele**?
* Fluctuant midline mass overlying the spine
* Filled w/ CSF, transluminated
* Neurologic deficits mild/absent
44
What are the clinical features of **Myelomeningocele**?
* Fluctuant midline mass anywhere along spine
* Commonly lumbosacral region
* **Neurologic defects present**
* Depend on level of lesion
* Complete paraplegia (above L3) to preserved ambulation & variable bladder or bowel incontinence (S3 & below)
45
What are the 5 associated abnormalities & complications of **Myelomeningocele**?
* **Hydrocephalus**
* _90% of lumbosacral_ associated w/ Chiari type II malformations & hydrocephalus
* **Cervical hydrosyringomyelia**
* Accumulation of fluid w/i the central spinal cord canal & within the cord itself
* **Defects in neuronal migration**
* Gyral anomalies
* Agenesis of corpus callosum
* **Orthopedic problems**
* Rib abnormalities, deformities of LE, LE fractures from loss of sensation
* **GU defects**
46
How is spina bifida diagnosed **prenatally**?
* **Alpha fetoprotein**
* Elevated in amniotic fluid & maternal serum
* At 16-18 wks gestation, detects 80% of spinal defects
* **Fetal sonography**
* Highly sensitive
47
How is spina bifida diagnosed **after birth**?
* **SB occulta**
* Skin abnormality overlying the spine
* Confirmed by spinal radiographs
* **Meningocele**
* Physical exam findings
* Confirmed by MRI of spinal cord & spine
* **Myelomeningocele**
* Physical exam
48
How is spina bifida managed?
* SB occulta doesn't require treatment
* Meningocele: _surgical repair_
* Myelomeningocele
* _Urgent surgical repair w/i 24 hrs of birth_
* Reduce morbidity & mortality from infection
* Prevent further trauma to exposed neural tissue
49
What is the prognosis of spina bifida?
* **SB occulta & meningocele**
* Excellent prognosis
* **Myelomeningocele**
* 90% of pts survive to adolescence
* Many handicapped
* Associated problems:
* Wheelchair dependency
* Bladder/bowel incontinence
* Mental retardation
* Seizures
* Precocious puberty
* Pressure sores
* Fractures
50
What is the definition of a **coma**?
* State of unawareness of self & environment
* Patient lies w/ eyes closed
* Unarousable by external stimuli
51
What is the etiology of a coma?
Young vs. old children?
* **Children \<5 YO**
* Nonaccidental trauma
* Near-drowning
* **Older children**
* Drug overdose
* Accidental head injury
52
What are the etiologies of **focal lesions** that lead to a coma?
Abnormal neuroimaging studies
* **Supratentorial lesions**
* Vascular: subarachnoid hemorrhage, multiple infarcts, thalamic infarct
* Trauma: subdural hematoma, nonaccidental trauma
* Tumors
* Demyelination (postinfectious encephalitis)
* **Infratentorial lesions**
* Vascular: cerebellar hemorrhage
* Trauma
* Tumors
53
What are the etiologies of **diffuse lesions** that lead to a coma?
Normal neuroimaging studies
* **Ingestion**
* Drugs: atropine, scopolamine, benzodiazepines, barbiturates, ethanol, lithium, opiates, TCAs
* Toxins: lead, mercury
* **Infection**: encephalitis
* **Hypoxemia**: near-drowning, CO
* **Abnormal metabolites**
* Metabolic: hypo/hyperglycemia, hypo/hypernatremia, thiamine deficiency
* Endocrine: hypo/hyperthyroidism, hypo/hypercortisolism
* **Organ failure**
* Cardiac arrest, hepatic failure, uremia
* **Seizures**
* Nonconvulsive status epilepticus
* **Reye syndrome**
54
What is the **goal** in the assessment of the comatose patient?
* Determine the depth of the coma
* Identify the neurologic signs that indicate the site & cause of the coma
* Monitor the patient's recovery
55
What are 6 ways to assess a comatose patient?
* Glascow Coma Scale
* Head & neck exam
* Abnormal motor responses
* Abnormal respiratory responses
* Pupillary size & reactivity
* Other brainstem reflexes
56
What is the **Head & Neck exam** for a comatose patient?
