ORIGINAL CONTRIBUTION Adult-Onset - Syndrome

James P. Klaas, MD; J. Eric Ahlskog, PhD, MD; Sean J. Pittock, MD; Joseph Y. Matsumoto, MD; Allen J. Aksamit, MD; J. D. Bartleson, MD; Rajeev Kumar, MD; Kathleen F. McEvoy, MD, PhD; Andrew McKeon, MD

Background: Little is known about adult-onset opso- , 1); a parainfectious cause was assumed in the re- -myoclonus syndrome (OMS) outside of indi- mainder of the patients. Follow-up of 1 month or more vidual case reports. was available for 19 patients (median, 43 months; range, 1-187 months). Treatment (median, 6 weeks) consisted Objective: To describe adult-onset OMS. of immunotherapy and symptomatic therapy in 16 pa- tients, immunotherapy alone for 2, and clonazepam alone Design: Review of medical records (January 1, 1990, for 1. Of these 19 patients, OMS remitted in 13 and im- through December 31, 2011), prospective telephone sur- proved in 3; 3 patients died (neurologic decline, 1; can- veillance, and literature review (January 1, 1967, through cer, 1; and myocardial infarction, 1). The cause of death December 31, 2011). was of paraneoplastic origin in 60 of 116 literature re- view patients, with the most common carcinomas being Setting: Department of , Mayo Clinic, Roch- lung (33 patients) and breast (7); the most common an- ester, Minnesota. tibody was antineuronal nuclear type 2 (anti- Ri, 15). Other causes were idiopathic in origin, 38 pa- Patients: Twenty-one Mayo Clinic patients and 116 pre- viously reported patients with adult-onset OMS. tients; parainfectious, 15 (human immunodeficiency virus, 7); toxic/metabolic, 2; and other autoimmune, 1. Both Main Outcome Measures: Clinical course and lon- patients with N-methyl-D-aspartate receptor antibody had gitudinal outcomes. encephalopathy. Improvements were attributed to im- munotherapy alone in 22 of 28 treated patients. Results: The median age at onset of the 21 OMS pa- tients at the Mayo Clinic was 47 years (range, 27-78 years); Conclusions: Adult-onset OMS is rare. Paraneoplastic 11 were women. Symptoms reported at the first visit in- and parainfectious causes (particularly human immu- cluded dizziness, 14 patients; balance difficulties, 14; nau- nodeficiency virus) should be considered. Complete re- sea and/or vomiting, 10; vision abnormalities, 6; / mission achieved with immunotherapy is the most com- tremulousness, 4; and altered speech, 2. Myoclonus mon outcome. distribution was extremities, 15 patients; craniocervi- cal, 8; and trunk, 4. Cancer was detected in 3 patients Arch Neurol. 2012;69(12):1598-1607. Published online (breast adenocarcinoma, 2; and small cell lung carci- September 17, 2012. doi:10.1001/archneurol.2012.1173

PSOCLONUS-MYOCLONUS known5,6). However, there are few col- syndrome (OMS) is well lated data to inform physicians about described in children which common and uncommon causes (also known as Kins- should be considered, the clinical course, bourne syndrome1), usu- and outcomes from treatment.7 We ally occurring as a paraneoplastic neuro- describe OMS in adults consecutively O 1,2 logic accompaniment of evaluated at Mayo Clinic, Rochester, Min- nesota, during a 21-year period and pro- spectively evaluated for longitudinal out- Author Affiliations: Video available online at Author Affil www.archneurol.com comes. We also evaluated the 40-year Departments of Neurology cumulative literature on adult-onset OMS. Departments (Drs Klaas, Ahlskog, Pittock, Klaas, Ahlsk Matsumoto, Aksamit, Bartleson, with long-term neurologic, behavioral, and Matsumoto, 3,4 McEvoy, and McKeon) and developmental sequelae. The OMS lit- METHODS McEvoy, and Laboratory Medicine and erature on adults is largely confined to Laboratory M Pathology (Drs Pittock and cases and small case series. Most clini- Pathology (D We conducted a medical record review, fol- McKeon), Mayo Clinic College cians know that a paraneoplastic cause McKeon), M of Medicine, Rochester, low-up telephone interview, and serologic of Medicine, Minnesota; and Colorado should be considered (eg, antineuronal evaluation of patients with adult-onset OMS Minnesota; a Neurological Institute nuclear antibody type 2 [ANNA-2; anti- (age at onset, Ն18 years and initial examina- Neurological Movement Disorders Center, Ri] and accompanying breast adenocarci- tion findings predominated by opsoclonus and Movement D Englewood (Dr Kumar). noma or small cell carcinoma are well myoclonus) seen at the Mayo Clinic, Roches- Englewood (

ARCH NEUROL / VOL 69 (NO. 12), DEC 2012 WWW.ARCHNEUROL.COM 1598

©2012 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 ter, from 1990 to 2011. The study was approved by the Mayo RESULTS Clinic Institutional Review Board (10-007942).

