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Peripheral Neuropathy

Chapter 457 | Harrison's 22e

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[PAGE 3594] 3594 PART Neurologic Disorders another chronic inflammatory disorder such as vasculitis, sarcoidosis, abnormalities, basal ganglia or cortical gray matter lesions, and gado- or lymphoma. Many cases previously thought to represent ADEM are linium enhancement of all abnormal areas. In contrast, OCBs in the now recognized as MOGAD. The hallmark of ADEM is the presence CSF are more common in MS. In one study of adult patients initially of widely scattered foci of perivenular inflammation and demyelin- thought to have ADEM, 30% experienced additional relapses over a ation that can involve both white matter and gray matter structures, in follow-up period of 3 years, and they were reclassified as having MS. contrast to larger confluent white matter lesions typical of MS. In the Other patients initially classified as ADEM are subsequently found to most explosive form of ADEM, acute hemorrhagic leukoencephalitis, have NMO, MOGAD, or GFAP autoimmunity. Occasional patients the lesions are vasculitic and hemorrhagic, and the clinical course is with “recurrent ADEM” have also been reported, especially children; devastating. however, it is not possible to distinguish this entity from atypical MS. Postinfectious encephalomyelitis is most frequently associated with Because of the clinical overlap at presentation between ADEM and MS, the viral exanthems of childhood. Infection with measles virus is it is important that routine surveillance imaging be performed follow- the most common antecedent (1 in 1000 cases). Worldwide, measles ing recovery from ADEM so that subclinical disease activity due to MS encephalomyelitis is still common, although use of the live measles can be recognized and treatment for MS initiated. vaccine has dramatically reduced its incidence. In developed countries, ADEM is now most frequently associated with varicella (chickenpox) I TREATMENT infections (1 in 4000–10,000 cases). It may also follow infection with Initial therapy is with high-dose glucocorticoids; depending on the rubella, mumps, influenza, parainfluenza, Epstein-Barr virus, human response, treatment may need to be continued for 8 weeks. Patients herpesvirus-6, HIV, dengue, Zika, other viruses, and Mycoplasma who fail to respond within a few days may benefit from a course of pneumoniae. Cases have also been described in association with SARS- plasma exchange or IV immunoglobulin. The prognosis reflects the CoV-2 infection. Some patients may have a nonspecific upper respira- severity of the underlying acute illness. In modern case series of pre- tory infection or no known antecedent illness. Modern vaccines appear sumptive ADEM in adults, mortality rates of 5–20% are reported, and to pose no meaningful risk for ADEM; one large study (Vaccine Safety many survivors have permanent neurologic sequelae. Datalink) of 24 different vaccines in >9 million individuals (64 million FURTHER READING doses in total) revealed no excess risk for ADEM, with the possible Banwell B et al: Diagnosis of myelin oligodendrocyte glycoprotein exception of Tdap (tetanus, diphtheria, acellular pertussis) vaccine antibody-associated disease: International MOGAD Panel proposed estimated at less than one case per million doses. criteria. Lancet Neurol 22:268, 2023. All forms of ADEM presumably result from a cross-reactive Baxter R et al: Acute demyelinating events following vaccines: A case- immune response to the infectious agent that then triggers an inflam- centered analysis. Clin Infect Dis 63:1456, 2016. matory demyelinating response. Autoantibodies to MBP and other Cacciaguerra L et al: Updates in NMOSD and MOGAD diagnosis myelin antigens have been detected in the CSF from some patients with and treatment: A tale of two central nervous system autoimmune ADEM, and as noted above, ADEM cases with serum or CSF antibod- inflammatory disorders. Neurol Clin 42:77, 2024. ies against MOG are now