* Scalp injuries
* Breath odors (alcohol intoxication, DKA)
* Nuchal rigidity (meningitis)
* CSF or blood draining from auditory canal
* Indicates a basilar skull fracture
57
What are some **abnormal motor responses** that can indicate brain damage in a comatose patient?
* **Flaccidity or no movement**
* Severe spinal/brainstem injury
* **Decerebrate posturing** (extension of arms/legs)
* Subcortical injury
* **Decorticate posturing** (flexion of arms & extension of legs)
* Bilateral cortical injury
* **Asymmetric responses**
* Hemispheric injury
58
What are some **abnormal respiratory responses** that can indicated injury in a comatose patient?
* **Hypoventilation**
* Opiate or sedative overdose
* **Hyperventilation**
* Metabolic acidosis (Kussmaul respirations)
* Neurogenic pulmonary edema
* Midbrain injury
* **Cheyne-Stokes breathing**
* Alternating apneas & hyperpneas
* Bilateral cortical injury
* **Apneustic breathing**
* Pausing at full inspiration
* Pontine damage
* **Ataxic or agonal breathing**
* Irregular respirations w/ no pattern
* Medullary injury
* Impending brain death
59
How do **pupillary size & reactivity** provide clues to brain injury in a comatose patient?
* **Unilateral dilated nonreactive pupil**
* Uncal herniation
* **Bilateral dilated nonreactive pupils**
* Topical application of a dilating agent
* Postictal state
* Irreversible brainstem injury
* **Bilateral constricted reactive pupils**
* Opiate ingestion
* Pontine injury
60
What is the **Oculocephalic maneuver** (doll's eyes)?
* When turning the head of an unconscious patient, the eyes normally look straight ahead & then slowly drift back to the midline position
* Intact vestibular apparatus senses a change in position
* **Injured brainstem**
* Movement of the head does not evoke any eye movement
* Negative oculocephalic maneuver
* "negative doll's eyes"
61
What is **Caloric Irrigation**?
* Performed when oculocephalic response negative or can't be performed
* Angle the head at 30o
* Irrigate each auditory canal w/ 10-30 mL of ice water
* **Intact (normal) cold caloric response**
* Eye deviation to the irrigated side
* **Abnormal response**
* Pontine injury
62
Abnormal _____ & _____ reflexes indicate significant brainstem injury.
corneal, gag
63
How is a comatose patient diagnostically worked up?
* Glucose check immediately
* Urine toxicology screen, serum electrolytes, metabolic panel
* Head CT scan
* Identify mass lesions or trauma
* Lumbar puncture
* Rule out meningoencephalitis if CT neg
* Urgent EEG
64
What is a **seizure**?
* Transient, **involuntary** alteration of consciousness, behavior, motor activity, sensation or autonomic function
* Excessive **discharge** from population of cerebral neurons
65
What is epilepsy?
What is status epilepticus?
* **Epilepsy**
* 2 or more spontaneous seizures
* No obvious precipitating cause
* **Status epilepticus**
* Seizure _\>_30 min
* Pt doesn't regain consciousness
66
\_\_\_\_% of children have a single afebrile seizure before 16 years of age.
Fewer than ____ of children who have a single seizure go on to develop epilepsy.
Epilepsy has an incidence of \_\_\_\_\_% during childhood.
4-6%
1/3
0.5-0.8%
67
What is the **etiology** of seizures?
* Imbalance btwn excitatory & inhibitory input within the brain
* Abnormalities in the membrane properties of individual neurons
* In some children, cause of seizures is known
* **60-70% of cases, cause is unknown**
68
What are the 7 causes of **acute seizures** during childhood?
What are some examples of each?
* **Head trauma**
* Cerebral contusion, subdural hematoma
* **Brain tumor**
* Astrocytoma, meningioma
* **Toxins**
* Amphetamines, cocaine
* **Infections**
* Meningitis, encephalitis, brain abscess, neurocysticercosis
* **Vascular**
* Cerebral infarction, intracranial hemorrhage
* **Metabolic disturbances**
* Hypocalcemia, hypoglycemia, hypomagnesemia, hypo/hypernatremia, pyridoxine deficiency
* **Systemic diseases**
* HTN, hypoxic-ischemic injury, inherited metabolic disorder, liver disease, renal failure, neurocutaneous disorders (tuberous sclerosis)
69
What are the **criteria** for the classification of seizures?