MAYO CLINIC PATIENT ASCERTAINMENT MAYO CLINIC PATIENTS

The Mayo Clinic medical records linkage system was retro- Demographics and Clinical Features spectively queried using the terms opsoclonus and Kinsbourne syndrome to identify adult patients who received a diagnosis We identified 21 Mayo Clinic patients (11 women and of OMS at the Mayo Clinic between 1990 and 2011. 10 men) with adult-onset OMS who met the inclusion criteria. Median follow-up was 43 months (range, 1-187 INCLUSION CRITERIA months). The median age at symptom onset was 47 years (range, 27-78 years). Medical records for 91 patients were reviewed by 2 of the au- A flulike prodrome before neurologic symptom thors (J.P.K. and A.M.). We included patients with simulta- onset was reported by 6 patients. The initial neurologic neous onset of opsoclonus and myoclonus at or after age 18 symptoms included dizziness, 14 patients (67%); years, with OMS being the predominant clinical presentation. balance difficulties (caused by myoclonus), 14 Seventy patients were excluded: 37 pediatric patients with symp- (67%); nausea and/or vomiting, 10 (48%); vision abnor- toms persisting into adulthood, 23 patients determined to have malities (caused by opsoclonus), 6 (28%); tremor/ final neurologic diagnoses other than OMS, 3 patients with only tremulousness, 4 (19%); and altered speech (caused by opsoclonus identified on examination, 2 patients with only my- oclonus identified on examination, 4 patients for whom not myoclonus), 2 (10%). Symptoms progressed rapidly, enough data were available, and 1 patient with opsoclonus and and most patients were seen by a neurologist within a myoclonus observed as part of a more widespread encepha- median of 4 weeks after symptom onset. Levels of litic disorder. The latter patient’s case has been published8 and mobility at nadir for 18 patients were wheelchair or is included in the current literature review. 2-person assistance needed to mobilize, 10 patients; gait In addition to documenting clinical information from the unsteadiness but able to walk independently, 6; and medical records, we attempted to contact all 21 included pa- cane required to walk independently, 2. Other symp- tients by telephone for additional longitudinal information re- toms that developed included weight loss (Ͼ4.5 kg), 10 garding the clinical course of the disease. For patients who had patients; mood changes, 9 (depression, 5; irritability/ died, additional information regarding the cause of death was emotional lability, 4); dysphagia, 3 (resulting from obtained by review of the death certificate, when available. myoclonus or nausea/vomiting); fatigue/sleep distur- bance, 3; , 1; and falls, 1. SEROLOGIC EVALUATION All 21 patients were examined by a Mayo Clinic staff neurologist. Myoclonus (sudden, brief, shock-like, in- For each patient, a serum sample was evaluated, as previously voluntary movements) was identified on clinical exami- described, by (1) standardized immunofluorescence criteria for nation in all 21 patients (Table 1). Opsoclonus, being IgG neural autoantibodies (ANNA-1 [also known as anti-Hu], the ocular manifestation of myoclonus, was present in -2, -3; amphiphysin antibody, Purkinje cell cytoplasmic anti- all patients. The myoclonus was typically posture- or body [PCA] type 1 [also known as anti-Yo], -2, and Tr anti- movement-induced (action myoclonus), including 3 pa- bodies; collapsin-response mediator-protein [CRMP] 5 IgG, tients with lower extremity myoclonus that was present antiglial/neuronal nuclear antibody [AGNA-1], N-methyl-D- aspartate [NMDA] receptor antibody, ␥-aminobutyric acid B or worse on standing, which caused unsteadiness, tremu- [GABA-B] receptor antibody, and ␣-amino-3-hydroxyl-5- lousness, and falls. Anatomic distribution of myoclonus methyl-4-isoxazole-propionate [AMPA] receptor antibody); (2) on examination was extremities, 15 patients (upper and by radioimmunoprecipitation assays for targeting neu- lower, 13; upper only, 1; and lower only, 1); craniocer- ronal voltage-gated cation channels (neuronal voltage-gated po- vical, 8 (hyperkinetic dysarthria, 5; and head, 3); and tassium channel [VGKC] complex, calcium channels [P/Q- trunk, 4. Additional neurologic findings were reported ␣ ␣ type and N-type], muscle [ 1] and neuronal [ 3] ganglionic in 3 patients as brisk, deep tendon reflexes. nicotinic acetylcholine receptors) and glutamic acid decarbox- ylase 65-isoform (GAD65); (3) by human embryonic kidney Evaluations transfected cell-binding assays for antibodies targeting NMDA, AMPA, and GABA-B receptors and VGKC complex proteins (dis- Findings from magnetic resonance imaging, performed integrin and metalloproteinase 22 [ADAM22] and a soluble bind- ing partner of ADAM22, leucine-rich, glioma-inactivated 1 in 20 patients, were unremarkable in all but 1 patient with [LGI1] protein) (Euroimmun); and (4) by recombinant West- small-cell lung carcinoma who had metastatic lesions in ern blot analysis for CRMP-5-IgG.9-16 both cerebellar hemispheres and in the right caudate nucleus (patient 7). Cerebrospinal fluid (CSF) analysis LITERATURE REVIEW PATIENTS was available for 18 patients (86%) (Table 1) and re- vealed elevated protein (Ͼ45 mg/dL) in 11 patients (me- We searched PubMed using the terms opsoclonus and myoclonus dian, 64 mg/dL; range, 47-137 mg/dL), elevated white blood cell count (Ͼ5/␮L) in 9 patients (median, 20/␮L; to identify case reports and case series reporting on patients aged ␮ 18 years or older with OMS or who had opsoclonus and myo- range, 8-94/ L; all lymphocyte predominant), elevated clonus as part of a more widespread disorder. We included all IgG index (Ͼ0.85) in 4 patients (median, 1.14; range, English-language publications identified between 1967 and 2011 0.88-1.64), and CSF-exclusive oligoclonal bands (Ͼ3) with complete descriptions of individual patients. in 5 patients (median, 5; range, 4-8).

ARCH NEUROL / VOL 69 (NO. 12), DEC 2012 WWW.ARCHNEUROL.COM 1599

©2012 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 Table 1. Demographic and Clinical Data for 21 Adults With Opsoclonus-Myoclonus Syndrome

Patient No./ Coexisting Sex/Age, y, Initial Distribution Additional Autoimmune at Onset Symptoms of Myoclonus Symptoms Disorder CSF Findingsa Cancer 1/F/68 D, B, N U 0 0 C, 14/␮L (94% lymphocytes) 0 P, 51 mg/dL IgG index,0.88 2/F/53 D, B L 0 0 NA Primary adenocarcinoma of the breast, infiltrative ductal type, detected after neurologic symptoms, treated surgically 3/M/46 B, V All Fatigue/sleep 0 C, 37/␮L (77% lymphocytes) 0 issues P, 45 mg/dL Paraneoplastic negative 4/F/40 D, N All Weight loss Psoriasis C, 94/␮L (91% lymphocytes) 0 P, 85 mg/dL OCBs, 4 Paraneoplastic negative 5/M/48 B, V, S Cr Weight loss, dysphagia, 0C,Ͻ1/␮L 0 mood changes P, 43 mg/dL 6/F/36 N, V, T/T All, Cr Weight loss, depression 0 C, 8/␮L (91% lymphocytes) 0 P, 45 mg/dL IgG index, 0.90 7/M/54 D, N All, T Weight loss 0 C, 2/␮L (92% lymphocytes) Small-cell lung cancer, brain P, 64 metastasis Paraneoplastic negative 8/M/27 T/T All Mood changes, 0C,3/␮L (72% lymphocytes) 0 weight loss P, 97 mg/dL 9/F/70 D All Weight loss 0 C, 5 (85% lymphocytes) 0 P, 43 mg/dL Paraneoplastic negative 10/F/48 B, D, S Cr Fatigue/sleep issues, 0C,3/␮L (97% lymphocytes) Intraductal breast carcinoma falls, mood changes, P, 29 mg/dL weight loss Paraneoplastic negative 11/M/78 B All, Cr, T Mood changes, 0C,5/␮L 0 weight loss P, 137 mg/dL Paraneoplastic negative 12/F/46 D, B All Mood changes 0 NA 0 13/M/34 D, B, V, N Cr 0 0 C, 1/␮L (90% lymphocytes) 0 P, 47 mg/dL 14/F/32 B, V, N Cr 0 0 C, 20 (95% lymphocytes) 0 P, 26 15/F/47 D, B, N, All 0 0 C, 64/␮L (83% lymphocytes) 0 T/T P, 49 mg/dL OCBs, 5 IgG index, 1.64 Paraneoplastic negative 16/M/44 D, B, V All Fatigue/sleep issues, 0C,8/␮L (95% lymphocytes) 0 weight loss P, 47 mg/dL OCBs, 7 Paraneoplastic negative 17/F/30 D, B, N Cr 0 0 C, 8 (94% lymphocytes) 0 P, 49 mg/dL Paraneoplastic negative 18/M/37 D, B Cr 0 0 NA 0 19/M/52 D, N All, T Weight loss 0 C, 4/␮L (95% lymphocytes) 0 P, 81 mg/dL OCBs, 4 Paraneoplastic negative 20/M/51 D, N All Mood changes 0 C, 4/␮L 0 P, 97 mg/dL Paraneoplastic negative 21/F/52 B, T/T All, T 0 0 C, 38/␮L (89% lymphocytes) 0 P, 42 mg/dL OCBs, 8 IgG index, 1.37 Paraneoplastic negative

Abbreviations: All, all extremities; B, balance difficulties; C, white blood cell count; Cr, craniocervical; CSF, cerebrospinal fluid; D, dizziness; L, lower limbs only; N, nausea and vomiting; NA, not available; OCBs, CSF-exclusive oligoclonal bands; P, protein; S, altered speech; T, trunk; T/T, tremor/tremulousness; U, upper limbs only; V, vision abnormalities. a The CSF reference values were P, Ͼ45 mg/dL; C, Ͼ5/␮L; IgG index, Ͻ0.85; OCBs, Ͼ3.

