Neuromyelitis Optica: Atypical Clinical and Neuroradiological Presentation

Introduction

Devic's syndrome or neuromyelitis optica (NMO), characterized by an acute or sub-acute loss of vision in one or both eyes, is caused by an acute optic neuropathy preceded or followed in subsequent weeks to months by ascending or transverse myelitis. It was first described by Allbutt in 1870 and later by Devic in 1894, who defined it as NMO and from whom the disease took its name.

In the case described by us, the medullary onset was followed at a distance of nine years by the appearance of widespread alteration of the white matter without selective involvement of the optic nerves and the age at onset of the syndrome represents the particular features of the case and confirms the extreme variability of the clinical manifestations of NMO.

Case Report

In May 2004, a 64-year-old healthy white woman began to suffer of loss of motor and thermal sensibility in the left lower limb. A few months later she was seen for the first time by a neurologist who required an MRI examination, which showed point and nonspecific areas of abnormal intensity signal on the deep left frontal and right front-parietal white matter in the long TR sequences (DP, T2 and FLAIR). After intravenous administration of contrast medium no areas of pathological enhancement were documented in either the brain or optic nerves. The examination was extended to the study of the spinal cord where T2-weighted images documented a small intramedullary area of altered signal at metameric level C2–C4, for which a diagnosis of post-viral transverse myelitis was considered (Figure 1a). The patient started cortisone therapy with a subsequent complete remission of symptoms.

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Figure 1.

a) MRI exam of the spinal cord performed in 2004 documented, on T2-weighted images, the presence of a small not well defined intramedullary area of altered signal at metameric level C2–C4. b) The same exam performed in 2013 confirmed the signal alteration.

Exactly one year later, the patient returned to our department for the sudden onset of visual and motor disorders, and more specifically, blurred vision of the left eye with intermittent loss of vision. MRI of the brain and spinal cord showed no significant changes compared to the previous examination (Figure 2a). This finding led us therefore to hypothesize NMO. Again the patient was treated with cortisone therapy resulting in a complete remission of symptoms.

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Figure 2.

a) MRI exam performed in 2005, showed in the long TR sequences the presence of point and nonspecific areas of abnormal intensity signal on the deep left frontal and right front-parietal white matter, b) In 2013, after 9 years, MRI of the brain showed, in the long TR sequences, a widespread alteration of signal of the biemisferical subcortical and deep white matter with extensive involvement of the white matter.

In 2013, nine years later, the patient presented a reappearance of the visual and motor disorders. Long TR MRI sequences of the brain showed a widespread signal alteration of the bihemispherical subcortical and deep white matter with extensive involvement of the white matter of the bridge, cerebellar peduncles and cerebellar bilaterally without, however, areas of pathological enhancement after intravenous administration of contrast medium (Figure 1b–2b).

At this point, the neurologist decided to investigate search for circulating IgG antibodies against aquaporin 4 (AQP4); the data obtained showed an IgG positivity, thus confirming the diagnosis of NMO.

In this case, compared to a clinical presentation of atypical deficit neurological involvement, the neuroradiological findings of a progressive diffuse involvement of the white matter were atypical results.

Discussion

Neuromyelitis optica (NMO) usually tends to affect children or young adults. The average age at onset of symptoms is around 40 years, but all ages can be affected; it has a higher prevalence in females (F: M = 9:1).

There is a higher prevalence of this condition in Western countries but Japan is the country with the highest proportion of NMO patients.^1–2

The majority of patients do not suffer from other diseases, but an association with other clinical conditions, such as SLE or pulmonary tuberculosis, has been reported.^3–4 The differential diagnosis should first include multiple sclerosis, which is the prime demyeli-nating disease, caused by an oligodendrocyte disorder, with acute disseminated encephalomyelitis (ADEM), disseminated lupus erythematous (SLE) or Sjögren's syndrome.^5–10

NMO is an idiopathic inflammatory disease of the central nervous system, episodically affecting the optic nerves and spinal cord. It is characterized by destruction of the myelin sheath, in association with areas of necrosis, cavity formation, small areas of perivascular lymphocytosis and in moderately advanced cases the formation of glial tissue. ¹¹

From a clinical point of view NMO usually presents with temporary blindness, occasionally permanent, unilateral or bilateral, associated with optic neuritis or retrobulbar neuritis. It can also lead to various degrees of muscle weakness or paralysis of the upper and/or lower extremities, numbness or bladder and/or the intestinal dysfunction in the case of spinal cord involvement.^12–15

There are two main types of NMO: the first in which optical and spinal disorders occur at intervals (days or weeks), the second in which these episodes occur after months or years.

No brain alterations can been seen at MRI in the early disease stages, but later white matter lesions may appear, thus entering the differential diagnosis with MS.^16–18 At spinal level, however, the typical appearance of NMO is a hyperintense lesion with a longitudinal extension of at least three vertebral segments. ¹⁹

While at first NMO was thought to be a subtype of MS, nowadays an IgG has been found in the serum of patients that binds selectively to AQP4, the target antigen of this antibody-mediated disease. AQP4, present on the membranes of astrocyte cells, is a protein of the water channels that plays a vital role in the liquid homeostasis of the central nervous system. AQP4 is present throughout the brain tissue but is most prevalent on the optic nerves and spinal cord.

The mechanism by which AQP4 acts as a cause of NMO is not yet entirely clear. It is thought to initiate a complement-dependent cytotoxic astrocyte mechanism, leading to leukocyte infiltration, cytokine release and an interruption of the blood-brain barrier resulting in oligodendrocyte death, loss of myelin and neuronal death, as described by Wingerchuk et al. ²⁰ . There is no typical treatment for NMO: many studies were done on plasma exchange and immunosuppressive/immunomodulatory drugs. Now many new therapeutic strategies are being proposed for the treatment of NMO, such as new monoclonal antibodies targeting CD20 B lymphocytes and complement, two factors implicated in this pathology.

Many cases have been reported in the literature of NMO associated with several clinical conditions and confirmed or not by MRI. Nakano et al. ²¹ and Takayama et al. ²² reported cases of optic neuritis associated with ileus and inappropriate secretion of antidiuretic hormone. Yoon et al. determined the frequency of high IgE values in the blood in idiopathic myelitis featuring common clinical and laboratory profiles with MRI findings. ²³ There have been cases of NMO associated with myocarditis and diffuse oedema of the pelvis. ²⁴ Acute optic neuritis followed by cervical transverse myelitis was described in a 16-year-old patient with pemphigus foliaceus. ²⁵ Oh et al. presented a case of a young woman with a tumour lesion in the spinal cord advising and planning the surgical excision. Intraoperatively no tumour masses were found and in the end a diagnosis of NMO was given. ²⁶ Finally, Landragin et al. presented a case of a patient who years after the onset of the first symptoms showed a bilateral optic neuritis with atrophy of the spinal cord. ²⁷ The cases presented in literature emphasize the great variability of clinical and radiological appearance of this pathology and our case shows the possibility that spine involvement may precede the clinical manifestations suggestive of NMO by many years.^28–30 In fact, in the case presented in this paper the diagnosis was made only nine years after her first clinical presentation and the first MRI of spine by CSF study with IgG antibody against AQP4.

In conclusion, the onset and progression of NMO shows such extreme variability of clinical and MRI findings that we need to put the suspicion of Devic's disease in any atypical MR presentation of spinal cord lesion with or without clinical presentation of a vision problem. These patients should have a CSF study for IgG antibody against AQP4 to check the diagnosis of NMO.