* Presence or absence of fever
* Extent of brain involvement
* Whether consciousness is impaired
* Nature of the movements
70
What is the **classification** of seizures?
* **Febrile**
* Simple
* Complex
* **Afebrile**
* Partial (one hemisphere)
* Simple: consciousness not impaired
* Complex: consciousness impaired
* Generalized (both hemispheres)
* Tonic-clonic
* Tonic
* Clonic
* Myoclonic
* Absence
* Atonic
71
What are **tonic-clonic** seizures?
* **Most common type of generalized seizure**
* Characterized by:
* Increased thoracic & abdominal muscle tone, followed by clonic movements of the arms & legs
* Eyes rolling upward
* Incontinence
* Decreased consciousness
* **Postictal state** of variable duration
72
What are **absence** seizures?
* Brief staring spells
* Occur w/o loss of posture
* Minor motor manifestations
* Eye blinking or mouthing movements
* \<15 seconds
* **No postictal state**
73
What are **partial (focal)** seizures?
What are the symptoms?
* Discharge of group of neurons in one hemisphere
* Motor, sensory, psychomotor features
* **Simple partial seizures**
* Consciousness not impaired
* **Complex partial seizures**
* Consciousness decreased
74
How is **epilepsy** classified?
* Predominant seizure type
* Site of origin of epileptic discharge
75
What is the **differential diagnosis** of seizure-like events?
* Breath-holding spells (infants)
* GERD (Sandifer syndrome)
* Syncope
* Migraine
* Vertigo
* Movement disorder (tics, chorea)
* Sleep disturbances (night terrors, somnambulism)
* Transient ischemic attack
* Rage attacks
* Psychogenic seizures
76
How are seizures diagnosed?
* **EEG**
* Identifies focus & pattern of epilepsy
* Abnormal EEG not required for diagnosis
* **Video-EEG monitoring**
* Useful when clinical info inadequate
* Pts \<3 YO, sleep seizures, poor historians
* **Neuroimaging studies**
* Should be performed in _all children_ except those w/ absence seizures or benign rolandic epilepsy
77
What are the steps in evaluating a seizure patient?
What are some important labs?
* ABCs
* Laboratory studies
* **Afebrile seizures**
* 1st time in healthy child w/ normal neuro exam is fine
* Serum electrolytes & neuroimaging in child w/ prior afebrile seizures
* **Febrile seizures**
* CNS infection MUST be ruled out
* Examination of CSF
* CBC, CXR, urine & blood cultures
78
How is **status epilepticus** treated?
* IV anti-convulsants
* **Short-acting benzodiazepine**
* Lorazepam, diazepam
* Loading dose of **phenobarbital** or **phenytoin**
79
How is epilepsy treated?
* Pharmacotherapy
* Single drug therapy
* **Generalized epilepsy**: valproic acid or phenobarbital
* **Absence epilepsy**: ethosuximide
* **Partial epilepsy**: carbamazepine or phenytoin
* Surgery
* **Medically intractable epilepsy**: surgery to remove epileptic tissue
* Best prognosis: temporal lobe lesions (75% complete control/remission)
80
What are some treatment alternatives for epilepsy? (besides drugs/surgery)
* **Vagal nerve stimulator**
* Pacemaker-sized device that sends electrical impulse to the vagus nerve
* Side effect: hoarseness
* **Ketogenic diet**
* High fat, low carb diet
* State of ketosis suppresses seizure activity
81
What is the **prognosis** of epilepsy?
* **Epilepsy is not a lifelong disorder**
* 70% of children can be weaned off their meds
* After 2 yr seizure free period & normalization of EEG
82
**Febrile Seizures**
* definition
* epidemiology
* etiology
* **Any seizure accompanied by a fever owing to a non-CNS cause in patients 6 mo to 6 YO**
* Common, 3% of all children
* Pathophysiologic mechanism unknown
* Can be inherited (several gene mutations found)
83
Simple vs. Complex Febrile Seizures
* **Simple febrile seizure**
* \<15 min, generalized
* **Complex febrile seizure**
* \>15 min, focal, recurs w/i 24 hrs
84
How are febrile seizures diagnosed?