ARCH NEUROL / VOL 69 (NO. 12), DEC 2012 WWW.ARCHNEUROL.COM 1600

©2012 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 Results of paraneoplastic antibody evaluations in se- set was 50 years (range, 19-80 years); 70 patients (60%) rum (all patients) and CSF (12 patients) were negative. were women. Evidence for a parainfectious source was sought in all but Opsoclonus-myoclonus syndrome was present in iso- 3 patients (2 had a paraneoplastic cause established early lation in 83 patients and accompanied another neuro- in the workup). for which testing was per- logic or neuropsychiatric disorder in 33 patients. Coex- formed in 18 patients (serum, 13; CSF, 13) included Ep- isting disorders were mild behavioral, cognitive, and/or stein-Barr virus, 13 patients; cytomegalovirus, 11; rick- mood changes, 18 patients; encephalopathy, 9; cranial ettsial , 8; , 5, Whipple disease, 4; palsies, 4; Lambert-Eaton myasthenic syndrome and herpes simplex virus, 4; varicella zoster virus, 4; and hu- ataxia, 1; and disorder, 1. The 2 patients with man immunodeficiency virus (HIV), 3. All results were NMDA receptor antibody had initial symptoms of promi- negative. All 21 patients underwent evaluations for oc- nent behavioral and/or mood change followed by en- cult cancer, and carcinoma was documented in 3 (breast cephalopathy, with opsoclonus and myoclonus addition- adenocarcinoma, 2; and small cell lung carcinoma, 1) ally observed. The causes reported were paraneoplastic, (Table 1). Of the 3 patients with carcinoma, patients 7 60 patients (breast and lung cancers were the most com- and 10 had cancer discovered after onset of OMS and pa- mon; ANNA-2 was the most common paraneoplastic an- tient 2 had breast cancer diagnosis and treatment 4 years tibody detected); none identified, 38 (occurred during before the onset of OMS; oncologic evaluations under- pregnancy in 2 women); proven parainfectious, 15 (in- taken at the time of the development of OMS did not re- cluding 7 with HIV infection); other autoimmune, 1 veal cancer recurrence, and patient 2 had remained can- (GAD65 antibody seropositive); hyperosmolar nonke- cer free for 9 years at the final follow-up. totic diabetic , 1; and cocaine ingestion, 1. Outcome information was available for 115 patients Treatment and Outcomes (Table 3). For 41 patients, reported outcomes for a single treatment type (immunotherapy, oncologic therapy, Of 21 patients, some follow-up data were available for symptomatic therapy, or other therapy) could be inter- 19 (Table 2 and video; http://www.archneurol.com). Im- preted. Improvements were attributed to immuno- munotherapy was initiated in 18 of these patients (me- therapy alone in 22 of 28 patients treated; median dura- dian, 4 weeks after symptom onset; range, 1-54 weeks) tion of treatment was 6 weeks (range, 1-112 weeks). These and was continued for a median of 2 weeks (range, 1-112 treatments were corticosteroids, 8 patients; IVIG, 6; cor- weeks). Fifteen patients received combinations of im- ticosteroids and IVIG, 4; corticosteroids and plasma- munotherapy (corticosteroids and intravenous immu- pheresis, 1; and other combinations, 3. Improvements noglobulin [IVIG], 11; corticosteroids and plasmapher- were attributed to oncologic therapy in all 10 treated pa- esis, 2; and corticosteroids, IVIG, and plasmapheresis, tients (Ն1 of surgery, chemotherapy, and radio- 2), and 3 patients received corticosteroid (2) or IVIG (1) therapy); symptomatic therapy in 8 of 9 patients treated monotherapy. Because of an early relapse after discon- (benzodiazepines alone, 7; benzodiazepines with val- tinuing immunotherapy, patient 17 required long-term proic acid, 1); ceftriaxone sodium, 2 (both patients had (Ͼ2 years) therapy with mycophenolate mofetil during and improved); combination antiretro- and after treatment with corticosteroids and IVIG. Symp- viral therapy (neurologic symptoms in 1 HIV-positive pa- tomatic medications used in 17 patients (simultaneous tient resolved); and insulin, 1 (resolved on treatment of to immunotherapy in 16) were clonazepam (14 pa- diabetic coma). Fifty-three other patients received com- tients; median total daily dose, 3 mg; range, 1-6 mg), gab- binations of 1 or more of the treatment types listed. Of apentin (3 patients; median total daily dose, 900 mg; range, the 21 remaining patients who received no treatment, 18 900-1200 mg), valproic acid (2 patients; median total daily were reported to have spontaneous remission (15 pa- dose, 1125 mg; range, 1000-1250 mg), baclofen (1 pa- tients) or improvement (3). tient; total daily dose, 45 mg), and levetiracetam (1 pa- tient; total daily dose, 3000 mg). COMMENT Although outcomes were clearly documented, the ben- efits of individual treatments were usually difficult to as- sess because a combination of therapies was used simul- This study represents a large single-institution case se- taneously in all but 3 patients. Those 3 patients (2, 4, and ries of consecutively evaluated patients with adult- 10) who received monotherapy (immunotherapy, 2 pa- onset OMS. We observed that many patients had an id- tients; and clonazepam, 1) improved. Final outcomes were iopathic (presumed parainfectious) disorder of short remission, 13 patients; improvement, 3; and death, 3 duration, with full recovery after 4 to 6 weeks of treat- (caused by neurologic decline, 1; cancer, 1; and myocar- ment, usually immunotherapy and clonazepam com- dial infarction, 1). Patient 10 was symptomatic for 32 bined. Nonetheless, in the Mayo Clinic patients, cancer weeks before treatment and improved but required a was an important cause (14%), and a few patients also walker to ambulate and had residual dysarthria. had a relapsing course or a poor outcome. Findings from CSF analysis helped to confirm an autoimmune cause, but neural autoantibodies (including paraneoplastic an- LITERATURE REVIEW PATIENTS tibodies) were not detected in any of our patients de- spite comprehensive serologic evaluations. Paraneoplas- We identified 116 patients reported in 66 publica- tic autoantibody detection was similarly uncommon (2 tions5-8,17-78 (Table 3). The median age at symptom on- of 24 patients with opsoclonus or OMS) in a multi-

