Perinatal/Neonatal Case Presentation the Use of Baclofen in Full-Term Neonates with Hypertonia

Perinatal/Neonatal Case Presentation The Use of Baclofen in Full-Term Neonates with Hypertonia

Lisa R. Moran, PharmD routinely to assess hypertonicity in all age groups.3–5 Tone is Tricia Cincotta, OTR/L assessed on a scale from 0 to 4. The scale begins at 0, representing Kalpathy Krishnamoorthy, MD no increase in tone and ranges to 4, which is a considerable Robert M. Insoft, MD increase in tone with difﬁculty in passive movements.

CASE REPORTS The use of baclofen in neonates has been minimally reported. We report on Patient #1 two term neonates who were treated successfully for hypertonia with A 4030-g male was born at term to a 24-year-old gravida 1 para 1 baclofen. woman with an unremarkable pregnancy. Her blood type was A Journal of Perinatology (2005) 25, 66–68. doi:10.1038/sj.jp.7211194 positive, antibody negative, rubella immune, Hepatitis B surface antigen negative, RPR nonreactive, Group B Streptococcus positive and PPD positive with negative chest radiograph results. She presented at an outside hospital in labor, with rupture of INTRODUCTION membranes 4 hours prior to delivery and received three doses of ampicillin for GBS prophylaxis. The newborn male was born by Neonatal hypertonia, resulting from severe hypoxic–ischemic vaginal delivery with APGARs of 2 and 3, at 1 and 5 minutes, brain injury or developmental brain disorders, may lead to severe respectively, with no documented 10- and 15-minute APGAR scores. functional disability. Severe hypertonia can be associated with He did require CPR and intubation in the delivery room for feeding difficulties, pain, discomfort and severe disabling joint profound bradycardia and apnea. contractures. Providing adequate care for these hypertonic neonates Initial NICU course was complicated by profound four-extremity is often a challenging situation both for the caretakers and hypertonia, seizures and respiratory failure during his first family. Medications are rarely employed to treat neonatal month of life, but was subsequently extubated to room air. He was hypertonia. noted to have an absent gag and suck reflex, abnormal facial Baclofen is a GABA agonist that is used to reduce muscle tone in movements and required frequent suctioning. He received children with cerebral palsy and in adults with various spastic phenobarbital for seizure prophylaxis and had an abnormal disorders. It is absorbed rapidly enterally and readily crosses the initial EEG. Occupational therapy was consulted for tone blood–brain barrier. Baclofen causes presynaptic inhibition, 1 management and a general developmental evaluation. resulting in inhibition of mono- and polysynpatic reflexes. Phenobarbital was successfully discontinued and follow-up EEG Symptomatic relief of severe chronic spasticity has been noted 2 on day of life, DOL 32 showed no electrographic seizures. with baclofen therapy. Repeat brain MRI was diffusely abnormal and consistent with The use of baclofen in neonates for severe muscle spasticity has late subacute severe hypoxic–ischemic injury in both basal not been well documented. We report two cases detailing the use of ganglia and perirolandic regions with evidence of significant baclofen in term neonates with severe muscle hypertonia. Parental white matter injury. consent was obtained prior to the initiation of baclofen in each Neurodevelopmental handling and positioning techniques were patient. Both neonates were evaluated by the same occupational introduced into the infant’s care to manage progressing therapist using the modified Ashworth scale (MAS). Although the hypertonia. Reassessment on DOL 32 noted severe flexor synergy efficacy of the MAS tool has been shown in adults, it is utilized with scissoring of lower extremities, cortical fisting, arching and right head preference. The infant’s MAS was 3 bordering on 4 in both upper and lower extremities. Baclofen 0.5 mg/kg/day PG

Department of Pharmacy (L.R.M.), Massachusetts General Hospital, Boston, MA, USA; Department divided q6 h was initiated on DOL 36. Follow-up assessment at DOL of Occupational Therapy (T.C), Massachusetts General Hospital, Boston, MA, USA; Department of 39 noted a signiﬁcant decrease in arching and uncomfortable Pediatrics and Neurology (K.K), Massachusetts General Hospital, Boston, MA, USA; and Division behaviors. The MAS on DOL 39 was 3 throughout the upper of Newborn Medicine (R.M.I), Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. extremities, and decreased to 1 throughout the lower extremity,

