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Table e-1 . Clinical features of previous reported cases of thymoma-associated paraneoplastic encephalitis.
Patients Author Sex, age in years
Presentation and main
symptoms
History of autoimmunity
MRI CSF EEG Anti-Neuronal
Abs
Treatment Outcomes
1 Mcardle (1988)(1)
M, 41 Confusion, memory deficits
ANA (serum) Not available oligoclonal IgG bands
Not Available
No Partial, thymectomy, radiation, corticosteroids
Death (1 month)
2 Ingenito (1990)(2)
M, 59 Confusion, memory deficit, hyper somnolence, axial cerebellar ataxia
No Not reported 13 WBC Slow activity with frontal intermittent rhythmic delta activity
No Corticosteroids Death (51 days after admission, symptoms onset were 7 months before admission
3 Cunningham (1994)(3)
F, 56 Confusion, memory deficit, emotional lability
No Left temporallobe corticaland subcorti-cal lesionsnoted onT2 (no figures available)
Elevated protein level
Not reported
No(Negative anti-Hu)
Thymectomy, radiation, chemotherapy (three cycles of cisplatinandetoposide)
Significant improvement
4 Antoine (1995)(4)
F, 58 Confusion, visual and auditory hallucinations, short term memory loss
No Before treatment: increased signals on T2 weighted sequences in right hippocampusAfter treatment
36 lymphocytes/m3
Protein 0,3 g/l
Epileptic discharges in the right temporal lobe
Anti-neuronal Cytoplasmatic (serum 1/1500 and CSF 1/100)
Thymectomy and radiation
No residual symptoms
–normal(No figures available)
5 Antoine (1995)(4)
F, 67 Confusion, agitation, hallucination, short memory loss
Anti-striated muscle antibody (1/10)
Before treatment: mild increased signals in the right hippocampus on T2 weighted sequences
Normal after treatment (no figures available)
Normal Epileptic discharges in the left temporal lobe
Anti-neuronal Nuclear (serum and CSF)
ThymectomyRadiotherapy
Mild memory deficits (necessity of noting her shopping requirements)
6 Evoli (1999)(5,6)
M,32 New onset generalized tonic-clonic seizures and confusion, memory deficits
Myasthenia GravisNeuromyotonia
Before treatment: increased signal and swelling of both hippocampi on T2-weighted images
25 cells/mm3Normal protein and glucose
Theta background activity with sharp waves on both temporal lobes
No(negative anti-Hu)
Thymectomy, radiation, chemotherapy (cyclophosphamide, doxorubicin, vincristine and metilprednisolone), corticosteroids, PLEX
Mild memory deficits, (“good condition and has returned to work”)Dependent on corticosteroids
7 Rickman (2000)(7)
M,55 Malaise, fever, cough, dysarthria, intermittent twitching of right hand. One week after short-term memory, word finding difficulty.
AchR andStriational antibodies
MRI1: Patchy T2 hyperintensity in the gray matter of both cerebral hemisphere with no gadolinium enhancementMRI 2 (D35):
CSF 1: protein 69 mg/dLCSF 2: protein 63 mg/dl
Multifocal, independent, periodic, lateralizing epileptiform discharges (PLEDs)Fig 2)
Anti-CRMP-5 Partial thymectomy, pulse therapy (methylpredinisolone), PLEX
Initial responseRecurrence of symptomsDied (9 months)
Nystagmus, vertical gaze impairment, jerking movements of face, neck and arms, and left lower extremity. Intractable seizures
multiples areas of cortical signal abnormalities most prominent in the temporal lobes and spare subcortical and posterior fossa structuresMRI 3 (D105): cortical atrophy and reduced number of lesions, temporal lobe are still prominent
8 D’Avino (2001)(8)
M, 61 Short term memory loss, confusion, irritability, hallucinations, feeding disorders, loss of weight, generalized tonic clonic seizures (not described if it was refractoryMMSE: 23/30
No Normal(No available figures)
Positive OB
Theta backaground activity with sharp waves in both fronto-temporal lobes
Antibody reactivity to Purkinje cells (serum and CSF)
Thymectomy, radiation
Mild memory deficitsMMSE: 29
9 Fujii (2001)(9) M,55 Confusion, memory deficit, irritability, mania,3 generalized
Myastenia Gravis 15-years previoulsyAChR
Bilateral highIntensity (no available figures)
Normal No epileptic discharges
Hippocampus showing human IgG at autopsy
Thymectomy Death (4months)
tonic clonic seizures
antibodies
10 Vernino (2002)(10)
F, 66 Hoarseness, unilateral loss of hearing, vertigo, arreflexia
No Not reported Not reported
Not reported
ANNA-1 (anti-Hu), VGCC (serum)
Partial thymectomy, chemotherapy (two cycles of cisplatinandetoposide
Death (7 months)
11 Vernino (2002)(10)
M, 34 Presented with dysphagia and dysarthria being diagnosed as myasthenia gravis. After 1 month presented with confusion, auditory hallucination, and tonic clonic seizures
Myastenia GravisAChR antibodies
Normal (no available figures)
10 WBC with normal protein concentration
Diffuse slowing over the left temporal lobe
ANNA-1 (anti-Hu),
PLEX, thymectomy, corticosteroids
“Three months later, he was noted to be intermittently withdrawn and confused; no seizures were observed”
12 Vernino (2002)(10)
F, 34 Recurrent vertigo, tinnitus, and vomitingClonic activity of the tongue and jaw (seizures?)