ARCH NEUROL / VOL 69 (NO. 12), DEC 2012 WWW.ARCHNEUROL.COM 1601

©2012 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 Table 2. Treatment and Outcome Data for 21 Adults With Opsoclonus-Myoclonus Syndrome

Symptom Duration Before Duration of Symptomatic Initial Total Patient Immunotherapy, Immunotherapy, Therapy for Outcome, Final Follow-up, No. Cause wk Immunotherapya wk Myoclonus Յ1mo Outcome mo 1 Unknown 1 PLEX, 3 times; 4 Clonazepam, Progressive Died 1 prednisone, unknown unknown dose neurologic dose decline, died 1 mo after symptom onset 2 Paraneoplastic No immunotherapy NA NA Clonazepam Only minimal Neurologic 145 opsoclonus remission 3 Unknown 2 IV methylprednisolone, 2 Clonazepam, Neurologic Neurologic 96 1 g, 5 doses; IVIG, 0.5 mg, remission, apart remission 5 doses 2 times/d from brief, infrequent attacks of opsoclonus 4 Unknown 4 IV methylprednisolone, 2 None Improvement Neurologic 59 1 g, 5 doses; IVIG, remission 5 doses 5 Unknown NA Unknown 0 Clonazepam Unknown Unknown None 6 Unknown 8 IV methylprednisolone, 2 Clonazepam, Neurologic Neurologic 187 1 g, 5 doses; IVIG, 1-2 mg, remission remission 5 doses; PLEX, 3 times/d 5 times 7 Paraneoplastic 4 IVIG, 3 doses; IV 2 Clonazepam Significant Died 13 methylprednisolone, improvement 1 g, 5 doses but still required gait assistance 8 Unknown 54 IV methylprednisolone, 1 Valproic acid, Occasional Neurologic 162 1 g, 5 doses 750 mg, myoclonus remission morning; 500 mg, evening 9 Unknown 12 IV methylprednisolone, Clonazepam Marked Death from 20 unknown duration or improvement, myocardial dose; PLEX, continued infarction 1 y 7 times improvement at after symptom final follow-up onset with neurologic symptoms at time of death 10 Paraneoplastic 32 IVIG, 3 doses/wk for 26 None Improved balance, Improved, but mild 27 3 wk; IVIG, 2 clearer speech dysarthria doses/wk for 2 wk; persisted; IVIG, 8 doses during required 3 mo; total, walker/scooter 21 doses for ambulation 11 Unknown 2 IV methylprednisolone, 2 Clonazepam (too Improvement Unknown 1.5 1 g, 5 doses; IVIG, sedated); 3 doses divalproex sodium, 500 mg, 2 times/d 12 Unknown 4 IV methylprednisolone, 2 Clonazepam, Symptoms Neurologic 107 1 g, 3 doses; IVIG, 1mg persisted, remission 5 doses 3 times/d; required gabapentin, inpatient 300 mg, rehabilitation 3 times/d 13 Unknown 2 Prednisone, unknown 3 Clonazepam, Improvement Neurologic 104 dose or duration; 1.5 mg, remission IVIG, 3 doses 3 times/d; gabapentin, 300 mg, 3 times/d 14 Unknown 2 IV methylprednisolone, 2 Clonazepam, Symptoms Neurologic 99 1 g, 3 doses; IVIG, 1 mg, resolved, except remission 7 doses 3 times/d opsoclonus

(continued)

institutional Spanish study.7 Our interpretation of indi- view of the literature. Several patients reported in the vidual treatments (immunotherapeutic vs sympto- literature7 had mild coexisting neurologic or neuropsy- matic) was limited because most patients received both chiatric symptoms, but outright encephalopathy was un- immunologic and symptomatic therapies simultane- common except in paraneoplastic cases. It was informa- ously. We expanded on our data with a systematic re- tive that both patients with NMDA receptor antibodies

ARCH NEUROL / VOL 69 (NO. 12), DEC 2012 WWW.ARCHNEUROL.COM 1602

©2012 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 Table 2. Treatment and Outcome Data for 21 Adults With Opsoclonus-Myoclonus Syndrome (continued)

Symptom Duration Before Duration of Symptomatic Initial Total Patient Immunotherapy, Immunotherapy, Therapy for Outcome, Final Follow-up, No. Cause wk Immunotherapya wk Myoclonus Յ1mo Outcome mo 15 Unknown 4 IV methylprednisolone, 3 Clonazepam, Symptoms Neurologic 43 125 mg, unknown 1 mg, resolved, except remission duration; IVIG, 3 times/d; opsoclonus 5 doses; PLEX, gabapentin, 7 times plus IV 400 mg, methylprednisolone, 3 times/d 1 g, on alternate days 16 Unknown 6 IV methylprednisolone, 8 Clonazepam, Improvement, but Mild symptoms 40 1 g, unknown 2 mg, relapse duration; IVIG, 2 times/d 9 doses 17 Unknown 2 IV methylprednisolone, 112 Clonazepam, Improvement, but Neurologic 36 1g,for5d;IVIGfor 0.5 mg, relapse remission 3 d; then weekly IVIG 3 times/d alternating with IV methylprednisolone, 1 g, for 6 wk; then IV methylprednisolone, 1 g, every other week for 4 wk; every 3 wk, 3 doses; monthly for 6 mo; every 6 wk, 4 doses; total IV methylprednisolone, 1 g, 25 doses; mycophenolate mofetil, 1500 mg, 2 times/d for 16 mo 18 Unknown 2 Unknown 1 Clonazepam, Unknown Unknown None 1 mg, 3 times/d 19 Unknown 3 IV methylprednisolone, 1 Clonazepam, Neurologic Unknown 1 1 g, 5 doses 1 mg, 4 remission times/d 20 Unknown 8 IVIG plus IV 16 Baclofen, 15 mg, Improvement Neurologic 7 methylprednisolone, 3 times/d remission 1 g, for 3 d; weekly for 6 wk; every other wk for 6 wk 21 Unknown 12 IVIG for 3 d; IVIG plus IV 12 Levetiracetam, Improvement Neurologic 14 methylprednisolone, 1500 mg, remission 1 g/wk for 6 wk; every 2 times/d other week for 6 wk

Abbreviations: IV, intravenous; IVIG, IV immune globulin; NA, not available; PLEX, plasma exchange. a When IV methylprednisolone was administered, methylprednisolone acetate was used.

