Pediatric Neurology Quick Talks Hypotonia Michael Babcock Summer 2013

Scenario 2 do M in the NICU Poor feeding and “weakness” Not intubated Delivered 37 weeks by C/S – failure to progress Poor maternal pre-natal care HC ~50% Exam – axillary slippage, reduced spontaneous movements, +head lag, normal suck. +awake

Hypotonia – Localize –> Central or Peripheral Central (brain/spinal cord) –Normal/mild weakness –normal bulk –normal/increased reflexes –Dysmorphisms –encephalopathy Peripheral (Anterior horn, peripheral nerve, NMJ, muscle) –Marked weakness –decreased bulk –decreased reflexes –no dysmorphisms –Awake, alert

Central Causes Sepsis Maternal narcotics Hypothyroid Prematurity HIE Down's Syndrome Prader-Willi Inborn Errors of Metabolism –Zellweger Cerebral dysgenesis

Peripheral Causes Anterior Horn –SMA –Pompe Peripheral Nerve (uncommon) –Inflammatory – GBS –Demyelinating –Axonal –Metabolic- Leigh Neuromuscular Junction –Myasthenias –Infantile botulism –Hypermagnesemia Muscle –Myopathy –Muscular dystrophy –Myotonic dystrophy –Metabolic myopathy

Perkowski's top 5 not to miss causes of floppy baby Down's syndrome Prader Willi Pompe (have heart problems) Zellweger Spinal Muscular Atrophy However, most common is HIE

History Mother – systemic illness, fever, substance abuse Pregnancy – polyhydramnios, fetal movement, abnormal lie Delivery – complicated/prolonged, trauma, Apgars Family history – delayed milestones, weakness, myotonia

Exam – Assess Tone Tone is resistance to stretch forces, develops with nervous system development, low tone is normal for premature infants – Ballard testing. Resting posture – assess resting posture when infant is quiet/drowsy –Hypotonic infant – frog leg position –Long-standing immobility can cause joint contractures – arthrogryposis Passive manipulation –Infants develop increasing flexor tone in extremities – causes increased recoil after limb is extended –Head control in vertical/horizontal suspension –Vertical suspension

Ballard Testing – Testing tone

Work Up Central –Electrolytes (Mg, Ca, Gluc) –TFT's –Brain imaging – U/S vs MRI –EEG –Karyotype, CMA –Metabolic work-up Peripheral –CK –EMG/NCS –muscle/nerve bx

Spinal Muscular Atrophy (SMA) AR – SMN1 gene – SMN protein (survival motor neuron); SMN2 gene regulates severity Weakness and atrophy of muscles, including tongue Symmetric weakness, more proximal than distal, more severe in LE Tongue fasciculations Absent DTRs Normal intellectual capacity Facial muscles typically spared early on Types –Type 1 – infantile - Werdnig Hoffman - <6mo. - never sit –Type 2 – intermediate - Dubowitz – 6-18 months – never walk –Type 3 – juvenile - Kugelberg-Welander – 18mo- 17 years. - able to walk initially, often lose this. –Type 4 – adult-onset

Myasthenias Congenital –Genetic disorder of NMJ –Hypotonia, weakness (ocular, bulbar, respiratory) Variable onset, sometimes in utero – arthrogryposis –Recurrent ALTEs –Fatigability, weak cry, feeding difficulties, episodic apnea –Sometimes respond to AchE inhibitors Transient neonatal –Transplacental transfer of AchR Antibodies. –10-15% of infant of myasthenic mothers –Hypotonia, weakness—bulbar and respiratory, within 4 days of birth –Good response to AchE inhibitors

Infant Botulism Weakness and hypotonia Can have hx of honey ingestion; though contamination from soil is most common Constipation is often first sign Eye findings, ophthalmoplegia – botulism is descending paralysis Can test stool Can give Human boutlinum immunoglobulin – 50mg/kg in first few days shortens course Often severe respiratory weakness requiring ventilation, prolonged course.

Prep Question During the health supervision visit for a 6 week old boy, his father expresses concern that his son “doesn’t look like” his other children. Growth parameters are normal except for a head circumference of 35.5 cm (<5th percentile). On PE, you note that the infant does not appear to fixate or track your face visually. There is a “slip through” on vertical suspension and “draping over” on horizontal suspension. DTRs are brisk. Moro reflex is present and brisk. Of the following, the MOST likely cause of this infants hypotonia is: Anterior horn cell disease Congenital brain malformation Congenital myasthenic syndrome Congenital myopathy Spinal cord disease

B. Congenital brain malformation Hypotonia –Localize! UMN vs. LMN signs, axial vs appendicular –Take into account growth parameters, especially HC, as well as features such as tracking Regarding other choices: –A. anterior horn cell disease – wouldn't cause microcephaly or increased reflexes –C. Congenital myasthenic syndrome – wouldn't cause microcephaly or brisk reflexes –D. Congenital myopathy – no microcephaly or poor visual tracking –E. Spinal cord disease – wouldn't cause microcephaly or poor visual tracking.

References Paediatr Child Health September; 10(7): 397–400.; PMCID: PMC ; A schematic approach to hypotonia in infancy Respiratory update.com