Paraneoplastic autoimmune encephalitis associated with CV2/CRMP-5 IgG antineuronal antibodies in a patient with thymoma

Werry, C.; Götz, Friedrich; Wurster, Ulrich; Stangel, Martin; Giess, Ralf; Heidenreich, Fedor; Windhagen, Anja

doi:10.1007/s00415-009-0826-1

Cited by 13 publications

(16 citation statements)

References 7 publications

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“…MRI obtained early in the course of disease may be normal, though tends to show multifocal T 2 hyperintensity in non-limbic cortex with little or no enhancement (Figure 9). 95,96 Those patients presenting with hyperkinetic movements often have asymmetric T 2 hyperintensity in the caudate and putamen, usually without enhancement. [97][98][99] Patients with LE can demonstrate T 2 hyperintensity and enlargement of the MTL.…”

Section: Antibodies Targeting Intracellular Neuronal Proteinsmentioning

confidence: 99%

Autoimmune epilepsy: findings on MRI and FDG-PET

Guerin

Watson

Carr

et al. 2018

The British Journal of Radiology

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Although autoimmune epilepsy (AE) is a relatively new concept in the radiology literature, evidence for immunological mechanisms in epilepsy has increased in the last several years. 1-9 AE was originally described in the context of more generalized autoimmune encephalopathy, predominately as a paraneoplastic phenomenon targeting the limbic system. Certain tumors expressing neuronal proteins were found to provoke a cell-mediated neurological disorder as a byproduct of an attack on cancer cells. The classically described paraneoplastic limbic encephalitis (LE) reflects involvement of limbic structures including the anteromedial temporal lobe, hippocampus and amygdala and is clinically characterized by the subacute onset of temporal lobe seizures, anterograde memory impairment and psychiatric symptoms. Similar to other paraneoplastic syndromes, neurologic symptoms can present well before a cancer is detectable. Antibodies traditionally considered paraneoplastic include anti-Hu (ANNA-1) and anti CRMP-5 antibodies, usually found in conjunction with small cell lung carcinoma (SCLC), and anti-N-methyl-Daspartate (NMDA) receptor antibodies which are often associated with ovarian teratoma.

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Section: Antibodies Targeting Intracellular Neuronal Proteinsmentioning

confidence: 99%

Autoimmune epilepsy: findings on MRI and FDG-PET

Guerin

Watson

Carr

et al. 2018

The British Journal of Radiology

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“…Like all the CRMP family members, it is highly expressed in the developing brain as well as regions of neurogenesis of the adult brain (Fukada et al 2000;Charrier et al 2003). CRMP-5 itself has been identified as a biomarker in neuroendocrine lung cancer (Meyronet et al 2008), while CRMP-5 autoantibodies (also named CV2) are known markers for paraneoplastic neurological syndromes and associated cancers, for example, small-cell lung cancer and thymoma (Yu et al 2001;Rogemond and Honnorat 2000;Werry et al 2009). Furthermore, CRMP-5 was shown to be induced as a result of neurotoxicity (Berg et al 2011) supporting its proposed role in neurogenesis.…”

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confidence: 99%

Insights into the oligomerization of CRMPs: crystal structure of human collapsin response mediator protein 5

Ponnusamy

Lohkamp

2013

Journal of Neurochemistry

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Collapsin response mediator protein-5 (CRMP-5) is the latest identified member of the CRMP cytosolic phosphoprotein family, which is crucial for neuronal development and repair. CRMPs exist as homo-and/or hetero-tetramers in vivo and participate in signaling transduction, cytoskeleton rearrangements, and endocytosis. CRMP-5 antagonizes many of the other CRMPs' functions either by directly interacting with them or by competing for their binding partners. We determined the crystal structures of a full length and a truncated version of human CRMP-5, both of which form a homo-tetramer similar to those observed in CRMP-1 and CRMP-2. However, solution studies indicate that CRMP-5 and CRMP-1 form weaker homo-tetramers compared with CRMP-2, and that divalent cations, Ca 2+ and Mg 2+, destabilize oligomers of CRMP-5 and CRMP-1, but promote CRMP-2 oligomerization. On the basis of comparative analysis of the CRMP-5 crystal structure, we identified residues that are crucial for determining the preference for hetero-oligomer or homo-oligomer formation. We also show that in spite of being the CRMP family member most closely related to dihydropyrimidinase, CRMP-5 does not have any detectable amidohydrolase activity. The presented findings provide new detailed insights into the structure, oligomerization, and regulation of CRMPs.

