DOI: https://doi.org/10.21203/rs.3.rs-1537857/v1
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare autoimmune peripheral nervous system disease characterized by progressive or relapsing symmetric weakness and sensory dysfunction. It may rarely cause cranial nerve neuropathy. Although cranial nerve involvement is rarer in CIDP than Guillain-Barré syndrome (GBS), it may occur in rapid-onset and relapsed courses. We present an 8-year-old boy with hypoglossal nerve involvement, which has not been previously described in children. No accompanying disorder or antibodies were identified. This report is the first case in the literature for hypoglossal nerve involvement in children with CIDP. This report expands on the phenotypic features of CIDP in children and highlights that CIDP may represent with hypoglossal nerve involvement in children.
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare autoimmune peripheral nervous system disease characterized by progressive or relapsing symmetric weakness and sensory dysfunction, which evolves in at least 8 weeks in the all-age groups(1). Unlike adults, the clinical manifestation of CIDP in children can occur in less than 8 weeks(2). It is difficult to distinguish from Guillain-Barré syndrome (GBS), especially when the symptoms develop in less than 4 weeks (acute CIDP). In rapidly progressive cases, the probability of cranial nerve involvement and sensory deficit increase(3).
Contrary to GBS, cranial nerve involvement is rare in children with CIDP, particularly hypoglossal nerve involvement is unusual. To date, only five adult CIDP patients with hypoglossal involvement have been reported (4, 5). Herein, we report the first pediatric case of CIDP in the literature presenting with hypoglossal nerve involvement who responded well to pharmacological therapy.
An 8-year-old boy with a diagnosis of relapsing-remitting CIDP was admitted to our outpatient clinic for the first time at the age of 4 months due to diarrhea and lower extremity immobility after routine vaccination. He was born after uneventful pregnancy and delivery, with non-consanguineous marriage. At this age, on neurologic examination, he had symmetrical absent deep tendon reflexes and reduced muscle strength in the bilateral lower extremities. Cranial magnetic resonance imaging (MRI) was normal. Spinal MRI demonstrated T2 and fluid-attenuated inversion recovery (FLAIR) hyperintensity in the spinal nerve roots. Cerebrospinal fluid (CSF) evaluation revealed increased protein level (92 mg/dl, normal range: 15–45 mg/dl). With these clinical and laboratory findings, he was misdiagnosed with GBS due to rapidly progressive course. He was treated with intravenous immunoglobulin (IVIg, total: 2gr/kg, 5 days). At 9 months of age, significant improvement in his motor developmental milestones was observed. At 12 months of age, he gradually lost sitting, and was diagnosed with CIDP by nerve conduction study, which was compatible with demyelinating motor-weighted polyneuropathy. The similar clinical relapse occured seven times at the age of 1-year, 1-year and 6-month, 1-year and 10-month, 2-year and 6-month, 4-year and 7-month, 5-year and 10-month, and 8-year and 4-month.
Despite multiple pharmacological combinations such as monthly IVIg (total: 1–2 g/kg, 2–5 days), monthly intravenous (IV) methylprednisolone (MP) (20–30 mg/kg/day, 3–5 days), oral MP (1–2 mg/kg/day, 3–12 months), azathioprine (1–2 mg/kg/day), and rituximab (375 mg/m2 weekly for 4 weeks), clinical relapse and recovery periods were observed. However, slowly progressive distal muscle weakness and mild distal muscle atrophy occurred in bilateral lower extremities. Moreover, gabapentin was added to the treatment for neuropathic pain.
After an relapse-free period of 2 years, the patient was admitted to our outpatient clinic due to drooling, facial asymmetry, and increased distal lower extremity weakness. Neurological examination revealed mild unilateral facial weakness, tongue deviation on protrusion, and mild asymmetric hemiatrophy without tongue fasciculation (Fig. 1). Significant muscle atrophy and weakness, and loss of pinprick sensations were observed in the bilateral distal lower extremities. Deep tendon reflexes were decreased bilaterally in the upper extremities and absent in the lower extremities. Moreover, dysarthria and dysphagia were noticed.
In laboratory tests, blood samples were analyzed for autoimmune processes (including antinuclear antibody, anti-double stranded DNA, thyroid function tests and autoantibodies, anti-Ro/La, rheumatoid factor, anti-ganglioside antibodies, and anti-neurofascin 155/186) and infectious agents (including serology of cytomegalovirus and hepatic viruses), and all were found negative. CD-59 expression on flow cytometry was normal. CSF analysis was not repeated at the last relapse. According to the final nerve conduction study (Table 1), in the upper extremity, the distal latencies of the motor nerve were found prolonged, the amplitudes were found decreased, and the nerve conduction velocities were found at the lower limit. In the upper extremity, the distal latencies of the sensory nerve were found normal, the amplitudes were found decreased, and the nerve conduction velocities were found at the lower limit. Right median nerve F response was found prolonged. The lower extremity motor nerve conductions could not be obtained. In the lower extremity, the amplitudes of the sensory nerve were found decreased, the distal latencies were found prolonged, and the conduction velocities were found at the lower limit. These findings were compatible with motor-weighted demyelinating chronic polyneuropathy, accompanied by axonal involvement. Cranial MRI was also normal in the last attack. The patient was treated with monthly IVIg (total 2 g/kg, 4 days) and soon after weekly rituximab (375 mg/m2 weekly for 4 weeks). In the 3rd month of immunotherapy, hypoglossal nerve involvement improved significantly (Fig. 2).