Dysautonomia MRI 1: normalMRI 2:Non-enhancing left temporal lesionMRI 3 (11 days after):Four new enhancing cortical lesions (figure 1)
Elevated protein 78 mg/dL
Not reported
ANNA-1, VGKC
Thymectomy Residual symptoms, constipation, fixed right pupil
13 Vernino (2002)(10)
F, 39 Dysphagia, generalized
Myasthenia Gravis
Normal (no available
Not reported
Not reported
ANNA-1, CRMP-5,
Partial Thymectomy,
Not reported
weakness (attributed to Myasthenia Gravis)Personality changes
AChR andStriational antibodies
figures) radiation, chemotherapy (etoposide, cysplatin), corticosteroid, PLEX
14 a Ances (2005) – patient 5(11) corresponds to Lai (2009) patient 2(12)
F, 44 Hippocampal syndrome; pure short-term memory loss. Evolved to extensive LE, focal motor seizures
Not reported MRI(1) : normalMRI (2, after 5 days): mild temporal lobe FLAIR abnormalities (right>left), no contraste enhancement
0 WBC, protein 63 mg/dL, glucose 64 mg/dL
Not reported
Neuropil antibodies Later prove to be AMPAR Abs (12)
Thymectomy, corticosteroids, IVIg
Returned to baseline
15 Ances (2005) – patient 6(11) corresponds to Lai (2009) - patient 3(12)
M,38 Confusion, agitation, short-term memory loss, generalized tonic-clonic seizures (prior episode of Limbic Encephalitis 5 years earlier). Evolved to hippocampal and multifocal encephalitis, and stiff person syndrome
Stiff person FLAIR abnormalities in right medial and lateral temporal lobe, right frontal, left insular and left occipital regions. No contrast enhancement.
7 WBC, protein 50 mg/dL, glucose 92 mg/dL, positive OB. Positive ISAb, IgG index not examined
Not reported
Neuropil antibodies Later prove to be AMPAR Abs (12)
Thymectomy, corticosteroids, plasmapheresis, IVIg
Mild residual memory deficits and steroid-dependent muscle spasms and rigidity
16 Ohshita (2006)(13,14)
F, 59 3 years earlier years, invasive thymoma had been diagnosed
Positive single-stranded DNA antibodies
T2/FLAIR images demonstrated bilateral
Mild elevation of the protein
Normal VGKC (LGI1) andAnti-GABAaR(14)
Chemotherapy (carboplatin and etoposide)
Mental state partially improved
and treated with thymectomy and radiotherapySubacute onset of amnesia (short-term memory impairment), disorientation, and; 10 months later, progressive memory impairment and recurrence of thymoma
hyperintense areas in the medial part of the temporal lobe. High intensity lesions were also seen in the right insular cortex, as well as bilaterally in the frontobasal cortex and cingulate gyrus
content (60 mg/dl)
17 Chaudhry (2007)(15)
F, 67 Memory deficits, cognitive impairment. MMSE: 23
No Bilateral increased signal on FLAIR in both hippocampi. More extensive similar changes were on the left side extending to trigone and up to the level of the corpus callosum.