* History, normal neurologic exam, exclusion of any CNS infection
* Lumbar puncture only if _meningitis suspected_
* Neither neuroimaging or EEG needed unless _neurologic exam abnormal_
85
How are febrile seizures managed?
* **First-time or occasional**
* Not treated
* Aggressive anti-pyretic treatment of subsequent febrile illnesses may help prevent febrile seizures
* **Frequent, recurrent**
* Daily anticonvulsant prophylaxis
* Valproic acid, phenobarbital
* Abortive treatment w/ rectal diazepam
86
Approximately \_\_\_\_% of pts w/ one febrile seizure will have a recurrence. Recurrence risk _____ with increasing patient age. The risk of epilepsy is \_\_\_\_%.
30%, decreases, 2% (low)
87
What are **epileptic syndromes**?
How are they classified?
* Epileptic conditions characterized by a specific age of onset, seizure characteristics, EEG abnormality
* 3 of the most common
* **Infantile spasms**
* **Absence epilepsy of childhood**
* **Benign rolandic epilepsy**
88
**Infantile spasms (West syndrome)**
age of onset
etiology
* Age of onset: **3-8 mo** (rare in children \>2 YO)
* **Tuberous sclerosis** is the most commonly identified cause of infantile spasms
* PKU, hypoxic-ischemic injury, intraventricular hemorrhage, meningitis, encephalitis
89
What are the clinical features of **infantile spasms**?
How is it diagnosed?
* Brief, myoclonic jerks, lasting 1-2 sec each
* Clusters of 5-10 seizures over 3-5 min
* **Sudden arm extension or head & trunk flexion**
* "jackknife seizures", "salaam seizures"
* EEG
* **Hypsarrhythmia pattern**
* Highly disorganized pattern of high amplitude spike & waves in both cerebral hemispheres
90
How are **infantile spasms** managed?
What is the prognosis?
* **ACTH IM injections**
* 4-6 wks, effective in \>70% pts
* **Valproic acid**
* Second-line drug of choice
* **Vigabatrin**
* Most effective for those w/ tuberous sclerosis
* Outlook is _poor_
* Moderate-severe mental retardation
91
**Absence epilepsy of childhood**
age of onset
etiology
* Age of onset: 5-9 YO
* Female:Male = 3:2
* Autosomal dominant inheritance
* Age-dependent penetrance
92
What are the **clinical** features of absence epilepsy of childhood?
* Absence seizures **5-10 sec**
* Frequent, tens to **hundreds** of times per day
* Accompanied by **automatisms**
* Eye blinking, incomprehensible utterances
* Loss of posture, urinary incontinence, postictal state do NOT occur
93
**Absence epilepsy of childhood**
* diagnosis
* management
* prognosis
* EEG
* Generalized **3 Hz spike & wave discharge**
* Both hemispheres
* Treatment
* **Ethosuximide** (1st line) or valproic acid
* Outlook is very good
* **Seizures resolve in adolesence**
* No cognitive impairment
94
**Benign rolandic epilepsy**
(benign centrotemporal epilepsy)
* definition
* epidemiology
* etiology
* **Involves nocturnal partial seizures w/ secondary generalization**
* Most common partial epilepsy during childhood
* 15% of epilepsy
* Presents at 3-13 YO
* Peak incidence: **6-7 YO**
* Boys \> girls
* **Autosomal dominant, variable penetrance**
95
What are the clinical features of benign rolandic epilepsy?
* Seizures in early morning hours
* **Oral-buccal manifestations**
* Moaning, grunting, pooling of saliva
* Seizures spread to face & arm
* **Generalize to tonic-clonic seizures**
96
**Benign rolandic epilepsy**
* diagnosis
* management
* prognosis
* EEG
* Biphasic spike & sharp wave disturbance in the mid-temporal & central regions
* Treatment
* **Valproic acid** (1st line), carbamazepine
* **Outcome is excellent**
* Seizures remit spontaneously during adolescence, no effects on development
97
What are the **intracranial** causes of a headache?
* **Primary headaches**
* Primary dysfunction of neurons
* Migraine headache
* Primary dysfunction of muscles
* Tension headache
* **Secondary headaches**
* Increased ICP
* Hydrocephalus, brain tumor, subdural hematoma
* Meningeal irritation
* Meningitis, subarachnoid hemorrhage
98
What are the **extracranial** causes of a headache?
