Neurological disorders, seizures and epilepsy

direct injection of local anesthetic agents into the fetal scalp (associated with transient bradycardia and fixed dilated pupils), severe anoxia, or congenital brain malformation

seizures noted in the delivery room are often caused by

infection or drug withdrawal

seizure in the first 5 days of life is most likely a result of

benign familial neonatal seizures

these seizures have onset on days 3-7 and resolve by 1-4 months, and are due to mutations in KCNQ2 and KCNQ3 potassium channel genes.

subarachnonid hemorrhage

In an infant who appears well, a sudden onset on days 1-3 of life of seizures that are of short duration and that do not recur may be the result of

local cerebral infarction

focal seizures are often the result of

define a simple febrile seizure

more than 15 min

focal or

more than 2 episodes in 24 hours

define a complex febrile seiizure

myoclonic seizures

-very brief LOC leading to the person's arms/legs jerkingg sharply and uncontrollably

tonic seizures

-instant LOC; person goes stiff and falls to the ground

tonic-clonic seizure

-instant LOC

-person will go stiff and then move into jerky movements

-may experience incontinence

absence seizures

-brief loss of awareness accompanied by eyelid flutter or simple automatisms

-usually 4-6 years old

-characteristic electroencephalographic (EEG) patterns consist of generalized 3-Hz spike-and-wave activity

hyperventilation

an absence seizure can often be provoked by

focal simple seizure

No LOC, experince altered feelings or sensation, symptoms depend on the area of the brain affected, usually 20-60 seconds, returns to the pre-seizure state and remembers of the event

focal complex seizure

previously termed complex partial seizures ) can have similar sensorimotor signs but also have associated alteration of consciousness. Although the child may not be completely unresponsive, subtle slowing or alteration of mental status (dyscognitive features) may occur

west syndrome (infantile spasm)

Brief contractions of the neck, trunk, and arm muscles, followed by a phase of sustained muscle contraction lasting less than 2 seconds. Spasms occur most frequently when the child is awakening or going to sleep. Each jerk is followed by a brief period of relaxation with repeated spasms in clusters of variable duration.

-infantile spasms, developmental regression, and dramatically abnormal EEG pattern (hypsarrhythmia)

triad of west syndrome

Hypsarrhythmia

a pattern of chaotic high-voltage slow waves, spikes, and polyspikes

-seen in west syndrome

3-8 months

peak age of onset of infantilie spasms

adrenocorticotropic hormone, high-dose oral corticosteroids, and vigabatrin

first line treatment for infantile spasms

Benign epilepsy with centrotemporal spikes (benign rolandic epilepsy)

Autosomal dominant genetic disorder linked to abnormal neuronal potassium channels. Otherwise well newborns present with focal seizures toward the end of the first week of life, leading to the colloquial term fifth-day fits . Response to treatment is generally excellent, and the long-term outcome is typically favorable

lennox-gastaut syndrome

Severe epilepsy syndrome with variable age of onset although most children present before age 5 years. Frequent, multiple seizure types including atonic, focal, atypical absence, and generalized tonic, clonic, or tonic-clonic semiologies characterize the disorder. Many children have underlying brain injury, malformations, or genetic etiologies. The seizures are typically difficult to control, and most patients have significant intellectual disability.

Absence seizures typically begin in the early school years and usually resolve by late childhood or adolescence. If absence does not remit, nearly half will go on to develop juvenile myoclonic epilepsy

prognosis of childhood absence epilepsy

Ethosuxamide

1st choice med for absence epilepsy

juvenile myoclonic epilepsy

Most common generalized epilepsy among adolescents and young adults.

-usually lifelong

juvenile myoclonic epiplepssy

Onset is typically in early adolescence with myoclonic jerks (exacerbated in the morning, often causing the patient to drop objects), generalized tonic-clonic seizures, and absence seizures. Seizures usually resolve promptly with anti seizure medication

-valproic acid

-levetiracetam lower risk (preferred in girls bc of less teratogenicity)

classic treatment of juvenile myoclonic epilepsy

(1) ongoing seizure activity for 5 or more minutes or (2) repetitive seizures without recovery of consciousness

define a neurologic emergency

Initial management is with a benzodiazepine and should be administered if the seizure persists longer than 5 minutes. Lorazepam, diazepam, and midazolam are all effective agents and should be given as an adequate single dose (rather than successive smaller doses), which can be repeated one time. IV administration is preferred. When IV access is not available, benzodiazepines may be administered via rectal, intranasal, buccal, or intramuscular routes.

initial management of status epilepticus

Lorazepam, diazepam, and midazolam

preferred benzos in acute seizure tx

-newborns and infants: phenobarbital

-older children: IV fosphenytoin, valproic acid, or levetiracetam

tx of ongoing seizures after two doses of benzodiazepine

cerebral palsy

A group of non-progressive, but often changing, motor impairment syndromes secondary to anomalies or lesions of the brain arising before or after birth

diagnosed in the first 18 months of life when they fail to attain motor milestones or show abnormalities such as asymmetric gross motor function, hypertonia, or hypotonia

when are most pts with CP diagnosed?