had coexisting neuropsychiatric symptoms followed by number of patients with cancer. Bataller et al7 reported encephalopathy.8,71 that older age, higher frequency of encephalopathy, Among both the Mayo Clinic patients and those re- and a more severe clinical course are more common ported in the literature, lung and breast carcinomas were among paraneoplastic cases. Patients from our cohort the most common cancers identified, and ANNA-2 was were similar in age and sex profile as well as clinical the most commonly reported paraneoplastic antibody.* presentation to patients reported in the literature. In The diversity of reported paraneoplastic autoantibod- contrast, the proportion of patients in the collated lit- ies, including those with specificity for other neuronal erature with an established cause (62%) was much nuclear antigens,7,35 neuronal calcium channels,69,77 and 8,71 higher than in our series. Since individual reported NMDA receptors, serves to emphasize the impor- cases usually have rare or unique characteristics tance of comprehensive paraneoplastic serologic evalu- prompting description, this higher proportion of para- ations (rather than syndrome-specific physician- neoplastic cases in the literature compared with our selected antibody testing) in these patients. Rarer oncologic associations that merit exclusion include mela- clinical practice may represent a reporting bias. Other 41,53,55 34,37,40,42,55,70 myoclonic presentations that ought to be recognized noma and neoplasms of the gynecologic, 30 urologic,6,43 hematologic,51 and gastrointestinal systems.7 as possibly paraneoplastic include opsoclonus only, Comparison of paraneoplastic and idiopathic cases progressive encephalomyelitis with rigidity and myo- 79 was not possible within our own cohort given the low clonus, and isolated generalized small-amplitude limb and axial myoclonus.80 This latter group has *References 5-7, 36, 40, 45, 48, 50, 61, 62. myoclonus but no opsoclonus as an additional

ARCH NEUROL / VOL 69 (NO. 12), DEC 2012 WWW.ARCHNEUROL.COM 1603

©2012 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 Table 3. Literature Review Patients: Summary of Findings Among 116 Reported Patients With OMS

Paraneoplastic Cause (n = 60) Paraneoplastic Antibody Ն1 Coexisting With Presenting Myoclonus Neurologic Cancers Corresponding Infectious Other Symptom Distribution Disorder Detected Cancer Causes Causes Outcomes (n = 93) (n = 87) (n = 33) (n = 55) (n = 21)a (n = 15) (n=5) (n = 115) Dizziness, G, 44 Behavior Small cell lung ANNA-2, anti-Ri, HIV, 7; 2 of these Other Remission, 51; 44 changes, 18b carcinoma, 26 14; breast had TB autoimmune, 18 of these adenocar- , 1 1; GAD65 Ab, were cinoma, 4; had 1 spontaneous none found, 3; pulmonary non–small cell TB, 1 had EBV lung carcinoma, 3; small cell lung carcinoma, 2; ovarian, 1; bladder carcinoma, 1 Imbalance, AE, 15 Non–small cell Mild symptoms, 35 lung burgdorferi,2 33 carcinoma, 7 Nausea, 32 T only, 9 Encephalopathy, Breast NMDA-R Ab, 2; Streptococcal During Rapid 9 adenocar- none found, 2 throat pregnancy deterioration cinoma, 7 infection, 1 (presumed and death, 12 autoimmune), 2 Tremor, 20 CC, 4 Melanoma, 3 , 1 Improved but residual significant disability, 12 Vision CC and T, CN palsy, 4 Ovarian Calcium channel, CMV, 1 Hyperosmolar No improvement, disturbed, 4 carcinoma, 3 P/Q or N-type, nonketotic 7 15 2; small cell diabetic coma, lung 1 carcinoma, 2 Seizure HD, 4 Renal cell EBV, 1 Total deaths, 28; disorder, carcinoma, 2 cancer, 10; 3 neurologic disorder, 8; sepsis, 1; pulmonary embolism, 1; unknown/ not documented, 8 , 2 UE only, 3 SZ, 1 Medullary ANNA-1; anti-Hu, Coxsackie virus, Cocaine, 1 carcinoma 2; small cell 1 thyroid, 1 lung carcinoma, 2 Headache, 2 LE, 3 Ovarian West Nile virus, teratoma, 1 1 Hearing T and UE, LEMS and Esthesioneuro- Amphiphysin loss, 1 2 cerebellar blastoma, 1 IgG, 1; small degeneration, cell lung 1 carcinoma, 1 (same patient ANNA-1 seropositive) Anxiety, 1 T and LE, B-cell 2 lymphoma, 1 RUE, 1 Cervical carcinoma in situ, 1 Bladder carcinoma, 1 Gastric adenocar- cinoma, 1

Abbreviations: AE, all extremities; ANNA-2, antineuronal nuclear antibody type 2; CC, craniocervical; CMV, cytomegalovirus; CN, cranial nerve; EBV, Epstein-Barr virus; G, generalized; GAD65 Ab, glutamic acid decarboxylase 65 kDa isoform antibody; HD, hyperkinetic dysarthria; HIV, human immunodeficiency virus; LE, lower extremities; LEMS, Lambert-Eaton myasthenic syndrome and cerebellar degeneration; NMDA Ab, N-methyl-D-aspartate receptor antibody; OMS, opsoclonus-myoclonus syndrome; RUE, right upper extremity; SZ, seizure disorder; T, trunk; TB, tuberculosis; UE, upper extremities. a Of 76 patients tested, 20 were seropositive for at least 1 paraneoplastic antibody. b Coexisting neurologic disorders: changes in cognition, mood, personality, and behavior.