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“…Therefore, even though a paraneoplastic antibody was not positively identified, this case meets diagnostic criteria for definite PNS 1 Ten cases of paraneoplastic encephalitis extending beyond the limbic system have been described in association with a thymoma (Table 1). 3,[7][8][9][10][11][12][13][14][15] Of these cases only four exclusively involved the extra-limbic system. 3,[7][8][9] Similar to all other cases of limbic and extralimbic paraneoplastic encephalitis with a thymoma our patient had confusion, memory disruption, seizures, and non-enhancing bilateral lesions on MRI (Table 1).…”

Section: Discussionmentioning

confidence: 99%

Paraneoplastic limbic and extra-limbic encephalitis secondary to a thymoma mimicking an acute stroke

Reginold

Ninan

Coret-Simon

et al. 2016

Can. J. Neurol. Sci.

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Paraneoplastic neurological syndromes (PNS) occur in one in ten thousand patients with malignancy.1 These syndromes are defined by dysfunction remote from the tumor site that cannot be explained by metastasis, treatment or infection. 2 The dysfunction in PNS is believed to be a result of neoplastic immune-mediated injury to neural tissue. Antibodies may be created against proteins on cancer cells that are usually only expressed in the nervous system. Paraneoplastic neurological syndrome is thought to develop when these antibodies cross-react and trigger an autoimmune response in normal neural tissue.2 Presence of onconeural antibodies, clinical onset around the diagnosis of cancer and improvement with treatment of the cancer favors the diagnosis of PNS. Thymoma is a common anterior mediastinal malignancy. Approximately 40% of cases of thymoma are associated with PNS. 3 The most common and well-known form of PNS in patients with thymoma is myasthenia gravis (MG). In MG the thymus can be the antigenic source for antibodies that disrupt neurotransmission. 4 The most common antibodies found in MG are against the postsynaptic acetylcholine receptor or the muscle specific tyrosine kinase 4 Around 15% of patients with a thymoma have a paraneoplastic process other than myasthenia gravis.3 Paraneoplastic involvement of the central nervous system is an uncommon and less recognized presentation of thymoma. We report a rare case of limbic and extra-limbic paraneoplastic encephalitis with a thymoma. CASE REPORTA 47-year old male presented at the emergency room of a teaching tertiary care hospital with a two-day history of psychotic symptoms consisting of hallucinations, delusions, false memories and disorganized behavior. Patient had past medical history of fatigable weakness limited to the eyelids or extraocular muscles for six months and a brief psychotic episode 20 years earlier. On examination his oxygen saturation was 92% at room air (venous blood gas pH 7.4, pCO 2 40 mmHg, HCO 3 25 mEq/L). He had frontal release signs including positive involuntary grasp and a positive Luria's test. An unenhanced computed tomography (CT) brain scan was performed and demonstrated a left-sided 12mm hypodense lesion in the frontal lobe (Figure 1a). This was interpreted as suspicious for an acute infarction. The patient was admitted to hospital under the Neurology service and had worsening psychotic symptoms. On day six, an unenhanced CT brain scan was repeated and demonstrated progression of the leftsided hypodense lesion that was interpreted as compatible with an evolving infarct (Figure 1b). Based on the results of this CT brain scan, a magnetic resonance imaging (MRI) scan of the brain was not immediately ordered.On day 11, carotid Doppler and transthoracic echocardiography did not reveal any cardiovascular abnormality, but transthoracic echocardiography did demonstrate a large extracardiac mass. On day 14, contrast-enhanced CT of the thorax confirmed an 11 × 10 × 8 cm mediastinal mass lateral to the left border of the heart with soft ...

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Paraneoplastic autoimmune encephalitis associated with CV2/CRMP-5 IgG antineuronal antibodies in a patient with thymoma

Cited by 13 publications

References 7 publications

Autoimmune epilepsy: findings on MRI and FDG-PET

Autoimmune epilepsy: findings on MRI and FDG-PET

Insights into the oligomerization of CRMPs: crystal structure of human collapsin response mediator protein 5

Paraneoplastic limbic and extra-limbic encephalitis secondary to a thymoma mimicking an acute stroke

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