Multiple endocrine neoplasia, type 2b: Phenotype recognition; neurological features and their pathological basis

Dyck, Peter James; Carney, J. Aidan; Sizemore, Glen W.; Okazaki, Haruo; Brimijoin, W. Stephen; Lambert, Edward H.

doi:10.1002/ana.410060404

Cited by 44 publications

(5 citation statements)

References 14 publications

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“…The cauda equina was partially ossified. In addition, thickening of the meninges of the spinal cord associated with neuromatous sprouting of small nerve fascicles in the leptomeninges, resembling findings reported for multiple endocrine neoplasia, type 2b MEN2b [ 48 ] and surplus of perineurial septae in spinal nerve roots were observed (Figure 3F–J ).…”

Section: Resultssupporting

confidence: 79%

“…Excessive growth of peripheral nerve fibers/Schwann cells was also observed in the autopsy case (# 4), that is, we observed thickened spinal meninges containing neuromatous sprouting of small nerve fascicles resembling the spinal neuroma described in patients with multiple endocrine neoplasia, type 2b MEN2b [ 48 ]. Neuromatous sprouting has not been described in the few autopsies of patients with MPZ ‐neuropathies that have previously been reported [ 60 , 61 , 62 , 63 ].…”

Section: Discussionsupporting

confidence: 71%

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Myelin protein zero mutation‐related hereditary neuropathies: Neuropathological insight from a new nerve biopsy cohort

Bremer,

Meinhardt,

Katona

et al. 2023

Brain Pathology

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Myelin protein zero (MPZ/P0) is a major structural protein of peripheral nerve myelin. Disease‐associated variants in the MPZ gene cause a wide phenotypic spectrum of inherited peripheral neuropathies. Previous nerve biopsy studies showed evidence for subtype‐specific morphological features. Here, we aimed at enhancing the understanding of these subtype‐specific features and pathophysiological aspects of MPZ neuropathies. We examined archival material from two Central European centers and systematically determined genetic, clinical, and neuropathological features of 21 patients with MPZ mutations compared to 16 controls. Cases were grouped based on nerve conduction data into congenital hypomyelinating neuropathy (CHN; n = 2), demyelinating Charcot–Marie‐Tooth (CMT type 1; n = 11), intermediate (CMTi; n = 3), and axonal CMT (type 2; n = 5). Six cases had combined muscle and nerve biopsies and one underwent autopsy. We detected four MPZ gene variants not previously described in patients with neuropathy. Light and electron microscopy of nerve biopsies confirmed fewer myelinated fibers, more onion bulbs and reduced regeneration in demyelinating CMT1 compared to CMT2/CMTi. In addition, we observed significantly more denervated Schwann cells, more collagen pockets, fewer unmyelinated axons per Schwann cell unit and a higher density of Schwann cell nuclei in CMT1 compared to CMT2/CMTi. CHN was characterized by basal lamina onion bulb formation, a further increase in Schwann cell density and hypomyelination. Most late onset axonal neuropathy patients showed microangiopathy. In the autopsy case, we observed prominent neuromatous hyperinnervation of the spinal meninges. In four of the six muscle biopsies, we found marked structural mitochondrial abnormalities. These results show that MPZ alterations not only affect myelinated nerve fibers, leading to either primarily demyelinating or axonal changes, but also affect non‐myelinated nerve fibers. The autopsy case offers insight into spinal nerve root pathology in MPZ neuropathy. Finally, our data suggest a peculiar association of MPZ mutations with mitochondrial alterations in muscle.

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Section: Resultssupporting

confidence: 79%

Section: Discussionsupporting

confidence: 71%

Myelin protein zero mutation‐related hereditary neuropathies: Neuropathological insight from a new nerve biopsy cohort

Bremer,

Meinhardt,

Katona

et al. 2023

Brain Pathology

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“…25 Motor and sensory nerve conduction studies reveal mild impairments and chronic denervation on needle electromyography (EMG). 23,25…”

Section: Endocrine Disordersmentioning

confidence: 99%

“…Hyperplastic interlacing bands of Schwann cells and myelinated fibers that overlie the posterior columns of the spinal cord are reported in postmortem samples. 23 Involvement of autonomic nerves is also reported and leads to severe constipation or diarrhea. 23,24…”

Section: Endocrine Disordersmentioning

confidence: 99%

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Peripheral nerve disease secondary to systemic conditions in children

Wilmshurst

Ouvrier

Ryan

2019

Ther Adv Neurol Disord

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This review is an overview of systemic conditions that can be associated with peripheral nervous system dysfunction. Children may present with neuropathic symptoms for which, unless considered, a causative systemic condition may not be recognized. Similarly, some systemic conditions may be complicated by comorbid peripheral neuropathies, surveillance for which is indicated. The systemic conditions addressed in this review are critical illness polyneuropathy, chronic renal failure, endocrine disorders such as insulin-dependent diabetes mellitus and multiple endocrine neoplasia type 2b, vitamin deficiency states, malignancies and reticuloses, sickle cell disease, neurofibromatosis, connective tissue disorders, bowel dysmotility and enteropathy, and sarcoidosis. In some disorders presymptomatic screening should be undertaken, while in others there is no benefit from early detection of neuropathy. In children with idiopathic peripheral neuropathies, systemic disorders such as celiac disease should be actively excluded. While management is predominantly focused on symptomatic care through pain control and rehabilitation, some neuropathies improve with effective control of the underlying etiology and in a small proportion a more targeted approach is possible. In conclusion, peripheral neuropathies can be associated with a diverse range of medical conditions and unless actively considered may not be recognized and inadequately managed.

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