ARCH NEUROL / VOL 69 (NO. 12), DEC 2012 WWW.ARCHNEUROL.COM 1604

©2012 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 diagnostic clue; these patients report only tremulous- served for signs of relapse once therapy is completed, be- ness and therefore may receive a misdiagnosis of fore considering further treatment. The rare patient re- tremor, and frequently have a paraneoplastic disorder. quiring longer treatment may benefit from a corticosteroid/ Most patients in our cohort with an idiopathic diag- IVIG-sparing immunosuppressant, such as mycophenolate nosis were assumed to have a parainfectious autoim- mofetil or azathioprine. As illustrated by patient 10 (di- mune cause of OMS, based on the self-limited symp- agnosis and treatment after 32 weeks of symptoms and toms, CSF findings, absence of cancer or paraneoplastic only partial recovery) and by the pediatric literature,83,84 antibody, and response to immunotherapy; none had a early initiation of immunotherapy appears to be impor- specific cause identified. The findings from the litera- tant to ensure an optimal neurologic outcome. ture review reinforce the importance of thorough evalu- Symptomatic therapy was almost universally used ations for a parainfectious cause, including HIV.65,66,74 Op- among the Mayo Clinic cohort, usually as an adjunct to soclonus-myoclonus syndrome may develop during the immunotherapy, but may be effective as monotherapy HIV seroconversion illness66,74 or during immune recon- in mild cases of OMS.33,39,65,66,74 Effective reported thera- stitution after initiation of antiretroviral therapy.74 The pies include benzodiazepines,54 gabapentin,42,85 val- cause of OMS in HIV is probably autoimmune, since au- proic acid25,30,33,43,46,53,59,70 and levetiracetam.70,80 toimmunity is common in HIV-positive patients, and OMS is also responsive to corticosteroid therapy in this con- Accepted for Publication: April 4, 2012. text.65 For other infectious causes, successful treat- Published Online: September 17, 2012. doi:10.1001 ments have included corticosteroids and/or IVIG alone /archneurol.2012.1173 combined with antimicrobial therapy, when appropri- Correspondence: Andrew McKeon, MD, Department of ate.30,44,52,56,58,68,78 Other infectious causes reported in pa- Laboratory Medicine and Pathology, Hilton 3-78, Mayo tients with opsoclonus but without myoclonus include Clinic, 200 First St SW, Rochester, MN 55906 (mckeon psittacosis, salmonella, St Louis , and Rick- [email protected]). ettsia conorii.30 Author Contributions: Study concept and design: Klaas Rare nonparaneoplastic, nonparainfectious autoim- and McKeon. Acquisition of data: Klaas, Matsumoto, mune cases have been reported, including a patient with Aksamit, Kumar, McEvoy, and McKeon. Analysis and in- GAD65 antibody.59 Another unusual reported entity is terpretation of data: Klaas, Ahlskog, Pittock, Aksamit, OMS developing during pregnancy, which is assumed Bartleson, and McKeon. Drafting of the manuscript: Klaas (like chorea gravidarum81,82) to have an autoimmune cause and McKeon. Critical revision of the manuscript for im- and is similarly responsive to immunotherapy.49 portant intellectual content: Klaas, Ahlskog, Pittock, Mat- Most Mayo Clinic patients were very responsive to sumoto, Aksamit, Bartleson, Kumar, and McEvoy. Ad- treatment. Almost all patients received short-term ministrative, technical, and material support: Bartleson and immunotherapy in combination with symptomatic Kumar. Study supervision: Aksamit and McKeon. therapy and did not experience relapse on discontinu- Conflict of Interest Disclosures: None reported. ing therapy. Few required further immunotherapy for Online-Only Content: The video is available at http: longer periods to maintain remission. The literature //www.archneurol.com. review clarified the benefits of immunotherapy; we were able to determine that 79% of patients who received only immunotherapies achieved remission or REFERENCES improvement regardless of the cause of OMS. Cancer was identified in some of these patients, and cancer- 1. Kinsbourne M. Myoclonic encephalopathy of infants. J Neurol Neurosurg Psychiatry. 1962;25(3):271-276. specific treatments (surgery, chemotherapy, and radia- 2. Rudnick E, Khakoo Y, Antunes NL, et al. Opsoclonus-myoclonus-ataxia syn- tion) were effective either alone or in combination with drome in neuroblastoma: clinical outcome and antineuronal antibodies—a re- other therapies.† The benefits of chemotherapy prob- port from the Children’s Cancer Group Study. Med Pediatr Oncol. 2001;36 ably stem from the elimination of cancer but also the (6):612-622. immunosuppressant effects of those drugs. Although 3. Hayward K, Jeremy RJ, Jenkins S, et al. Long-term neurobehavioral outcomes in children with neuroblastoma and opsoclonus-myoclonus-ataxia syndrome: re- the prognosis with OMS is worse among paraneoplastic lationship to MRI findings and anti-neuronal antibodies. J Pediatr. 2001;139 7 cases than among idiopathic cases, long-term survival (4):552-559. is possible for some patients.63 4. Mitchell WG, Davalos-Gonzalez Y, Brumm VL, et al. Opsoclonus-ataxia caused It was somewhat informative to find that spontane- by childhood neuroblastoma: developmental and neurologic sequelae. Pediatrics. 2002;109(1):86-98. ous remissions may occur; however, because the conse- 5. Dropcho EJ, Kline LB, Riser J. Antineuronal (anti-Ri) antibodies in a patient with quences of OMS may be profound, we do not advocate a steroid-responsive opsoclonus-myoclonus. Neurology. 1993;43(1):207-211. wait-and-see approach. A practical treatment guide based 6. Pittock SJ, Lucchinetti CF, Lennon VA. Anti-neuronal nuclear autoantibody type on our experience and that of others could include an 2: paraneoplastic accompaniments. Ann Neurol. 2003;53(5):580-587. initial short course of either intravenous methylpred- 7. Bataller L, Graus F, Saiz A, Vilchez JJ; Spanish Opsoclonus-Myoclonus Study Group. Clinical outcome in adult onset idiopathic or paraneoplastic nisolone acetate or IVIG, administered daily for 3 to 5 opsoclonus-myoclonus. Brain. 2001;124(pt 2):437-443. days, followed by weekly treatments for 6 weeks. Com- 8. Smith JH, Dhamija R, Moseley BD, et al. N-methyl-D-aspartate receptor autoim- bination immunotherapy and plasma exchange could be mune encephalitis presenting with opsoclonus-myoclonus: treatment response reserved for patients whose condition is refractory to IVIG to plasmapheresis. Arch Neurol. 2011;68(8):1069-1072. 9. McKeon A, Tracy JA, Pittock SJ, Parisi JE, Klein CJ, Lennon VA. Purkinje cell or corticosteroid monotherapy. Patients could be ob- cytoplasmic autoantibody type 1 accompaniments: the cerebellum and beyond. Arch Neurol. 2011;68(10):1282-1289. †References 6, 7, 31, 32, 37, 42, 48, 50, 75, 77. 10. McKeon A, Lennon VA, Lachance DH, Fealey RD, Pittock SJ. Ganglionic acetyl-