* **Local causes**
* Ears: otitis media
* Eyes: refractive rror, glaucoma
* Nose: sinusitis
* Mouth: toothache, abscess
* TMJ dysfunction
* **Systemic causes**
* Anemia (children)
* Depression (adolescents)
* Hypoglycemia (children)
* HTN (adolescents)
* Psychogenic
* CO poisoning
99
What are the 4 pieces of **clinical information** that help determine the cause of a headache?
* **Quality of pain**
* Migraine: throbbing/pounding
* Tension: aching/pressure
* **Site & radiation**
* Migraine: unilateral, periorbital to forehead & occiput
* Tension: generalized/bitemporal
* **Time of onset**
* Tension: end of day
* Increased ICP: morning
* **Duration**
* Shorter duration, less likely serious
100
What is a **migraine**?
* Prolonged (\>1 hr), unilateral headaches
* Nausea, vomiting, visual changes
* Caused by changes in cerebral blood flow
101
**Migraines** are the most common cause of headaches in children & adolescents, occuring in up to \_\_\_% of school-age children.
Age of onset is younger than \_\_\_\_yrs in \_\_\_\_\_%.
Before puberty, (M/F) dominant.
After puberty, (M/F) dominant.
5%
5 years, 20%
M\>F
F\>M
102
What is the etiology of migraines?
* **Autosomal dominant**
* \>80% of children have at least 1 affected parent
* Changes in cerebral blood flow secondary to **release of serotonin** (5-HT), substance P & VIP from changes in neuronal activity
103
How are **migraines** classified?
* **Migraine w/o aura**
* Most common form in children
* No warning symptoms
* **Migraine w/ aura**
* Preceded by transient visual changes
* Blurred vision, small areas of decreased vision (scotomata), streaks of light, hemianopsia, unilateral pressure/weakness
* **Migraine equivalent**
* Young children, headache absent
* Prolonged, transient alteration of behavior
* Cyclic vomiting, cyclic abd pain, paroxysmal vertigo
104
Migraines are associated w/ what **focal neurologic signs**?
* **Ophthalmoplegic migraine**
* Unilateral ptosis or cranial nerve III palsy
* **Basilar artery migraine**
* Vertigo, tinnitus, ataxia, dysarthria
105
What are the precipitating factors in migraines?
* **No obvious precipitating cause**
* Many sufferers sensitive to vasoactive substances in certain wines, cheeses, preserved meats & chocolate
* Some patients have headaches induced by stress, fatigue, menstruation, exercise
106
What are the 7 main clinical features of migraines?
* **Prolonged, throbbing, unilateral headache**
* Supraorbital area & radiates to occiput
* Young children: bifrontal
* **Nausea & vomiting**
* Motion sickness common
* **Visual disturbances**
* Blurred vision, scotomata, jagged streaks of light that outline old forts (fortifications)
* **Photophobia or phonophobia**
* Treat by lying in dark, quiet room
* Over-the-counter analgesics _ineffective_
* **Symptoms improved by sleep**
* **Neurologic exam normal**
107
**Migraines**
* diagnosis
* management
* prognosis
* Hx & normal neuro exam
* Rest & elimination of known triggers
* Abortive treatment
* **Sumatriptan**: selective 5-HT agonist
* Injectable, intranasal, oral
* Prophylaxis
* **Propranolol**
* Lifelong disorder w/ waxing & waning course
108
What is a **tension** headache?
What age is most common?
* Bifrontal or diffuse, dull, aching headaches
* Associated w/ **muscle contraction**
* Unusual during childhood
* Extremely rare in children \<7 YO
109
What are the clinical features of a tension headache?
* **Dull, aching, rarely throbbing**
* Increases in intensity during the day
* Pain usually bifrontal, can be diffuse
* **Isometric contraction**
* Temporalis, masseter, trapezius
* No vomiting, visual changes, paresthesias
110
How are tension headaches diagnosed?
How are they managed?
* Tension headaches are **very rare in childhood**
* Other diagnoses (migraines) should be preferentially considered
* Treatment
* Reassurance & pain control
* Acetaminophen, ibuprofen
* Stress & anxiety reduction
111
What is a **cluster** headache?
What are the clinical features?
How is it treated?