Address correspondence and reprint requests to Robert Insoft, MD, NICU, Massachusetts General trunk and neck. Care and positioning of the infant was markedly Hospital, 55 Fruit Street, Founders 442, Boston, MA 02114, USA. improved after the introduction of baclofen. The infant was able to

maintain flexion at his trunk and could tolerate gentle range of demonstrated a mildly abnormal cortex without focality. EMG on motion through all extremities. This improvement allowed better DOL 3 was within normal limits. EEG on DOL 3 was abnormal due engagement with his environment, parents and caretakers. to presence of relatively excessive for age sharp activity over the left Baclofen was increased by 0.5 mg/kg/day each week for a final hemisphere, centrotemporal and occipital regions. Phenobarbital dose of 1.5 mg/kg/day. MAS decreased to 2 in the lower extremities was initiated and a repeat EEG on DOL 13 was essentially normal and 3 in the upper extremities. Final assessment prior to transfer to exhibiting no excessive sharp transients or electrographic seizures. a rehabilitation hospital noted increased tolerance for both upper A genetics workup did not reveal any specific disorder as well. and lower range of motion bilaterally. At follow-up at age 4 Occupational therapy was consulted for hypertonia and a months, this neonate was fixing and following more consistently, general developmental evaluation. DOL 1 assessment noted but was still receiving mostly gavage tube feeds. The patient was significant hypertonia, left side greater than right, lower extremities still on baclofen and his MAS scores were 1 in the lower extremities greater than upper extremities. The MAS was assessed then as 2 and 2 in the upper extremities (Figure 1). He was seizure free at throughout all extremities. Subsequent evaluations noted a marked this time. increase in her hypertonia and concern for observed infant discomfort during routine care (i.e. diaper change, position change Patient #2 and nurturing interaction with parents). Neurodevelopmental A 2780-g nondysmorphic female was born at term to a 28- year-old handling and positioning techniques were introduced into her care gravida 3 para 3 woman who had a pregnancy notable for a 17- to manage worsening hypertonia. She exhibited no immediate or week ultrasound visualizing a clubfoot. Amniocentesis was declined sustained signs of relief from her hypertonia with these inhibitory and a level II ultrasound noted no additional abnormalities. Her techniques. Her progressive hypertonia made positioning and hand blood type was A positive, antibody negative, rubella immune, splinting very difficult. The level of tonicity in the left lower Hepatitis B surface antigen negative, RPR nonreactive and Group B extremity was not evaluated secondary to a casted clubfoot. streptococcus negative. She presented at a community hospital in Baclofen 0.35 mg/kg/day PG divided q6 h was initiated on DOL labor, with rupture of membranes approximately 3 hours prior to 24. At this time, the right upper and lower extremities had an delivery. The newborn was born by normal spontaneous vaginal MAS 4 and the left upper extremity had an MAS 3. The delivery with APGARs of 8 and then 3, at 1 and 5 minutes, dose was increased by 0.5 mg/kg/week to a final dose of respectively. She went on to develop significant secretions and mild 1 mg/kg/day. tachypnea and grunting in the delivery room requiring vigorous After introduction of baclofen, this neonate was able to tolerate suctioning, facial CPAP and supplemental oxygen. Chest additional therapeutic activities such as developmental prone radiograph showed low long volumes. Hypertonia of the upper positioning, right-hand splinting and, more importantly, extremities with hand clenching was also noted and the newborn nurturing/social activities with her family. MAS decreased to 2 in was transported to our NICU. all extremities over the next 2 weeks and the infant was then Her hospital course was complicated by severe four-extremity transferred to a rehabilitation hospital on DOL 47. Follow-up at age hypertonia, seizures and transient respiratory distress. She was 4 months revealed a MAS of 1 throughout all her extremities and stable on room air within 24 hours of life. Neurology was consulted trunk (Figure 2), with her being maintained exclusively on gavage to evaluate the hypertonia and seizures. Brain MRI on DOL 2 tube feeds. She was seizure free at this time.

