eEdE-200-6875 Pediatric spinal nerve root enhancement: Clinical and differential considerations Marinos Kontzialis1, Hans Michell2, Andrea Poretti2, Thierry A.G.M. Huisman2 1Division of Neuroradiology and 2Pediatric Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA ASNR 53rd Annual Meeting, Chicago, April 25-30, 2015 mkontzi1@jhmi.edu

Disclosure We have nothing to disclose No relevant financial relations interfering with our presentation

Purpose Case-based review of pediatric nerve root enhancement Clinical and differential considerations

Introduction Pediatric spinal nerve root enhancement: Indicates blood-nerve-barrier disruption Is a nonspecific finding

2-year-old with ascending weakness Case 1 2-year-old with ascending weakness A B C Diffuse nerve root enhancement in the cervical (A), thoracic (B) and lumbar spine (C)

Guillain-Barré syndrome (GBS) Autoantibody-mediated acute motor weakness: Pathogenesis = molecular mimicry and cross reactive immune reaction Prevalence: 1.2-2.3/100,000 Usually preceding upper respiratory or GI infection (Campylobacter jejuni) Maximum weakness within 4 weeks Progressive weakness > 8 weeks  chronic inflammatory demyelinating polyneuropathy (CIDP) CSF = albumin-cytological dissociation

Guillain-Barré syndrome: MRI Nerve root enhancement: > 90% Different patterns of enhancement Diffuse = 68% Ventral roots = 27% Dorsal roots = 5%

Guillain-Barré syndrome: MRI Cranial nerve (CN) involvement = 50% Bilateral CN V enhancement (arrows)

Differential diagnosis 1 Transverse myelitis: Quicker presentation compared to GBS (hours- few days vs. several days) Sensory-motor level (not present in GBS) MRI: spinal cord signal abnormalities + enhancement 10-year-old with transverse myelitis presenting with quadriplegia over 24-48 h

Differential diagnosis 2 Guillain-Barré syndrome West-Nile virus radiculitis Poliomyelitis-like syndrome with acute flaccid paralysis + sensory sparing MRI: most often normal, but ventral nerve roots enhancement is possible Can look identical to GBS

Case 2 8-year-old with congenital HIV infection A B C Bilateral CN III enhancement (A) and diffuse nerve root enhancement and mild thickening (B, C)

Chronic inflammatory demyelinating polyneuropathy (CIDP) Inflammation mediated demyelination Prevalence: 1-7.7/100,000 Clinically heterogeneous, grossly symmetric sensory and/or motor neuropathy Develops over > 8 weeks (GBS < 4 weeks) No preceding infection CSF = increased protein, normal cell count  supportive of nerve root inflammation

Chronic inflammatory demyelinating polyneuropathy CIDP may occur in the context of: Hepatitis C Inflammatory bowel disease Monoclonal gammopathy of undetermined significance (MGUS) HIV/AIDS Organ transplant Connective tissue disorders

Chronic inflammatory demyelinating polyneuropathy MRI: enhancement + hypertrophy of root + plexus possible  widespread inflammation Can mimic neurofibromatosis type 1 16-year-old with thickening and mild enhancement of lumbar plexus (arrowheads) and sacral nerve roots (arrows)

Case 3 9-month-old from El Salvador with a 2-week Hx of fever, lethargy, and emesis A B C D Diffuse meningeal enhancement in the posterior fossa (B), around the cord (B), and cauda equina nerve roots (D). Minimal clumping of the nerve roots (D).

Case 3 A B C Basilar meningitis CN V enhancement CN VI, VII, VIII enhancement + rim enhancing lesion in the right middle cerebellar peduncle

Tuberculosis Most common infectious cause of spinal arachnoiditis (= inflammation of the meninges) CSF: increased protein, decreased glucose, increased cells (mainly lymphocytes) Nerve root enhancement = 30%, predominantly smooth

Case 4 3-year-old with subacute onset of bilateral facial weakness and dysarthria A B C Diffuse nerve root enhancement in the cervical (A), thoracic (B) and lumbar spine (C)

CN VII + VIII enhancement Case 4 CN III enhancement CN V enhancement CN VII + VIII enhancement

Bannwarth syndrome Lyme meningo-radiculo-neuritis caused by spirochete Borrelia burgdorferi Most common tick-borne disease in the US Geography, recreational habits, season (peak in the summer) are clues! Confirmed by serum + CSF antibodies CSF = lymphocytic meningitis Erythema migrans in 89% of children = facilitates the diagnosis