* Extremely rare during childhood
* **Unilateral frontal or facial pain**
* Conjunctival erythema
* Lacrimation
* Nasal congestion
* \<30 minutes, several times a day
* **May not occur for wks-mo**
* Treatment
* Abortive therapy: oxygen, sumatriptan
* Prophylaxis: Ca2+ blockers, valproic acid
112
What is **ataxia**?
* **Inability to coordinate muscle activity during voluntary movement**
* Involves trunk or limbs
* Caused by cerebellar or proprioceptive dysfunction
113
What is the differential diagnosis of **unsteady gait**?
* **Cerebellar dysfunction**
* Unsteady wide-based stance
* Irregular steps & veering to one side/other
* **Weakness**
* Muscle weakness: spinal cord lesions, acute disorders of motor unit (Guillain-Barre)
* **Encephalopathy**
* Infection, drug overdose, recent head trauma (decreased consciousness)
* **Seizures**
* During a seizure or postictal period
* **Vision problems**
* **Vertigo**
* Migraines, acute labyrinthitis, brainstem tumors
114
What is the differential diagnosis of **cerebellar ataxia**?
* **Brain tumors**
* Cerebellar astrocytoma
* Cerebellar primitive neuroectodermal tumor (medulloblastoma)
* Neuroblastoma
* **Trauma**
* Cerebellar contusion
* Subdural hematoma
* **Toxins**
* Ethanol
* Anticonvulsants
* **Vascular**
* Cerebellar infarction/hemorrhage
* **Infections**
* Meningitis
* Encephalitis
* **Inflammatory**
* Acute cerebellar ataxia of childhood
* **Demyelination**
* Acute disseminated encephalomyelitis
* Multiple sclerosis
115
What is **Acute Cerebellar Ataxia of Childhood**?
What is the age of onset & etiology?
* Unsteady gait secondary to a presumed **autoimmune** or **postinfectious** cause
* _Most common cause of ataxia in children_
* Age of onset: **18 mo to 7 yrs**
* Rarely in children \>10 YO
* Etiology
* Varicella, influenza, EBV, mycoplasma
* Ataxia follows viral illness by 2-3 wks
* **Immune complex deposition in the cerebellum**
116
What are the clinical features of acute cerebellar ataxia of childhood?
* **Truncal ataxia**
* Deterioration of gait
* Young children refuse to walk (fear of fall)
* **Slurred speech & nystagmus**
* Hypotonia & tremors less common
* **Fever is absent**
117
How is acute cerebellar ataxia of childhood diagnosed?
* Hx & physical exam
* Exclusion of other causes of ataxia
* **Urgent neuroimaging study necessary in all pts**
* Rule out life-threatening causes
* Tumors/hemorrhage in posterior fossa
* Head CT scan is normal
118
How is acute cerebellar ataxia of childhood managed?
* Treatment is **supportive**
* Complete resolution of symptoms: 2-3 mo
* Physical therapy may be useful
119
**Guillain-Barre Syndrome**
(acute inflammatory demyelinating polyneuropathy)
* definition
* etiology
* Demyelinating polyneuritis
* Ascending weakness, areflexia, normal sensation
* ***Campylobacter jejuni***
* Prodromal gastroenteritis
* CMV, EBV, HSV, influenza, varicella, Coxsackie virus
120
What is the **pathophysiology** of Guillain-Barre Syndrome?
* Principal sites of demyelination
* **Ventral spinal roots**
* **Peripheral myelinated nerves**
* Cell-mediated immune response to infectious agent that cross-reacts to antigens on the Schwann cell membrane
121
What are the 4 main clinical features of Guillain-Barre Syndrome?
* **Ascending, symmetric paralysis**
* May progress to respiratory arrest
* **No sensory loss occurs**
* Low back or leg pain (50%)
* **Cranial nerve involvement**
* Facial weakness (40-50%)
* **Miller-Fischer syndrome (variant)**
* Ophthalmoplegia
* Ataxia
* Areflexia
122
How is Guillain-Barre Syndrome diagnosed?
* **Lumbar puncture**
* Albuminocytologic dissociation
* Increased CSF protein in the absence of an elevated cell count
* 1 wk after symptom onset
* **EMG**
* Decreased nerve conduction velocity or conduction block
* **Spinal MRI**
* Children \<3 YO
* Rule out compressive lesions of spinal cord
123
How is Guillain-Barre Syndrome managed?