ARCH NEUROL / VOL 69 (NO. 12), DEC 2012 WWW.ARCHNEUROL.COM 1605

©2012 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 choline receptor autoantibody: oncological, neurological, and serological soclonus-myoclonus-ataxia in ovarian duct cancer. J Neurol. 1998;245(10): accompaniments. Arch Neurol. 2009;66(6):735-741. 691-692. 11. Lennon VA, Kryzer TJ, Griesmann GE, et al. Calcium-channel antibodies in the 41. Berger JR, Mehari E. Paraneoplastic opsoclonus-myoclonus secondary to ma- Lambert-Eaton syndrome and other paraneoplastic syndromes. N Engl J Med. lignant melanoma. J Neurooncol. 1999;41(1):43-45. 1995;332(22):1467-1474. 42. Moretti R, Torre P, Antonello RM, Nasuelli D, Cazzato G. Opsoclonus- 12. Tan KM, Lennon VA, Klein CJ, Boeve BF, Pittock SJ. Clinical spectrum of voltage- myoclonus syndrome: gabapentin as a new therapeutic proposal. Eur J Neurol. gated potassium channel autoimmunity. Neurology. 2008;70(20):1883-1890. 2000;7(4):455-456. 13. Yu Z, Kryzer TJ, Griesmann GE, Kim K, Benarroch EE, Lennon VA. CRMP-5 neu- 43. De Luca S, Terrone C, Crivellaro S, et al. Opsoclonus-myoclonus syndrome as a ronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. paraneoplastic manifestation of renal cell carcinoma: a case report and review Ann Neurol. 2001;49(2):146-154. of the literature. Urol Int. 2002;68(3):206-208. 14. Graus F, Vincent A, Pozo-Rosich P, et al. Anti-glial nuclear antibody: marker of 44. Verma A, Brozman B. Opsoclonus-myoclonus syndrome following Epstein-Barr lung cancer-related paraneoplastic neurological syndromes. J Neuroimmunol. virus infection. Neurology. 2002;58(7):1131-1132. 2005;165(1-2):166-171. 45. Wirtz PW, Sillevis Smitt PA, Hoff JI, et al. Anti-Ri antibody positive opsoclonus- 15. Quek A, Britton JW, McKeon A, et al. Autoimmune : clinical character- myoclonus in a male patient with breast carcinoma. J Neurol. 2002;249(12): istics and response to immunotherapy. Arch Neurol. 2012;69(5):582-593. doi: 1710-1712. 10.1001/archneurol.2011.2985. 46. Glatz K, Meinck HM, Wildemann B. Parainfectious opsoclonus-myoclonus syn- 16. Pittock SJ, Yoshikawa H, Ahlskog JE, et al. Glutamic acid decarboxylase auto- drome: high dose intravenous immunoglobulins are effective. J Neurol Neuro- immunity with brainstem, extrapyramidal, and dysfunction. Mayo Clin surg Psychiatry. 2003;74(2):279-280. Proc. 2006;81(9):1207-1214. 47. Blaes F, Jauss M, Kraus J, et al. Adult paraneoplastic opsoclonus-myoclonus 17. Ross AT, Zeman W. Opsoclonus, occult carcinoma, and chemical pathology in syndrome associated with antimitochondrial autoantibodies. J Neurol Neuro- dentate nuclei. Arch Neurol. 1967;17(5):546-551. surg Psychiatry. 2003;74(11):1595-1596. 18. Cogan DG. Opsoclonus, body tremulousness, and benign encephalitis. Arch 48. Erlich R, Morrison C, Kim B, Gilbert MR, Alrajab S. ANNA-2: an antibody asso- Ophthalmol. 1968;79(5):545-551. ciated with paraneoplastic opsoclonus in a patient with large-cell carcinoma of 19. Baringer JR, Sweeney VP, Winkler GF. An acute syndrome of ocular oscillations the lung with neuroendocrine features—correlation of clinical improvement with and truncal myoclonus. Brain. 1968;91(3):473-480. tumor response. Cancer Invest. 2004;22(2):257-261. 20. McLean DR. Polymyoclonia with opsoclonus. Neurology. 1970;20(5):508-512. 49. Koide R, Sakamoto M, Tanaka K, Hayashi H. Opsoclonus-myoclonus syndrome 21. Brichet B, Andre´ JM, Reny A, Weber M. EMG study of opsoclonus occurring in during pregnancy. J Neuroophthalmol. 2004;24(3):273. vertebro-basilar insufficiency. Electroencephalogr Clin Neurophysiol. 1970; 50. Weizman DA, Leong WL. Anti-Ri antibody opsoclonus-myoclonus syndrome and 29(5):534. breast cancer: a case report and a review of the literature. J Surg Oncol. 2004; 22. Boddie HG. Ocular bobbing and opsoclonus: two abnormal spontaneous eye move- 87(3):143-145. ments occurring in the same patient: case report. J Neurol Neurosurg Psychiatry. 51. Kumar A, Lajara-Nanson WA, Neilson RW Jr. Paraneoplastic opsoclonus- 1972;35(5):739-742. myoclonus syndrome: initial presentation of non-Hodgkin’s lymphoma. 23. Vignaendra V, Lim CL. Electro-oculographic analysis of opsoclonus: its relation- J Neurooncol. 2005;73(1):43-45. ship to saccadic and nonsaccadic eye movements. Neurology. 1977;27(12): 52. Khosla JS, Edelman MJ, Kennedy N, Reich SG. West Nile virus presenting as 1129-1133. opsoclonus-myoclonus cerebellar ataxia. Neurology. 2005;64(6):1095. 24. Jabbari B, Urban E. Abnormal visual-evoked responses and opsoclonus. J Clin 53. Jung KY, Youn J, Chung CS. Opsoclonus-myoclonus syndrome in an adult with Neuroophthalmol. 1981;1(4):269-271. malignant melanoma. J Neurol. 2006;253(7):942-943. 25. Sheinman BD, Gawler J. Opsoclonus and polymyoclonia complicating oat-cell 54. Bartos A. Effective high-dose clonazepam treatment in two patients with opsoc- carcinoma of the bronchus. Postgrad Med J. 1982;58(685):704-705. lonus and myoclonus: GABAergic hypothesis. Eur Neurol. 2006;56(4):240- 26. Graus F, Cordon-Cardo C, Cho ES, Posner JB. Opsoclonus and oat cell carci- 242. noma of lung: lack of evidence for anti-CNS antibodies. Lancet. 1984;1(8392): 55. Hauspy J, Nevin A, Harley I, et al. in vaginal mela- 1479. noma: a case report and review of the literature. Int J Gynecol Cancer. 2007; 27. Sachdeva JR Jr, Singh N, Mann GS. Acute cerebellar ataxia with opsoclonus. 17(5):1159-1163. J Assoc Physicians India. 1984;32(5):460. 56. Zaganas I, Prinianakis G, Xirouchaki N, Mavridis M. Opsoclonus-myoclonus syn- 28. Rosenberg NL. Hearing loss as an initial symptom of the opsoclonus- drome associated with cytomegalovirus encephalitis. Neurology. 2007;68(19): myoclonus syndrome. Arch Neurol. 1984;41(9):998-999. 1636. 29. Matsumura K, Sonoh M, Tamaoka A, Sakuta M. Syndrome of opsoclonus- 57. Ohara S, Iijima N, Hayashida K, Oide T, Katai S. Autopsy case of opsoclonus- myoclonus in hyperosmolar nonketotic coma. Ann Neurol. 1985;18(5):623- myoclonus-ataxia and cerebellar cognitive affective syndrome associated with 624. small cell carcinoma of the lung. Mov Disord. 2007;22(9):1320-1324. 30. Digre KB. Opsoclonus in adults: report of three cases and review of the literature. 58. Skeie GO, Eldøen G, Skeie BS, Midgard R, Kristoffersen EK, Bindoff LA. Opso- Arch Neurol. 1986;43(11):1165-1175. clonus myoclonus syndrome in two cases with neuroborreliosis. Eur J Neurol. 31. Dropcho E, Payne R. Paraneoplastic opsoclonus-myoclonus: association with 2007;14(12):e1-e2. doi:10.1111/j.1468-1331.2007.01959.x. medullary thyroid carcinoma and review of the literature. Arch Neurol. 1986; 59. Markakis I, Alexiou E, Xifaras M, Gekas G, Rombos A. Opsoclonus-myoclonus- 43(4):410-415. ataxia syndrome with autoantibodies to glutamic acid decarboxylase. Clin Neu- 32. Anderson NE, Budde-Steffen C, Rosenblum MK, et al. Opsoclonus, myoclonus, rol Neurosurg. 2008;110(6):619-621. ataxia, and encephalopathy in adults with cancer: a distinct paraneoplastic 60. Van Diest D, De Raeve H, Claes J, Parizel PM, De Ridder D, Cras P. Paraneo- syndrome. Medicine (Baltimore). 1988;67(2):100-109. plastic opsoclonus-myoclonus-ataxia (OMA) syndrome in an adult patient with 33. Scharf D. Opsoclonus-myoclonus following the intranasal usage of cocaine. J Neu- esthesioneuroblastoma. J Neurol. 2008;255(4):594-596. rol Neurosurg Psychiatry. 1989;52(12):1447-1448. 61. Brieva-Ru´ız L, Diaz-Hurtado M, Matias-Guiu X, Ma´rquez-Medina D, Tarragona 34. Scholz J, Vieregge P, Ruff C. Paraneoplastic opsoclonus-myoclonus syndrome J, Graus F. Anti-Ri-associated paraneoplastic cerebellar degeneration and breast in metastatic ovarian carcinoma. J Neurol Neurosurg Psychiatry. 1994;57(6): cancer: an autopsy case study. Clin Neurol Neurosurg. 2008;110(10):1044- 763-764. 1046. 35. Hersh B, Dalmau J, Dangond F, Gultekin S, Geller E, Wen PY. Paraneoplastic op- 62. Musunuru K, Kesari S. Paraneoplastic opsoclonus-myoclonus ataxia associ- soclonus-myoclonus associated with anti-Hu antibody. Neurology. 1994;44 ated with non–small-cell lung carcinoma. J Neurooncol. 2008;90(2):213-216. (9):1754-1755. 63. Hassan KA, Kalemkerian GP, Trobe JD. Long-term survival in paraneoplastic op- 36. Casado JL, Gil-Peralta A, Graus F, Arenas C, Lopez JM, Alberca R. Anti-Ri anti- soclonus-myoclonus syndrome associated with small cell lung cancer. bodies associated with opsoclonus and progressive encephalomyelitis with rigidity. J Neuroophthalmol. 2008;28(1):27-30. Neurology. 1994;44(8):1521-1522. 64. de Beer F, Schreurs MW, Foncke EM. False positive autoantibodies to glutamic 37. Caviness JN, Forsyth PA, Layton DD, McPhee TJ. The of adult acid decarboxylase in opsoclonus-myoclonus-ataxia syndrome after intrave- opsoclonus. Mov Disord. 1995;10(1):22-27. nous treatment with immunoglobulin. Clin Neurol Neurosurg. 2009;111(7): 38. Pless M, Ronthal M. Treatment of opsoclonus-myoclonus with high-dose intra- 643-644. venous immunoglobulin. Neurology. 1996;46(2):583-584. 65. Scott KM, Parker F, Heckmann JM. Opsoclonus-myoclonus syndrome and 39. Gwinn KA, Caviness JN. Electrophysiological observations in idiopathic opsoclonus- HIV-infection. J Neurol Sci. 2009;284(1-2):192-195. myoclonus syndrome. Mov Disord. 1997;12(3):438-442. 66. Ayarza A, Parisi V, Altclas J, et al. Opsoclonus-myoclonus-ataxia syndrome and 40. Jongen JL, Moll WJ, Sillevis Smitt PA, Vecht CJ, Tijssen CC. Anti-Ri positive op- HIV seroconversion. J Neurol. 2009;256(6):1024-1025.

