Clinical Features
The incidence of NMO is highest during the third to fourth decade of life, with a very strong female preponderance. Interestingly, the female/male ratio is 1:1 in monophasic NMO (no evidence of recurrence within 3 years of the index events of bilateral AON and TM), but 5:1 in the relapsing form of NMO. Compared to MS, which has a predilection for Caucasian patients, NMO appears to affect all racial groups [17-23]. On average, NMO patients are 10 years older than MS patients, with a median age of onset of 39 years [23, 24].
Various autoimmune diseases often coexist with NMO, the most common of which are systemic lupus erythematosus (SLE), autoimmune thyroid disease, and Sjogren’s syndrome (SS) [23]. The frequency of concomitant autoimmune disease ranges from 10 to 40% [23]. Since patients with NMO may experience symptoms of a concomitant systemic autoimmune disease (e.g., sicca symptoms, rash, alopecia, photosensitive rash, arthritis), the presence of such symptoms does not militate against, but, in fact, supports the diagnostic suspicion of NMO. Furthermore, it is important to note that CNS complications of systemic autoimmune diseases are infrequent (e.g., seizures and psychosis in SLE). Therefore, in patients with typical neurologic manifestations of NMO, and who exhibit NMO-IgG seropositive, the “working” diagnosis of NMO can be confirmed expeditiously, with a high degree of confidence, and most particularly in the patient with a second, concomitant autoimmune disease. In such circumstances, moving rapidly (after achieving full control of the acute inflammatory “ictus”) to implement an appropriate disease-modifying strategy is strongly encouraged (“time is tissue”).
Severe AON or recurrent isolated AON should raise suspicion for NMO, particularly in the absence of brain MRI lesions typical of MS [23]. MS-related AON typically causes central visual blurring associated with impaired color vision (dyschromatopsia), retrobulbar pain that is exacerbated by eye movement, phos- phenes, and visual deterioration with heat exposure (Uhthoff’s phenomenon) [25, 26]. Bilateral simultaneous AON is exceedingly rare in MS and is strongly suggestive of NMO; conversely, unilateral AON is less common with (but does not rule out) NMO [27-29]. NMO-associated AON also typically results in more severe visual loss with a poor prognosis for recovery, compared to MS [25, 30, 31]. In fact, at 5 years from disease onset, 41% of NMO patients will suffer monocular or binocular blindness [29].
In MS, acute TM typically results in sensory manifestations [32, 33]. Acute TM in NMO commonly culminates in more devastating neurologic deficits, including paralysis, sensory loss, and bladder and bowel involvement below the level of the lesion [32]. Furthermore, the MRI often reveals longitudinally extensive TM (LETM) in NMO that involves most of the axial thickness of the spinal cord, in contradistinction to the longitudinally limited lesions in MS that only affect part of the spinal cord (typically the dorsal columns) [32]. The spinal cord MRI characteristics of NMO are discussed later. Lhermitte’s phenomenon and paroxysmal tonic spasms are common manifestations of NMO and, interestingly, portend a relapsing rather than monophasic course of the disease [23, 34]. Radicular pain is also much more common in NMO compared to MS [35].
Intractable vomiting or hiccups (resulting from medullary lesions affecting the area postrema and nucleus tractus solitarius) are a common brainstem syndrome of NMO, affecting about 20% of patients [36, 37]. About 17% of NMO patients have been reported to suffer from persistent hiccups [36]. In our experience, this so- called area postrema syndrome often compels referrals to the gastroenterology service and is often mistakenly diagnosed as gastroparesis, despite unremarkable gastric emptying studies.
A far more ominous and potentially lethal manifestation of medullary involvement in NMO is neurogenic respiratory failure [34]; respiratory failure is distinctly rare in MS and almost always occurs in the setting of advanced MS with severe disability rather than in the acute or early phases of the disease [23].
Various brainstem ocular motor abnormalities (including upbeat nystagmus, downbeat nystagmus, vestibular nystagmus, and opsoclonus-myoclonus syndrome) have been reported in NMO; consistent with a brainstem localization, these patients also experienced concomitant pyramidal tract dysfunction as well as other cranial neuropathies [38]. Sensorineural hearing loss has also been reported in NMO, most probably due to brainstem involvement [39].
Diencephalic lesions can often lead to manifestations like the syndrome of inappropriate antidiuretic hormone secretion (SIADH), narcolepsy, thermodysregula- tion, anorexia or other eating disorders [8, 40-43]. In contradistinction, such lesions in MS are infrequent [44].
NMO may also cause other manifestations, albeit rarely. Myopathy with elevated creatine kinase levels and muscle pain and nonspecific fatigue have been reported [45, 46]. Encephalopathy (which may be part of the posterior reversible encephalopathy syndrome [PRES]) has also been described in the disease [23, 47].