What is the prognosis?
* **IVIG**
* 2-4 days
* Preferred treatment for children
* **Plasmapheresis**
* 4-5 days
* Removes patient's plasma along w/ presumed anti-myelin Ab
* **Complete recovery is the rule in children**
* Physical therapy may be necessary
124
What is **Sydenham chorea**?
| (St. Vitus' dance)
* **Self-limited autoimmune disorder**
* Associated w/ rheumatic fever
* Presents with:
* Chorea
* Uncontrolled, restless proximal limb movements
* Emotional lability
125
Sydenham chorea occurs in approximately \_\_\_% of patients w/ rheumatic fever.
Onset is common btwn ___ & ___ yrs of age.
25%, 5-13 YO
126
What is the pathophysiology of Sydenham chorea?
Ab **cross-react** w/ membrane antigens on both group A ß-hemolytic streptococcus & basal ganglia cells
127
What are the 8 clinical features of Sydenham chorea?
* **Immunologic response (2-7 mo)**
* **Children appear restless**
* Face, hands, arms
* Movements continuous, quick, random
* **Speech jerky or indistinct**
* **Chameleon tongue**
* Patients unable to sustain protrusion of the tongue
* **Choreic hand**
* Wrist flexed & hyperextended at the metacarpal joints
* **Milkmaid's grip**
* Pts unable to maintain grip on examiner's fingers
* **Emotional lability**
* **Gait & cognition not affected**
128
What is the differential diagnosis of Sydenham chorea?
* Other conditions may cause chorea
* Acquired & congenital conditions
* Encephalitis
* Kernicterus
* SLE
* Huntington's disease
* Wilson's disease
129
How is Sydenham chorea diagnosed?
* No single confirmatory test
* **Elevated ASO or anti-DNase B titer**
* Recent strep infection
* Neuroimaging
* **Head MRI**
* Increased signal intensity in the caudate & putamen on T2 weighted
* Single-photon emission computed tomography (**SPECT**)
* Increased perfusion to thalamus & striatum
130
How is Sydenham chorea managed?
What is the prognosis?
* **Haloperidol, valproic acid, phenobarbital**
* Symptoms: several months to 2 yrs
* Generally, all patients recover
131
What is **Tourette Syndrome**?
What is the prevalence?
What is the etiology?
* Chronic, lifelong movement disorder
* Motor & phonic tics _\<18 YO_
* **Tics are brief, stereotypical behaviors** that are initiated by an unconscious urge that can be temporarily suppressed
* 1 in 1,000 live births; 3% of children
* Cause is _unknown_
132
What are the clinical features of Tourette syndrome?
* **Motor tics**
* Simple: eye blinking, head/shoulder shaking
* Complex: bouncing, jumping, kicking
* **Phonic tic**
* Simple: cough, groan, bark
* Complex: echolalia (repetition of heard words/phrases)
* **Tics present _\>_1 yr**
* **Absence of signs of neurodegenerative disorder**
* **Coprolalia**
* Utterance of obsence words (15%)
* **Associated findings**
* Learning disabilities
* Attention deficit/hyperactivity disorder
* Obsessive compulsive traits
133
What is the differential diagnosis of Tourette syndrome?
* Disorders that may cause tics
* Wilson's disease
* Sydenham chorea
* Partial seizures
* Pediatric autoimmune neuropsych disorders associated w/ streptococcal infection (PAN-DAS)
* Simple habits
* **Habits are situation-dependent & under voluntary control**
134
How is Tourette syndrome diagnosed?
* Clinical diagnosis: hx & neuro findings
* No lab or imaging tests
135
How is Tourette syndrome managed?
What is the prognosis?
* **Pimozide (drug of choice)**
* Effective, minimal extrapyramidal SE
* **Clonidine**
* Less effective than pimozide
* Major SE: sedation
* **Haloperidol**
* Risk of tardive dyskinesia
* **Hyponotherapy**
* Effective in some patients
* _Tics decrease in adulthood_
* Pharmacotherapy successful, SE limiting
136
**Duchenne & Becker Muscular Dystrophies**
* definition
* epidemiology
* etiology
* **Progressive, X-linked myopathies**
* Myofiber degeneration
* DMD more severe than BMD
* **Deletion in dystrophin gene**
* All ethnic groups
* 1 in 25,000 live births
* Onset 2-5 YO
137
What is the **pathophysiology** of DMD & BMD?