spastic cerebral palsy

-most common form of CP

-results from injury to the UMN of the pyramidal tract

-characterized by abnormal movement pattern, increased tone, or pathologic reflexes

dyskinetic cerebral palsy

CP type dominated by abnormal patterns of movement and involuntary, uncontrolled recurring movements

ataxic cerebral palsy

-results from cerebellar injury and features abnormal posturue or movement and loss of orderly muscle coordination or both

-type of CP

acute disseminating encephalomyelitis

Acute, inflammatory demyelinating disorder that may affect infants and children after a febrile illness. Children may present with a variety of symptoms and signs including monocular vision loss (e.g., acute optic neuritis), hemiparesis, ataxia, seizures, headache, weakness, or dysphagia.

Intestinal infection by Clostridium botulinum , which produces a neurotoxin that blocks presynaptic cholinergic transmission. Young age and the absence of competitive bowel flora predispose infants to this disease. Infants may ingest dust, soil, or food (e.g., honey, poorly canned foods) contaminated with spores

describe the pathophys of botulism in children

Infants typically present with constipation and poor feeding. Hypotonia and weakness develop progressively, along with cranial nerve dysfunction manifested by decreased gag reflex, diminished eye movements, decreased pupillary contraction, and ptosis.

presentation of botulinism in infants

duchenne muscular dystrophy

X-linked disorder (Xp21) that arises from a mutation in the dystrophin gene

Duchenne muscular dystrophy

-at about 2-3 years old, male develops an awkward gait and inability to run

-x of mild delay in motor milestones

-pseudohypertrophy of calves

by 12, most boys are not walking and use a wheel chair full time

prognosis of DMD

Studies have shown that chronic oral steroid therapy delays the motor disability and improves longevity by preventing cardiac and pulmonary decline, even after a boy stops ambulating.

potential pharm management of DMD

acute inflammatory demyelinating polyradiculoneuropathy

most common variant of guillan=barre syndrome

acute inflammatory demyelinating polyradiculoneuropathy

-GBS variant

classically occurs about 10 days after a respiratory or gastrointestinal infection (e.g., Mycoplasma pneumoniae or Campylobacter jejuni ). It is the most common cause of acute flaccid paralysis in children.

Guillain-Barre Syndrome (GBS)

Areflexia, flaccidity, and symmetric ascending weakness. Progression can occur rapidly, in hours, or more indolently over weeks. Typically, symptoms start with numbness or paresthesia in the hands and feet, then a heavy, weak feeling in the legs. Weakness ascends to involve the arms, trunk, and bulbar muscles (tongue, pharynx, larynx). Deep tendon reflexes are absent even when strength is relatively preserved.

sometimes normal early in the illness but classically shows elevated protein levels without significant pleocytosis (albuminocytologic dissociation)

LP findings of GBS

Most patients are treated initially with intravenous immunoglobulin (IVIG). Plasma exchange is an alternative option. Physical, occupational, and speech therapies are mainstays of treatment.

treatment of GBS

fluctuating skeletal muscle weakness

cardinaal feature of juvenile myasthenia gravis

transient myasthenic syndrome develops in the first hours to days after birth in neonates born to mothers with myasthenia gravis related to maternal anti-AChR antibodies

Signs include weak facial movements, poor feeding, hypotonia, respiratory difficulty, and variable extremity weakness

-presentation of babies born to myasthenia gravis mothers

require cholinesterase inhibitors and supportive care for a few days to weeks until the weakness remits.

treatment of transient myastheniaa gravis in neonates

some types can respond to pyridostigmine or other drugs that improve neuromuscular junction function, other types can be exacerbated by pyridostigmine

treatment of congenital myasthenic syndromes

spinal muscular atrophy

defined by progressive degeneration of anterior horn cells

severe hypotonia, generalized weakness, and facial involvement. Infants have normal cognitive, social, and language skills and sensation. Fasciculations are best identified by inspecting the tongue when the child is asleep. Deep tendon reflexes are absent. With disease progression, breathing patterns change. Weak intercostal muscles and a relatively stronger diaphragm result in a collapsed chest wall (bell-shaped chest) and prominent abdominal movements with rapid, shallow breathing.

features of spinal muscular atrophy type one

-deficient enzyme: galactocerebrosidase

-accumulated substrate: galactocerebroside

deficient enzyme and accumulated substrate of Krabbe disease

Krabbe disease

Caused by inability to produce one lysosomal enzyme

Person cannot produce myelin for nerve cells, which leads to severe damage to the nervous system

Krabbe disease

autosomal recessive lysosomal storage disease

-Peripheral neuropathy, destruction of oligodendrocytes, developmental delay, optic atrophy, globoid cells

