Review ArticleAutoimmune and paraneoplastic movement disorders: An update
Introduction
The discovery of a variety of antibodies over the past few decades has helped to characterize the clinical syndromes of several autoimmune disorders of the nervous system. Movement disorders (MDs) are observed in many of these entities and its subacute onset is often a clue for the diagnosis. In this review, we discuss recent advances in these disorders. We excluded MDs within the spectrum of demyelinating disorders such as multiple sclerosis, and neurodegenerative disorders such as Parkinson's disease in which autoimmunity has been proposed to play a role [1], [2].
Section snippets
Sydenham's chorea
Sydenham's chorea (SC) is a childhood-onset, delayed manifestation of GABHS infection and a major component of rheumatic fever (RF). Chorea presents in about 26% of patients with RF [3], it is usually asymmetrical, although pure hemichorea is observed in about 20% of cases; associated severe hypotonia presents in about 8% of cases leading to bedridden, a condition known as: “chorea paralytica”. Other motor phenomena include motor impersistance (“milkmaid's grip” and “darting tongue”), phonic or
Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis
Anti-NMDAR-encephalitis is considered the most common autoimmune encephalitis. It affects predominantly young individuals with a mean age at onset of 23 years; women are affected 4 times more frequently than men, but female predominance is less prominent in individuals younger than 12 years and older than 45 years [16]. A substantial proportion of young females with NMDAR-encephalitis have underlying ovarian teratomas, but also various carcinomas have been reported, especially in adults. The
Stiff-person syndrome
Stiff-person syndrome (SPS) is the classical presentation of autoimmune disorders associated with antibodies against the enzyme GAD [46]. Most cases present between the fourth and sixth decade of life (although SPS has been also described in children), and women outnumber men 5 to 1.
The disorder is characterized by increased tone of axial and limb muscles, with superimposed muscle spasms leading to lumbar hyperlordosis (Fig. 1), impaired gait and falls [46], [47]. Dysautonomic crisis with
Systemic lupus erythematosus and antiphospholipid syndrome
Chorea is the most frequent MD observed in SLE and APS with prevalence between 1% and 3%, and it may be the initial presentation, even before patients fulfill all diagnostic criteria for SLE or APS [5], [58]. Women represent > 90% of cases with a median age at onset between 15 and 26 years. The movements usually coexist with neuropsychiatric manifestations such as abnormal behavioral or frank psychosis [58]. PET scans using 18F-deoxyglcose have shown increased metabolism in the contralateral
Hashimoto's encephalopathy (SREAT)
Hashimoto's encephalopathy (HE) also known as “SREAT” is defined by the combination of neuropsychiatric symptoms, laboratory evidence of anti-thyroid antibodies and prominent clinical improvement with steroids along with lack of evidence of other disorders. Onset is usually between 45 and 55 years of age, and females are 5 times more commonly affected. Patients usually have high titers of anti-thyroid peroxidase antibodies; however, most patients are euthyroid or have subclinical hypothyroidism;
Paraneoplastic movement disorders
Cerebellar ataxia is the MD most commonly presenting as a classic paraneoplastic neurological syndrome (PNS) and is associated with a variety of antibodies including: ANNA-1 (anti-Hu), ANNA-2 (anti-Ri), PCA-1(anti-Yo), PCA-2, PCA-Tr, ZIC4, or the so-called “medusa head ataxia” antibodies; small-cell carcinoma of the lungs (SCLC) is the most commonly detected cancer [71]. These patients usually have a much rapid course than those with other forms of autoimmune cerebellar ataxia, with poor
Clinical approach and diagnosis
An autoimmune pathogenesis should be suspected in patients with acute or subacute onset of MDs usually followed by rapid progression and accompanied neurological manifestations such as psychiatric manifestations, brainstem dysfunction, dysautonomia or frank encephalitis. Fluctuant neurological manifestations may be observed in patients with PERM; paroxysmal dizziness spells have been recently recognized in those with LGI1 antibodies [26], and “brainstem attacks” may precede the onset of GAD
Therapy
Symptomatic therapy should be provided for most patients, the selection of pharmacology agents depends on the underlying phenomenology (Fig. 2 and Table 3). Treatment of an underlying cancer with tumor removal or chemotherapy may ameliorate the involuntary movements. Although this is less common in patients with onconeural antibodies, directed to intracellular proteins, where a prominent role of lymphocyte-T autoimmunity is present, tumor removal is of major importance in patients with ovarian
Conclusions
An autoimmune etiology is part of the differential diagnosis of practically the whole spectrum of MDs in patients of all ages and both genders, particularly when the course is acute or subacute. The phenomenological presentation of the MDs, along with associated neurological and medical manifestations, should be a diagnostic clue. In all the autoimmune MDs early recognition should rapidly lead to institution of treatment with immunosuppressive drugs and symptomatic therapy to improve the
Acknowledgement
No funding was provided for this study. We wish to thank the National Parkinson Foundation for their support to our Center of Excellence.
Author roles
1) Research project: A. Conception, B. Organization, C. Execution; 2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; 3) Manuscript: A. Writing of the first draft, B. Review and Critique.
José Fidel Baizabal-Carvallo: 1A, 1B, 1C, 3A,3B.
Joseph Jankovic: 1A, 1B, 1C, 3B.
Financial disclosure/conflict of interest concerning the research related to the manuscript
None for both authors.
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