* Dystrophin
* High molecular weight cytoskeletal protein
* Associates w/ actin & other structural membrane elements
* Absence of dystrophin
* **Weakness & rupture of plasma membrane**
* **Injury & degeneration of muscle fibers**
138
How do DMD & BMD appear on light microscopy?
* _Degeneration_ & _regeneration_ of muscle fibers
* Infiltration of **lymphocytes** into the injured area & replacement of damaged muscle fibers w/ **fibroblasts & lipid deposits**
139
What are the clinical features of **DMD** & **BMD**?
What are the similarities/differences?
* Slow, progressive weakness (legs first)
* Loss of ability to walk
* DMD: 10 YO
* BMD: _\>_20 YO
* **Psuedohypertrophy of calves**
* Excess accumulation of lipids
* Replace degenerating muscle fibers
* DMD \> BMD
* **Gower's sign**
* Weakness of pelvic muscles
* Pts extend each leg & "climb up" each thigh
* **Cardiac involvement (50%)**
* Cardiomegaly, tachycardia, cardiac failure
* **Cognition**
* DMD: mild cognitive impairment
* BMD: normal intelligence
140
How are DMD & BMD diagnosed?
* _Presence of enlarged calf muscles in a young boy w/ muscle weakness_ suggests diagnosis
* **CK level elevated**
* **EMG**
* Small, polyphasic muscle potentials
* Normal nerve conductions
* **Muscle biopsy**
* Typical dystrophic pattern
* **Absent/decreased dystrophin levels**
* IHC, Western blot
* **DNA testing**
* Gene deletion (90%)
141
How are DMD & BMD managed?
* **No cure**
* **Oral steroids improve strength transiently**
* Not successful in clinical trials
* Gene replacement
* Myoblast transplantation
* Dystrophin replacement
142
What is the prognosis of DMD? BMD?
* **DMD**
* Wheelchair dependent by 10 YO
* Die in late teens from respiratory failure
* Assisted ventilation may help
* **BMD**
* Wheelchair dependent in 20s
* Life expectancy in 50s
143
**Myasthenia Gravis**
* definition
* etiology
* boys vs. girls
* Autoimmune disorder
* Progressive weakness or diplopia
* **Ab against ACh receptor at NMJ**
* Girls 2-6X more than boys
144
What is the classification system of Myasthenia Gravis?
* **Neonatal myasthenia**
* Transient weakness in the newborn period
* Secondary to _transplacental transfer_ of maternal AChR ab from the mother with myasthenia gravis
* **Juvenile myasthenia**
* Presents in childhood
* Secondary to AChR ab formation
145
What are the **clinical** features of myasthenia gravis?
* _Neonatal myasthenia_
* Hypotonia, weakness, feeding problems
* _Juvenile myasthenia_
* **Bilateral ptosis** (most common)
* Characteristic increasing **weakness** later in the day w/ sustained muscle activity
* **Diplopia** secondary to decreased extraocular movements
* DTRs preserved
* Other autoimmune disorders (JRA, DM, thyroid disease)
146
How is myasthenia gravis diagnosed?
* **Tensilon test**
* IV injection of _edrophonium chloride_
* Rapidly acting cholinesterase inhibitor
* Transient improvement of ptosis
* **Decremental response** to low freq (3-10 Hz) repetitive nerve stimulation
* Presence of **AChR ab titers**
147
How is **myasthenia gravis** managed?
Neonatal vs. Juvenile?
* _Neonatal_
* Treatment **symptomatic**
* Compromised respiration: cholinesterase inhibitors or IVIG
* _Juvenile_
* Cholinesterase inhibitors
* **Pyridostigmine bromide**
* Immunotherapy
* **Corticosteroids**
* **Plasmapheresis lowers AChR ab**
* When symptoms worse, respiratory effort compromised, pt unresponsive
* **IVIG**
* Thymectomy
148
What is the prognosis of Myasthenia Gravis?
* **Neonatal**
* Symptoms mild & resolve 1-3 wks
* **Juvenile**
* Remission after thymectomy (60%)