UE 4 LE 2 4 RUE/RLE 2 ) Baclofen LUE y

Baclofen /da 3 1.5 g

3 1.5 /k g

2 1 2 1 MAS score MAS scor 1 0.5 1 0.5 Baclofen Dose (m Baclofen Dose (mg/kg/day) 0 0 0 0 32 39 46 121 1 27 31 37 120 Day of Life Day of Life Figure 1. Patient #1 upper and lower extremities. Relationship Figure 2. Patient #2 right upper and lower extremities and left upper between baclofen dose and MAS. extremity. Relationship between baclofen dose and MAS.

Journal of Perinatology 2005; 25:66–68 67 Moran et al. Use of Baclofen in Full-Term Neonates

DISCUSSION some reports about baclofen’s effect on increasing seizure 7,8 The use of baclofen in the neonatal period has not been well activity; however, neither of our patients had any increase in documented. Based on the limited experience using baclofen for seizure frequency on baclofen therapy. the prevention and treatment of neonatal seizures following We report the successful and apparently safe use of baclofen for intrauterine baclofen exposure, a starting dose of 0.5 mg/kg/day PG two neonates with marked hypertonia. The use of baclofen in the was selected.6 The enteral route was selected due to ease of newborn period has not been previously well documented. We hope administration. The intrathecal route has been associated with these reports will help stimulate further studies into determining cardiovascular collapse, CNS depression and respiratory failure, and optimal dosing and long-term outcomes. is rarely used in infants.2 The dose was titrated to clinical response or a decrease in MAS. Following the initiation of baclofen therapy, both infants References exhibited improved regulation of tone and a decrease in MAS. 1. Young RR, Delwaide PJ. Drug therapy: spasticity (second of two parts). Occupational therapy routinely evaluated each neonate and N Engl J Med 1981;304:96–9. reported to the care team any changes in tone and range of 2. Sweetman S, editor. Martindale: The Complete Drug Reference. London: motion. These changes were taken into consideration in Pharmaceutical Press Electronic version, MICROMEDEX, Greenwood Village, determining baclofen dosage. Patient #1’s MAS decreased from 4 to CO (Edition expires 3/2004). 2 and 4 to 1 in the upper and lower extremities, respectively, with a 3. Bohannon RW, Smith MB. Interrater reliability of a modified Ashworth scale final baclofen dose of 1.5 mg/kg/day. Patient #2’s MAS decreased of muscle spasticity. Phys Ther 1987;67:206–7. from 4 to 1 and 3 to 1 in the right lower and left upper extremities, 4. Fosang AL, Galea MP, McCoy AT. Measurement of muscle and joint respectively, with a final baclofen dose of 1 mg/kg/day. No adverse performance in the lower limb of children with cerebral palsy. Dev Med Child drug effects were reported in either patient. Both infants displayed Neurol 2003;45:664–70. improved range of motion, a perceived decrease in pain and 5. Sanger TD, Delgado MR, Gaebler-Spira D. Classification and definition of disorders causing hypertonia in childhood. Pediatrics 2003;111:89–97. improved tolerance for routine care. Tolerance for socialization 6. Terrance CF, Fromm GH, Roussau MS. Baclofen: its effects on seizure and nurturing time with family was also enhanced. The frequency. Arch Neurol 1983;40:28–9. implementation of baclofen allowed for extremity splinting 7. Hansel DE, Hansel CR, Shindle MK, et al. Oral baclofen in cerebral palsy: preventing further loss of range of motion. Neither patient possible seizure potentiation? Pediatr Neurol 2003;29:203–6. exhibited known side effects, which may include drowsiness, 8. Ratnayaka BDM, Dhaliwal H, Watkin S. Neonatal convulsions after feeding intolerance, vomiting and constipation.2 There have been withdrawal of baclofen. BMJ 2001;323:85.

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