considered to be MOGAD. Cree BAC et al: Inebilizumab for the treatment of neuromyelitis optica CLINICAL MANIFESTATIONS spectrum disorder (N-MOmentum): A double-blind, randomised placebo-controlled phase 2/3 trial. Lancet 394:1352, 2019. In severe cases, onset is abrupt and progression rapid (hours to days). Hagbohm C et al: Clinical and neuroimaging phenotypes of autoim- In postinfectious ADEM, the neurologic syndrome generally begins mune glial fibrillary acidic protein astrocytopathy: A systematic late in the course of the viral illness as the exanthem is fading. Fever review and meta-analysis. Eur J Neurol 20:e16284, 2024. reappears, and headache, meningismus, and lethargy progressing to Pittock SJ et al: Eculizumab in aquaporin-4-positive neuromyelitis coma may develop. Seizures are common. Signs of disseminated neu- optica spectrum disorder. N Engl J Med 381:614, 2019. rologic disease are consistently present (e.g., hemiparesis or quadripa- Qin C et al: Single-cell analysis of anti-BCMA CAR T cell therapy in resis, extensor plantar responses, lost or hyperactive tendon reflexes, patients with central nervous system autoimmunity. Sci Immunol sensory loss, and brainstem involvement). In ADEM due to chicken- 9:eadj9730, 2024. pox, cerebellar involvement is often conspicuous. CSF protein is mod- Traboulsee A, et al. Safety and efficacy of satralizumab monotherapy estly elevated (0.5–1.5 g/L [50–150 mg/dL]). Lymphocytic pleocytosis, in neuromyelitis optica spectrum disorder: A randomised, double- generally ≥ 200 cells/ µ L, occurs in 80% of patients. Occasional patients blind, multicentre, placebo-controlled phase 3 trial. Lancet Neurol have higher counts or a mixed polymorphonuclear-lymphocytic pat- 19:402, 2020. tern during the initial days of the illness. Transient CSF oligoclonal Wingerchuk DM et al: International consensus diagnostic criteria for banding was reported in a minority of cases. MRI usually reveals neuromyelitis optica spectrum disorders. Neurology 85:177, 2015. extensive changes in the brain and spinal cord, consisting of white matter hyperintensities on T2 and fluid-attenuated inversion recovery (FLAIR) sequences with gadolinium enhancement on T1-weighted sequences. DIAGNOSIS The diagnosis is most reliably established when there is a history of a recent infectious illness. In severe cases with predominantly cerebral Section 3 Nerve and Muscle Disorders involvement, acute encephalitis due to infection with herpes simplex or other viruses including HIV may be difficult to exclude; other consid- erations include hypercoagulable states including the antiphospholipid 457 Peripheral Neuropathy antibody syndrome, autoimmune (paraneoplastic) limbic encephalitis, vasculitis, sarcoidosis, primary CNS lymphoma, or metastatic cancer. An explosive presentation of MS can mimic ADEM, and especially in Anthony A. Amato, Richard J. Barohn adults, it may not be possible to distinguish these conditions acutely. The simultaneous onset of disseminated symptoms and signs is com- mon in ADEM and rare in MS. Similarly, meningismus, encephalopa- Peripheral nerves are composed of sensory, motor, and autonomic thy (drowsiness, stupor or coma), and seizures suggest ADEM rather elements. Diseases can affect the cell body of a neuron or its periph- than MS. Unlike MS, in ADEM, optic nerve involvement is generally eral processes, namely the axons or the encasing myelin sheaths. bilateral and transverse myelopathy complete. MRI findings that Most peripheral nerves are mixed and contain sensory and motor as favor ADEM include extensive and relatively symmetric white matter well as autonomic fibers. Nerves can be subdivided into three major [PAGE 3595] Peripheral Neuropathy 3595 CHAPTER 457 classes: large myelinated, small myelinated, and small unmyelin- I INFORMATION FROM THE HISTORY AND ated. Motor axons are usually large myelinated fibers that conduct PHYSICAL EXAMINATION: SEVEN KEY rapidly (~50 m/s). Sensory fibers may be any of the three types. QUESTIONS (TABLE 457-1) Large-diameter sensory fibers conduct propri