ARCH NEUROL / VOL 69 (NO. 12), DEC 2012 WWW.ARCHNEUROL.COM 1606

©2012 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 67. Vandervest KM, Schwarz MI. A 76-year-old woman with acute CNS symptoms soclonus-myoclonus syndrome as a new and single manifestation of relapsing and pulmonary nodules. Chest. 2009;136(6):1686-1689. disease in a patient with small cell lung cancer. J Thorac Oncol. 2011;6(5): 68. Flabeau O, Meissner W, Foubert-Samier A, Guehl D, Desbordes P, Tison F. 968-969. Opsoclonus myoclonus syndrome in the context of salmonellosis. Mov Disord. 77. Simister RJ, Ng K, Lang B, Beckles M, Chao D, McCabe DJ. Sequential fluctu- 2009;24(15):2306-2308. ating paraneoplastic ocular flutter-opsoclonus-myoclonus syndrome and Lambert- 69. Josephson CB, Grant I, Benstead T. Opsoclonus-myoclonus with multiple para- Eaton myasthenic syndrome in small-cell lung cancer. J Neurol Neurosurg neoplastic syndromes and VGCC antibodies. Can J Neurol Sci. 2009;36(4): Psychiatry. 2011;82(3):344-346. 512-514. 78. Dassan P, Clarke C, Sharp DJ. A case of poststreptococcal opsoclonus- 70. Lou E, Hensley ML, Lassman AB, Aghajanian C. Paraneoplastic opsoclonus- myoclonus syndrome. Mov Disord. 2007;22(10):1490-1491. myoclonus syndrome secondary to immature ovarian teratoma. Gynecol Oncol. 79. Whiteley AM, Swash M, Urich H. Progressive encephalomyelitis with rigidity. Brain. 2010;117(2):382-384. 1976;99(1):27-42. 71. Kurian M, Lalive PH, Dalmau JO, Horvath J. Opsoclonus-myoclonus syndrome 80. McKeon A, Pittock SJ, Glass GA, et al. Whole-body tremulousness: isolated gen- in anti-N-methyl-D-aspartate receptor encephalitis. Arch Neurol. 2010;67(1): eralized polymyoclonus. Arch Neurol. 2007;64(9):1318-1322. 118-121. 81. Cardoso F. Chorea gravidarum. Arch Neurol. 2002;59(5):868-870. 72. Bier SA, Hile DC. Emergency department presentation of a rare neurological disorder. J Emerg Med. 2010;38(4):452-455. 82. Kranick SM, Mowry EM, Colcher A, Horn S, Golbe LI. Movement disorders and 73. Korn-Lubetzki I, Steiner-Birmanns B, Jaworowski S. Anxiety as initial diagnosis pregnancy: a review of the literature. Mov Disord. 2010;25(6):665-671. in opsoclonus myoclonus syndrome. Arch Neurol. 2010;67(9):1154-1155. 83. Pranzatelli MR, Tate ED, Travelstead AL, et al. Insights on chronic-relapsing op- 74. Kanjanasut N, Phanthumchinda K, Bhidayasiri R. HIV-related opsoclonus- soclonus-myoclonus from a pilot study of mycophenolate mofetil. J Child Neurol. myoclonus-ataxia syndrome: report on two cases. Clin Neurol Neurosurg. 2010; 2009;24(3):316-322. 112(7):572-574. 84. Pranzatelli MR. The immunopharmacology of the opsoclonus-myoclonus 75. Sotirchos ES, Dorsey ER, Tan IL, Zee DS. Opsoclonus-myoclonus syndrome and syndrome. Clin Neuropharmacol. 1996;19(1):1-47. exaggerated startle response associated with small-cell lung cancer. Mov Disord. 85. Pistoia F, Sarà M. Gabapentin therapy for ocular opsoclonus-myoclonus re- 2011;26(9):1769-1770. stores communication in a patient with a locked-in syndrome. 76. Nadal E, Bruna J, Ochoa de Olza M, Antonio M, Cardenal F. Paraneoplastic op- Neurorehabil Neural Repair. 2010;24(5):493-494.

ARCH NEUROL / VOL 69 (NO. 12), DEC 2012 WWW.ARCHNEUROL.COM 1607

©2012 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021