The diagnosis of peripheral polyneuropathy in children and the differential diagnosis among its various forms often present a challenge, also because electrodiagnostic studies can be painful and sometimes yield inconclusive results. This systematic review examines the role of nerve ultrasound (n-US) in the diagnosis and follow-up of pediatric polyneuropathies. We searched PubMed and Embase from 1975 to April 1, 2025. Included studies assessed patients aged ≤ 18 years with clinically and neurophysiologically confirmed polyneuropathy, providing pediatric-specific qualitative or quantitative n-US findings. Eighteen studies met the inclusion criteria. Six focused on acquired inflammatory polyneuropathies (three on Guillain-Barré Syndrome [GBS], three on Chronic Inflammatory Demyelinating Polyneuropathy [CIDP]), eight on Charcot-Marie-Tooth disease (CMT), two on lysosomal storage disorders, one on Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS), and one on mixed etiologies. Most (n = 7) were case reports. Cross-sectional area and nerve enlargement (NE) distribution were the main parameters evaluated. Marked, diffuse NE was found in demyelinating CMT and lysosomal disorders; CIDP showed diffuse and multifocal NE; GBS presented mild and proximal NE. No NE was reported in axonal CMT or ARSACS. Few studies assessed echogenicity or fascicular structure; none evaluated vascularization. n-US shows promise in differentiating demyelinating conditions such as CMT, CIDP, GBS, and certain metabolic syndromes in children. However, further age-matched control studies are needed, given that nerve growth and myelination peak between 15 and 17 years. Future research should explore n-US as an early diagnostic, screening, and follow-up tool.

We report the first documented familial occurrence of Anti-Neurofascin-155 (Anti-NF155) autoimmune nodopathy in both a father and his son. Anti-NF155 nodopathy can resemble chronic inflammatory demyelinating polyneuropathy (CIDP) but differs in its poor response to standard CIDP treatments such as intravenous immunoglobulin (IVIG) and steroids, instead requiring B-cell-depleting therapies. A previously healthy 34-year-old male presented with a five-to-six week history of subacute sensory ataxia, symmetric proximal and distal weakness, and areflexia, preceded by right-sided Bell's palsy. Cerebrospinal fluid (CSF) analysis demonstrated albumin-cytologic dissociation with a markedly elevated protein level of 485 mg/dL, and nerve conduction studies confirmed a demyelinating polyneuropathy. Despite treatment with IVIG and corticosteroids, he showed minimal improvement, and subsequent detection of Anti-NF155 antibodies in serum established the diagnosis. He improved significantly with rituximab therapy and was able to walk unassisted at 1-year follow-up. Notably, his 13-year-old son presented with a similar clinical syndrome at the age of 8, characterized by progressive bilateral weakness, sensory ataxia, tremor, elevated CSF protein of 201 mg/dL, diffuse nerve root enhancement on MRI, and demyelinating polyneuropathy on electrophysiologic studies. He was initially treated as CIDP but failed to respond to IVIG and steroids, later testing positive for Anti-NF155 antibodies, and has since achieved sustained improvement on rituximab maintenance every six months. This report emphasizes the possibility of genetic predisposition in the pathogenesis of Anti-NF155 nodopathy and underscores the need for further investigation into familial and environmental factors contributing to disease susceptibility.

Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune neuromuscular disorder characterized by proximal muscle weakness, autonomic dysfunction and hyporeflexia. Numerous studies have reported the association of LEMS with anti-SOX1 antibodies and small cell carcinoma, but LEMS with double antibody positivity and cerebellar ataxia accompanied by small cell carcinoma is relatively rare. A 56-year-old female patient developed progressive limb weakness in November 2023, with symptoms gradually worsening over six months to include gait instability, impaired grip, chest tightness, dyspnea, dysphagia, and aspiration. Electrodiagnostic testing confirmed Lambert-Eaton myasthenic syndrome (LEMS) with positive VGCC antibodies. Paraneoplastic antibody testing showed positive anti-CV2/CRMP5 antibodies (24 AU) and borderline anti-SOX1 antibodies (9 AU), while other antibodies were negative. Initial imaging (contrast-enhanced chest CT and PET-CT) revealed no abnormalities, but follow-up one year later detected mediastinal small cell lung cancer. The patient underwent three plasma exchange sessions with corticosteroid therapy with limited response, then showed significant improvement after switching to subcutaneous Telitacicept (80 mg) combined with Fampyra Comprimidos and Mycophenolate Mofetil capsules, achieving independent ambulation and normal grip strength with only mild residual limb weakness. The patient has since been transferred to a local hospital for chemotherapy. We find that LEMS with concurrent anti-SOX1 and anti-CV2/CRMP5 positivity manifests as rapid progression, prominent proximal weakness, and potential cerebellar and autonomic involvement. Early and sustained oncological surveillance—particularly of mediastinal lymph nodes—and combined immunotherapeutic strategies can significantly improve neurological outcomes.

Stiff-person syndrome (SPS) is an autoimmune disease associated mainly with antibodies to glutamic acid decarboxylase (GAD) or to glycine, characterised by intermittent painful spasms, stiffness and rigidity of the proximal and truncal muscles. Neuro-ophthalmological and gastrointestinal symptoms also occur. The symptoms are caused by neuronal excitability due to impaired inhibitory (gamma amino butyric acid [GABA] and glycine) neurotransmission. SPS is part of a larger spectrum of GAD antibody-spectrum disorders, which overlaps with autoimmune epilepsy, cerebellar ataxia, myoclonus, progressive encephalomyelitis, rigidity and myoclonus (PERM) and limbic encephalitis. PERM is often caused by antibodies against the glycine receptor. Some SPS cases are paraneoplastic. Diagnostic delay is often associated with irreversible disability, and therefore, clinicians need a high degree of clinical suspicion to make an earlier diagnosis. This review updates the various clinical presentations that should raise suspicion of SPS and its related conditions and includes a diagnostic algorithm and various treatment strategies including immunotherapy and GABA-ergic drugs.

Generally, paraneoplastic neurological syndrome (PNS) associated with anti-delta/notch-like epidermal growth factor-related receptor (anti-Tr/DNER) antibodies primarily presents with cerebellar ataxia and is frequently complicated by Hodgkin's lymphoma (HL). Extracerebellar manifestations are relatively rare, and cases in the absence of an underlying malignancy are rare. Here, we report a 60-year-old patient presenting with scanning speech, proximal limb weakness, gait ataxia, and a palpable neck mass. The paraneoplastic syndrome antibody test showed that both serum and cerebrospinal fluid (CSF) anti- Tr/DNER antibodies were positive. A 5-day regimen of intravenous immunoglobulin and high-dose dexamethasone led to neurological improvement. The patient exhibited enhanced proximal muscle strength (from grade 4- to 4+) in the lower extremities and partial recovery in coordination. The pathology of the right upper cervical mass was consistent with Warthin tumor. Re-examination of serum and cerebrospinal fluid Tr/DNER antibodies remained positive. We describe a case of probable PNS characterized by anti-Tr/DNER antibody-associated cerebellar ataxia and a pathologically confirmed benign Warthin tumor. This case expands the known phenotype of anti-Tr/DNER disorders, underscoring the importance of antibody testing in rapidly progressive cerebellar ataxia even in the absence of a detectable malignancy.