Levodopa‐Carbidopa Intestinal Gel in a Pediatric Parkinsonism‐plus Syndrome

In Parkinson's disease, levodopa (l‐dopa)‐carbidopa intestinal gel (LCIG) is indicated for the control of motor fluctuations, dyskinesias,1 and non‐motor symptoms.2 Here, we report the first case of LCIG in pediatric use. Our patient presented with upper limb tremor at 6 months and subsequently with axial hypotonia, dysphagia, and generalized dystonia. He did not achieve psychomotor development milestones: he could not stand, walk, or manipulate objects, and he never acquired verbal production. At 14 months, brain magnetic resonance imaging was normal, and cerebrospinal fluid examination showed low levels of homovanillic acid, neopterin, and biopterin. Sanger sequencing revealed no alteration in the CGH1 (guanosine triphosphate cyclohydrolase 1), SR (serine/arginine‐rich splicing family), or TH (tyrosine hydroxylase) genes. At 21 months, l‐dopa/carbidopa 5 mg/kg daily and selegiline 2.5 mg daily were introduced and produced improvement of dystonia, restoration of axial tone, and upper‐limb finalized movements. Since the age of 42 months, the child developed vertical ophthalmoplegia and a long‐term l‐dopa treatment syndrome. In the off‐medication condition, he was hypotonic and unable to perform any voluntary movement, and he could not open his mouth to be fed. In the on‐medication condition (lasting 1–2 hours), he was able to vocalize and eat, his axial tone improved, and he could sit. Generalized choreodystonic movements were present throughout the on‐medication period. Tolcapone was then introduced but was withdrawn 8 months later because of worsening of dyskinesias; several dopamine agonists (pramipexole, bromocriptine, and rotigotine) were poorly tolerated, causing excitement. At night, he had difficulty falling asleep, sleep fragmentation, restlessness, and tremor. Constipation and gastroesophageal reflux were relevant. When he was 6 years old, scintigraphy with ¹²³I‐N‐fluoropropyl‐2b‐carbomethxy‐3b‐(4‐iodophenyl) nortropane (¹²³I‐FP‐CIT) documented a markedly reduced striatal uptake.

At 7 years of age, the patient was treated with selegiline 5 mg and melevodopa/carbidopa 3 times daily (total daily dose, 140/35 mg: 40/10 mg when awakening and 3 subsequent doses of 33.3/8.3 mg every 3 hours). At the time, we evaluated the LCIG treatment with a 3‐day trial through a nasojejunal tube. Withdrawn selegiline, we set a morning dose of 2 mL (40 mg) and a 12‐hour continuous infusion of 0.5 mL (10 mg) per hour, which was gradually increased to 0.7 mL (14 mg) per hour. The boy achieved an improvement in motor condition. Percutaneous endoscopic gastrostomy with jejunal extension (PEG/PEJ) tube (Freka, 15/9 French; Fresenius Kabi, Ltd., Bad Homburg vor der Hohe, Germany) was then placed. In the following weeks, the morning dose was reduced to 0.1 mL (2 mg) to limit dyskinesias and excitation. The continuous dose was increased to 0.8 mL (16 mg) from 8:00 to 11:00 am and to 0.9 mL (18 mg) from 11:00 am to 10:00 pm. We set extra doses of 0.2 mL (4 mg) in the morning and 0.3 mL (6 mg) in the afternoon.

After 1 year, the child was stable and was interacting with gestures and vocalizations; he could be fed at any time and was less irritable. Dyskinesias were mild. Insomnia, sialorrhea, constipation, and gastroesophageal reflux were no longer reported. No adverse events linked to the device were observed.

LCIG was effective on motor and non‐motor symptoms. In this patient, with a narrow therapeutic window, LCIG allowed the modulation of therapy with small dose variations that otherwise were not achievable. Regular follow‐up was performed to control clinical evolution and metabolic conditions.3

Author Roles

1. Research Project: A. Conception, B. Organization, C. Execution; 2. Statistical Analysis: A. Design, B. Execution, C. Review and Critique; 3. Manuscript Preparation: A. Writing the First Draft, B. Review and Critique.

M.G.V.: 1A, 1B, 1C, 3A

F.B.: 1B, 1C, 3A

P.M.: 1C, 3B

M.E.L.: 1C, 3B

V.L.: 1A, 3B

A.R.B.: 1A, 1B, 3B

Disclosures

Ethical Compliance Statement: We confirm that we have read the Journal's position in issues involved in ethical publication and affirm that this work is consistent with those guidelines.

Funding Sources and Conflicts of Interest: The authors report no sources of funding and no conflicts of interest.

Financial Disclosures for the previous 12 months: Anna Rita Bentivoglio reports speakers’ fees from Merz, Allergan, Chiesi Pharmaceuticals, Ipsen, Lundbeck, and Abbvie; in addition, she reports research grants from Chiesi Pharmaceuticals, Ipsen, and Merz. Maria Gabriella Vita reports speakers’ fees from Chiesi Pharmaceuticals. The remaining authors report no sources of funding and no conflicts of interest.