Protein: 67 mg/ 100 ml Positive OB
Not reported
Negative for anti-Hu, anti-Ri, anti-Yo and VKGC
Thymectomy, chemotherapy (cyclophosphamide, doxorubicin, cisplatin), rituximabe, PLEX
Progressive cognitive deficits
18 Khella (2007)(16)
F, 41 Headache, diplopia, nausea, dizziness. After
Myasthenia GravisAchR antibodies
Bright signal on T2 weighted and FLAIR in the right globus
43 WBC (66% of lymphocytes)
Not reported
Unknown antigen.in Serum and CSF,
Prednisone 1mg per kg for 90 days, IVIg (350 g), PLEX
Initial partial responseDeath with 31 days
9 weeks: recent memory loss, neck weakness on flexion and extension, horizontal and down beating.14 weeks from symptoms onset: sudden worsening of true vertigo and dysphagia, hyper somnolence and gait ataxia
palidus and substantia nigra and both thalami (no available figure)
Negative OB
Probably not exposed on cell surface
and cyclophosphamide
19 Gesundheit (2008)(17)
M, 28 Hallucinations, incoherent speech,“bizarre” disorganized movements of the limbs
No Showed subtle mesial temporal hyperintensity on FLAIR
Not reported
Unremarkable
Not reported Thymectomy
IVIg
No residual symptoms
20 Graus (2008) - patient 4 (18) correspond to Lai (2009) - patient 5 (12)
F, 41 Behavior change, confusion
Not reported Not performed (diagnosis if limbic encephalitis performed on autopsy)
15 WBC Not reported
CRMP-5 (CV-2) and NSA antibodies, later proved to be AMPAR Abs (12)
No Death (2 weeks)
21 Monstad (2009)(19)
F,49 Progressive loss of memory for recent events
MGAchR antibodies
Bilateral hippocampal lesions on
10 WBCNegative OB
Epileptic discharges in both
CRMP5 Thymectomy, PLEX
Short memory deficits
FLAIR(after treatment)
temporal lobes
22 Hammound (2009)(20)
F, 43 Seizures (not refractory), confusion and rapidly progressive mutism
MGAchR antibodies
Numerous cortically based signal abnormalities on FLAIR as well as extensive left mesial temporal lobe abnormality with minimal enhancement
70 WBCprotein: 101 mg/dL with normal glucose level
Intermittent periodic lateralized epileptiform discharges in the left temporal region
VGKC Thymectomy, radiation, chemotherapy, corticosteroids, IVIg
Death (2 months)
23 Rizzardi (2009)(21)
F, 55 Seizure and aphasia
No T2/FLAIR multiple lesions located in insular, parietal and
temporal lobes (in cortical and sub-cortical area) including limbic and extra limbic system
Normal Focal epileptic discharges in temporal-parietal left region
No Thymectomy, Radiation
No residual symptoms and disease free
24 Werry (2009)(22)
M, 32 Vertigo, diplopia and nystagmus, clumsiness of the left hand, olfactory disturbances, progressive gait ataxia, myoclonic
MG developed after encephalitis
MRI1: normal
MRI 2(4 weeks later): spots of cortical hyperintensity of the insula bilaterally, the medial right
CSF (1): 4 WBCProtein 58 mg/dL Negative OBCSF (2): 25WBC
Showed epileptic changes
CRMP-5 Corticosteroids, Thymectomy, PLEX, IVIg
Almost complete recovery except for complaints of headache, fatigue. After on year developed diplopia and ptosis and was diagnosed as MG
jerking temporal lobe and in the left parieto-occipital region on T2-weighted images. No contrast enhancement.
Protein: 65 mg/dL
25 Erkmen (2010)(23)
M, 61 Seizure, memory loss
No Bilateral foci of cortical and subcortical non-enhancing signal abnormalities on T2 weighted images
Lymphocytic pleocytosis
Not reported
LGI1 Thymectomy, radiation, methylprednisolone, IVIg
No residual symptoms and disease free
26 Miyasaki (2012)(14,24)
M, 46 Subacute onset of aphasia, visual hallucination,and generalized seizures with delirium; residual thymoma
MGAchR antibodies
Axial T2-weighted brain MR image showing multifocal signal abnormality
Protein: 60 mg/dL
Electroencephalogram showed diffuse slow wave back- ground and theta (h) waves with epileptic discharges dominant in the left temporal lobe
VGKC (LGI1)Anti-GABAaR (14)
Corticosteroids and IVIg; AED
Epileptic seizures disappeared; severe cognitive impairment and psychological symptoms remained
27 Shaulov F, 66 Short term MG Multiple T2 Normal Normal Negative Thymectomy, No residual symptoms
(2012)(25) memory loss, grand mal seizure
AchR antibodies
weighted high signal hiperintensities in the hippocampi bilaterally, with no enhancement with gadolinium
anti-HU AED developed MG 18 years after encephalitis.