Hunter syndrome

Mild hurler + aggressive behavior, no corneal clouding

Deficient enzyme → iduronate-2-sulfatase

Accumulated substrate → heparan sulfate, dermatan sulfate

deficient enzyme and accumuluated substrate in Hunter syndrome

Hunter syndrome

X-linked recessive

similar to Hurler, deficient L iduronosulfate sulfatase, accumulations of heparin sulfate and dermatan sulfate, hepatospenomegaly, micrognathia, retinal degeneration, joint stiffness, mental retardation, cardiac lesions p59

Hurler syndrome

autosomal recessive - corneal clouding, course facial features, joint stiffness, mental retardation, hepatosplenomegaly

Deficient enzyme → alpha-L-iduronidase

Accumulated substrate → heparan sulfate, dermatan sulfate

deficient enzyme and accumulated substrate in hurler syndrome

Rett syndrome

-Neurodevelopmental disorder that classically affects girls

-Development appears normal during the first 6-18 months of life, but this is followed by developmental regression, loss of purposeful hand movements, loss of verbal communication skills, gait apraxia, and stereotypic repetitive hand movements that resemble washing, wringing, or clapping of the hands. Girls also develop acquired microcephaly.

The etiology is a mutation on an X chromosome gene coding for methyl-CpG-binding protein 2 (MECP2) transcription factor

etiology of Rett syndrome

Tay-Sachs disease

-autosomal recessive

Progressive neurodegeneration, developmental delay, hyperreflexia, hyperacusis, "cherry red" spot on macula (lipid accumulation in ganglion cell layer), lysosomes with onion skin, no hepatosplenomegaly (vs niemann-pick

Deficient enzyme → hexosaminidase A

Accumulated substrate → GM2 ganglioside

deficient enzyme and accumulated substrate in Tay-sachs

-autosomal dominant

-mutations of NF1 gene which codes for tumor suppressor gene, neurofibromin

genetics associated with neurofibromatosis type 1

-cafe au lait spots

-cutaneous neuroffibromas

-iris hamartomas

cardinal features of neurofibromatosis type 1

neurofibromatosis type 1

The presence of six or more café-au-lait spots larger than 5 mm in a prepubescent child suggests the diagnosis.

-learning disability, scoliosis, seizures, moyamoya

-optic nerve gliomas, astrocytomas, malignant peripheral nerve tumors

common complications associated wit NF type 1

bilateral acoustic schwannomas, schwannomas of other cranial and spinal nerves, meningiomas, and glioma

NF type 2 preddispoess the pt to these kindd of tumors

Lisch nodules, café-au-lait spots, and axillary freckling (seen in NF1) are not features of NF2.

main difference between NF type 1 and NF type 2

Sporadic (not inherited) and is caused by a somatic mosaic mutation of the GNAQ gene

genetics associate with Sturge-Weber syndrome

-angiomas of the leptomeninges in association with ipsilateral port-wine stain involving the opthalmic division of the trigeminal nerve

main features of Sturge-Weber ssyndrome

Sturge-Weber syndrome

Skin and meningeal angiomatous lesions. Port-wine nevus: skin angioma in ophthalmic division of trigeminal nerve. Pial angiomas may result in chronic ischemia, gliosis, and gyral cortical calcifications. Enlargement of deep and subependymal veins may mimic arteriovenous malformations.

Tuberous sclerosis

Autosomal dominant disorder, is characterized by hamartomas in many organs, especially the brain, eyes, skin, kidneys, and heart.

May have retinal lesions (retinal hamartomas, white depigmented patches) and brain lesions (cortical tubers, subependymal nodules, hydrocephalus). Tubers in the cerebral cortex are areas of dysplasia that, in combination with other microscopic areas of abnormal development, are responsible for the symptoms of intellectual disability and epilepsy.

main features of tuberous sclerosis

tuberous sclerosis

Skin lesions: Adenoma sebaceum. Ash-leaf spots. Brain lesions: Subependymal hamartomas. Cortical tubers. Subependymal giant cell astrocytomas located at foramina of Monro (May lead to hydrocephalus)

Subependymal giant cell astrocytoma

Seen in 10% of patients with tuberous sclerosis (look for subependymal and cortical hamartomas). WHO grade I. Commonly calcifies. and slow-growing, with calcification a common feature. Almost always produces some degree of hydrocephalus.

Tuberous sclerosis

one of the most common causes of infantile spasms; in this context, the infantile spasms often respond to treatment with vigabatrin

facial angiofibromas

Multiple smooth-surfaced papules most often found on the nose or nasolabial fold in tuberous sclerosis

shagreen patches

Areas of rough, leathery, orange peel-like skin typically seen on the lower back or nape of the neck in tuberous sclerosis

-ash leaf spots

-facial angiofibromas

-shagreen patches

main extracerebral manifestations of tuberous sclerosis