| Nerve | Left | Right | ||||
|---|---|---|---|---|---|---|
| Motor Nerve | MCV (m/s) | CMAP (mV) | Distal latency (ms) | MCV (m/s) | CMAP (mV) | Distal latency (ms) |
| Median nerve | 46.7 | 0,00 | 4 | |||
| Ulnar nerve | 45 | 0,870 | 4 | |||
| Peroneal nerve | no response | no response | no response | no response | no response | no response |
| Sensory nerve | SCV (m/s) | SNAP (µV) | Distal latency (ms) | SCV (m/s) | SNAP (µV) | Distal latency (ms) |
| Median nerve | 41.3 | 27.5 | 2.3 | |||
| Ulnar nerve | 44.2 | 11.8 | 2.26 | |||
| Sural nerve | 41.7 | 4.5 | 3.6 | 47,6 | 9.1 | 2.94 |
| F wave conduction velocity | ||||||
| Median nerve | 35.75 | |||||
According to guideline of European Academy of Neurology/Peripheral Nerve Society, clinical and laboratory findings such as progressive distal weakness, involvement of more than two sensory and motor nerves in nerve conduction studies, increased protein in CSF examination, spinal MRI findings, good response to immunomodulatory treatment in our patient were consistent with CIDP diagnosis. Our patient was misdiagnosed with GBS because the previously mentioned symptoms lasted less than 4 weeks. However, the first presentation of childhood CIDP could be confused with GBS and this condition is called acute CIDP(1). In a comparative study comparing the clinical findings of rapid and slow-onset CIDP, Cabasson et al. found that relapsing course, sensory and cranial nerve involvement were significantly more common in the rapid-onset group, similar to our patient(3). Although cranial nerve involvement is less common in CIDP than GBS, it often involves the facial nerve, similar to GBS(4). Moreover, hypoglossal nerve involvement is rare in both diseases.
In the presence of autoimmune, genetic and infectious diseases accompanying CIDP, the course of the disease may include atypical features such as cranial nerve involvement. In a study involving adults with CIDP, cranial nerve involvement was found to be more common in patients with CIDP accompanied by Sjögren's syndrome(6). In addition, oculomotor and abducens nerve palsy were reported in a patient with concurrent CIDP and myasthenia gravis triggered by CMV infection(7). On the other hand, no underlying factor was found in the detailed etiological evaluation of our case.
Multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) is the most common subtype of CIDP with cranial nerve involvement, which includes 2nd, 5th, 7th, 12th cranial nerves in adult patients(1, 4). It usually causes asymmetric weakness and sensory deficit in the upper limbs, and the lower limbs is rarely involved at the onset of the disease. It is also quite rare in childhood. In a study involving juvenile case series with CIDP, only a 12-year-old male was diagnosed with MADSAM(8). However, the involvement pattern of motor and sensory loss and the age of onset of our patient were not compatible with MADSAM.
In the presence of cranial nerve involvement in CIDP, it is recommended to investigate the underlying nodal and paranodal antibodies, especially including contactin-associated protein-1 (CASPR-1) and neurofascin-155 (NF-155)(1). Our patient was found negative for NF-155. But, we did not examine serum CASPR-1 antibody. This is a limitation of our study.
In conclusion, we described a rare cranial nerve involvement of CIDP with no underlying factor. This report is the first pediatric case in the literature for hypoglossal nerve involvement in CIDP. This report expands on the phenotypic features of CIDP in children and highlights that CIDP may represent with hypoglossal nerve involvement in children.
Ethics approval and consent to participate: Ethical approval was waived by the local Ethics Committee of Ankara University in view of the retrospective nature of the study and all the procedures being performed were part of the routine care. The study was conducted in accordance with the declaration of Helsinki. Written informed consent was obtained from the participant of the study. The statements of written informed consent from legally authorized parents were obtained and are available upon request.
Availability of data and materials: Data openly available in a public repository that issues datasets with DOIs.
Competing interests: The authors declare that they have no conflict of interest.
Funding: The authors received no financial support for the research, authorship, and/or publication of this article.
Authors' contributions: NYS and MY designed and conceptualized the study, NYS, MY and ATK drafted the manuscript. ÖB and ST revised the manuscript. All authors contributed to the article and approved the submitted version.
Acknowledgements: Not applicable.