28 Aysal (2013)(26)
M, 43 3 secondarily generalized tonic-clonic seizureRefractory complex partial seizures
MGAchR antibodies
Hyper intense lesions on T2/FLAIR on the left temporo-parietal, left insular, left frontal subcortical white matter, and the right hippocampus without contrast enhancement
Normal Background activity was disorganized (7-9 Hz)
Negative for VGKC
IVIg, thymectomy, DAE
No residual symptoms
29 Suh (2013)(27) F, 42 Short-term memory loss, personality changes and severe agitation
MGAchR antibodies
Multifocal high intensity signals in the cerebral cortex including the limbic area on T2 flare images
Not reported
Diffuse delta background activity and moderate diffuse cerebral dysfunction
Negative for anti-Hu, anti-Ri and anti-Yo
Thymectomy, radiotherapy
No residual symptoms
30 Alexopoulos (2014)(28)
M, 25 Recurrent episodes of vertigo,
Normal 10 WBC, protein
Normal Hu, CV2, GABAb
Thymectomy, oral prednisolone,
Slight dizziness and vertigo in the supine position
dizziness, hiccups, nausea, and vomiting, tongue myoclonus
85, normal glucosePositive OB
PLEX, corticosteroids, azathioprine
FootnotesAchR antibodies to acetylcholine receptors; AED, anti-epileptic drugs; ANNA-1, type-1 anti-neuronal nuclear antibody; anti-neuronal Ab, anti-neuronal antibodies; AMPAR Abs , α -amino- 3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antibodies; ANA, antinuclear antibody; CRMP5, collapsin response mediator; CSF, cerebrospinal fluid; EEG, electroencephalogram; FLAIR, fluid attenuated inversion recovery; GAD, glutamic acid decarboxylase;ISAb, intrathecal synthesis of antibodies, IVIg, intravenous immunoglobulin G; LGI1, Leucine-rich Glioma Inactivated 1; MMSE, Mini-Mental State Examination; MRI, magnetic ressonance imaging; NSA, novel surface antigens; OB, oligoclonal bands; PLEX, plasma exchange; VGKC, Voltage-gated potassium channel antibody; WBC, white blood cell count;
a This patient had thymic carcinoma
eTable References:
1. McArdle JP, Millingen KS. Limbic encephalitis associated with malignant
thymoma. Pathology (Phila). 1988 Jul;20(3):292–295.
2. Ingenito GG, Berger JR, David NJ, Norenberg MD. Limbic encephalitis
associated with thymoma. Neurology. 1990 Feb;40(2):382.
3. Cunningham JD, Burt ME. Limbic encephalitis secondary to malignant
thymoma. Ann Thorac Surg. 1994 Jul;58(1):250–251.
4. Antoine JC, Honnorat J, Anterion CT, Aguera M, Absi L, Fournel P, et al.
Limbic encephalitis and immunological perturbations in two patients with
thymoma. J Neurol Neurosurg Psychiatry. 1995 Jun;58(6):706–710.
5. Evoli A, Lo Monaco M, Marra R, Lino MM, Batocchi AP, Tonali PA. Multiple
paraneoplastic diseases associated with thymoma. Neuromuscul Disord
NMD. 1999 Dec;9(8):601–603.
6. Evoli A, Minicuci GM, Vitaliani R, Battaglia A, Marca GD, Lauriola L, et al.
Paraneoplastic diseases associated with thymoma. J Neurol. 2007 Jun
1;254(6):756–762.
7. Rickman OB, Parisi JE, Yu Z, Lennon VA, Vernino S. Fulminant
autoimmune cortical encephalitis associated with thymoma treated with
plasma exchange. Mayo Clin Proc. 2000 Dec;75(12):1321–1326.
8. D’Avino C, Lucchi M, Ceravolo R, Mussi A, Malandrini A, Annunziata P, et
al. Limbic encephalitis associated with thymic cancer: a case report. J
Neurol. 2001 Nov;248(11):1000–1002.
9. Fujii N, Furuta A, Yamaguchi H, Nakanishi K, Iwaki T. Limbic encephalitis
associated with recurrent thymoma: a postmortem study. Neurology. 2001
Jul 24;57(2):344–347.
10. Vernino S, Eggenberger ER, Rogers LR, Lennon VA. Paraneoplastic
neurological autoimmunity associated with ANNA-1 autoantibody and
thymoma. Neurology. 2002 Sep 24;59(6):929–932.
11. Ances BM, Vitaliani R, Taylor RA, Liebeskind DS, Voloschin A, Houghton
DJ, et al. Treatment-responsive limbic encephalitis identified by neuropil
antibodies: MRI and PET correlates. Brain J Neurol. 2005 Aug;128(Pt
8):1764–1777.