Bannwarth syndrome MRI: MS-like periventricular white matter lesions Cranial nerve enhancement Nerve root enhancement In the appropriate geographic + seasonal setting  facial diplegia/palsy = highly suggestive of Lyme disease, especially when coupled with erythema migrans

Case 5 13-year-old with progressive polyneuropathy Thickening of the cauda equina nerve roots without evidence of enhancement (not shown)

Case 5 CN III thickening + enhancement CN V thickening + enhancement CN VII, VIII thickening + enhancement

Charcot-Marie-Tooth disease Hereditary motor + sensory neuropathies Symmetric + predominately distal motor + sensory disturbances, slowly progressive course MRI: typically associated with marked thickening of the nerves (hypertrophic neuropathies)

Differential diagnoses Metachromatic leukodystrophy (MLD) + Krabbe disease Can present with diffuse cranial nerve and cauda equina enhancement May be simultaneous or precede typical white matter abnormalities  Consider measuring arylsulfatase A + galactocerebrosidase in all children with unexplained cranial nerve and caudal nerve root enhancement MLD Krabbe disease

Case 6 3-year-old with developmental delay + failure to thrive Diffuse leptomeningeal + subarachnoid enhancement Diffuse thickening of the nerve roots

Leptomeningeal enhancement coating bilateral CN V Case 6 Avidly enhancing pineal mass with diffuse leptomeningeal enhancement in the posterior fossa + around the cord Leptomeningeal enhancement coating bilateral CN V

Pineoblastoma with leptomeningeal carcinomatosis Neoplastic causes of nerve root enhancement in the pediatric population: Medulloblastoma Germinoma Pineoblastoma PNET Ependymoma Astrocytoma Lymphoma Leukemia

Smooth nerve root enhancement Most common, but least specific GBS West Nile virus radiculitis CIDP Lyme disease Tuberculosis

Nerve root enhancement + thickening CIDP CMT disease Leptomeningeal carcinomatosis (enhancement can be nodular)

Summarizing table Diagnosis Clinical CSF Clues Associations MRI GBS <4 weeks  protein Ascending paralysis, preceding infection 50% CN involvement nerve root enhancement CIDP >8weeks Progressive neuropathy Underlying disorder? Nerve root enhancement + thickening Meningitis Encephalopathy, meningeal signs Protein cells Fever Empiric treatment + CSF ± leptomeningeal and nerve root enhancement TB Cells  Gluc Think about risk factors of exposure Pulmonary TB Meningitis/arachnoiditis, tuberculomas, nerve root enhancement Lyme Rash CN VII palsy Season, recreational activities, geography Tick bite MS-like lesions, CN and nerve root enhancement CMT Hypertrophic neuropathies - Established diagnostic criteria Gene testing + nerve biopsy Nerve root and plexus thickening MLD Krabbe arylsulfatase A β-galacerebrosidase CN + nerve root enhancement early on Neoplastic Depends on primary Nodular enhancement Image entire neural axis

Take-home messages Pediatric nerve root enhancement = nonspecific Clinical presentation, imaging findings and CSF testing will point towards the right direction + guide further management mkontzi1@jhmi.edu

Suggested literature Zuccoli G et al. Redefining the Guillain-Barre spectrum in children: neuroimaging findings of cranial nerve involvement. AJNR 2011;32(4):639-42. Van Doorn PA et al. Clinical features, pathogenesis, and treatment of Guillain-Barre syndrome. Lancet Neurol 2008;7:939-50. Mulkey SB et al. Nerve root enhancement on spinal MRI in pediatric Guillain-Barre syndrome. Pediatr Neurol 2010;43(4):263-9. Vallat JM et al. Chronic inflammatory demyelinating polyradiculoneuropathy: diagnostic and therapeutic challenges for a treatable condition. Lancet Neurol 2010;9:402-12. Sharma A et al. MR imaging of tubercular spinal arachnoiditis. AJR 1997;168(3):807-12. Hildenbrand P et al. Lyme neuroborreliosis: manifestations of a rapidly emerging zoonosis. AJNR 2009;30:1079-87. Cellerini M et al. Imaging of the cauda equina in hereditary motor sensory neuropathies: correlation with sural nerve biopsy. AJNR 2000;21:1793-8. Morana G et al. Enhancing cranial nerves and cauda equina: an emerging magnetic resonance pattern in metachromatic leukodystrophy and Krabbe disease. Neuropediatrics 2009;40:291-4. Zapadka M. Diffuse cauda equina nerve root enhancement. J Am Osteopath Coll Radiol 2012; Vol. 1, Issue 1.