12. Lai M, Hughes EG, Peng X, Zhou L, Gleichman AJ, Shu H, et al. AMPA
receptor antibodies in limbic encephalitis alter synaptic receptor location.
Ann Neurol. 2009 Apr;65(4):424–434.
13. Ohshita T, Kawakami H, Maruyama H, Kohriyama T, Arimura K,
Matsumoto M. Voltage-gated potassium channel antibodies associated
limbic encephalitis in a patient with invasive thymoma. J Neurol Sci. 2006
Dec 1;250(1–2):167–169.
14. Ohkawa T, Satake S, Yokoi N, Miyazaki Y, Ohshita T, Sobue G, et al.
Identification and Characterization of GABAA Receptor Autoantibodies in
Autoimmune Encephalitis. J Neurosci. 2014 Jun 11;34(24):8151–8163.
15. Chaudhry MS, Waters M, Gilligan D. Paraneoplastic limbic encephalitis
attributable to thymoma. J Thorac Oncol Off Publ Int Assoc Study Lung
Cancer. 2007 Sep;2(9):879–880.
16. Khella SL, Souyah N, Dalmau J. Thymoma, myasthenia gravis,
encephalitis, and a novel anticytoplasmic neuronal antibody. Neurology.
2007 Sep 18;69(12):1302–1303.
17. Gesundheit B, Lerer B, Budowski E, Neuman T, Gomori JM, Or R. Sudden
psychotic symptoms in a 28-year-old male with thymoma. J Clin Oncol Off
J Am Soc Clin Oncol. 2008 Sep 10;26(26):4353–5.
18. Graus F, Saiz A, Lai M, Bruna J, López F, Sabater L, et al. Neuronal
surface antigen antibodies in limbic encephalitis: clinical-immunologic
associations. Neurology. 2008 Sep 16;71(12):930–936.
19. Monstad SE, Nøstbakken JK, Vedeler CA. CRMP5 antibodies found in a
patient with limbic encephalitis and myasthenia gravis. J Neurol Neurosurg
Psychiatry. 2009 Feb;80(2):241–242.
20. Hammoud K, Kandimala G, Warnack W, Vernino S. Multifocal
paraneoplastic cortical encephalitis associated with myasthenia gravis and
thymoma. Arch Neurol. 2009 Nov;66(11):1407–1409.
21. Rizzardi G, Campione A, Scanagatta P, Terzi A. Paraneoplastic extra
limbic encephalitis associated with thymoma. Interact Cardiovasc Thorac
Surg. 2009 Oct;9(4):755–756.
22. Werry C, Götz F, Wurster U, Stangel M, Giess R, Heidenreich F, et al.
Paraneoplastic autoimmune encephalitis associated with CV2/CRMP-5 IgG
antineuronal antibodies in a patient with thymoma. J Neurol. 2009
Jan;256(1):129–131.
23. Erkmen CP, Fadul CE, Dalmau J, Erkmen K. Thymoma-associated
paraneoplastic encephalitis (TAPE): diagnosis and treatment of a
potentially fatal condition. J Thorac Cardiovasc Surg. 2011
Feb;141(2):e17–20.
24. Miyazaki Y, Hirayama M, Watanabe H, Usami N, Yokoi K, Watanabe O, et
al. Paraneoplastic encephalitis associated with myasthenia gravis and
malignant thymoma. J Clin Neurosci Off J Neurosurg Soc Australas. 2012
Feb;19(2):336–338.
25. Shaulov A, Rottenstreich M, Peleg H, Spiegel M, Shichman B, Argov Z.
Myasthenia gravis appearing 18 years after resection of benign thymoma
with subsequent limbic encephalitis. J Neurol Sci. 2012 Jun 15;317(1-
2):146–147.
26. Aysal F, Baybas S, Selçuk HH, Sozmen V, Ozturk M, Kucukoglu H, et al.
Paraneoplastic extralimbic encephalitis associated with thymoma and
myastenia gravis: three years follow up. Clin Neurol Neurosurg. 2013
May;115(5):628–631.
27. Suh JW, Haam SJ, Song SW, Shin YR, Paik HC, Lee DY. Paraneoplastic
encephalitis associated with thymoma: a case report. Korean J Thorac
Cardiovasc Surg. 2013 Jun;46(3):234–236.
28. Alexopoulos H, Dagklis IE, Akrivou S, Bostantjopoulou S, Dalakas MC.
Autoimmune encephalitis with GABAB antibodies, thymoma, and GABAB
receptor thymic expression. Neurol Neuroimmunol Neuroinflammation
[Internet]. 2014 Oct 29 [cited 2014 Dec 4];1(4). Available from:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215391/