Letters to Editor
References 1. Kanpolat Y, Savas A, Bekar A, Berk C. Percutaneous controlled radiofrequency trigeminal rhizotomy for the treatment of idiopathic trigeminal neuralgia: 25 year experience with 1600 patients. Neurosurgery 2001;48:524‑34. 2. Gilden D, Cohrs RJ, Mahalingam R, Nagel MA. Varicella zoster virus vasculopathies: Diverse clinical manifestations, laboratory features, pathogenesis and treatment. Lancet Neurol 2009;8:731‑40. 3. Burgoon MP, Hammack BN, Owens GP, Maybach AL, Eikelenboom MJ, Gilden DH. Oligoclonal immunoglobulins in cerebro‑spinal fluid during varicella zoster virus (VZV) vasculopathy are directed against VZV. Ann Neurol 2003;54:459‑63. 4. Nagel MA, Forghani B, Mahalingam R, Wellish MC, Cohrs RJ, Russman AN, et al. The value of detecting anti‑VZV IgG antibody in CSF to diagnose VZV vasculopathy. Neurology 2007;68:1069‑73. 5. Nau R, Lantsch M, Stiefel M, Polak T, Reiber H. Varicella zoster virus‑associated focal vasculitis without herpes zoster: Recovery after treatment with acyclovir. Neurology 1998;51:914‑5. Access this article online Quick Response Code:
Website: www.neurologyindia.com PMID: *** DOI: 10.4103/0028-3886.137017
Received: 17-02-2014 Review completed: 24‑02‑2014 Accepted: 03‑06‑2014
Orbital infantile fibrosarcoma presenting as intraconal mass in a 2‑year‑old child: A case report Sir, Infantile/congenital fibrosarcoma is a malignant soft tissue tumor arising from fibroblasts, and its orbital location in infancy is extremely rare presentation.[1] It accounts for 5-10% of all sarcomas in children younger than 1 year.[2] This tumor has also been diagnosed during pregnancy and in a fetus.[3] Orbital infantile fibrosarcoma is attached to the posterior pole of the globe and is uncapsulated at its posterior wall with fibrous tissue similar to the sclera. The tumor may infiltrate the posterior pole of the globe and the optic nerve sheath. Based on these observations, it is thought to have developed in the scleral stroma.[4] A 2‑year‑old male child presented with gradually progressive proptosis of right eye since 6 months. On examination, there was forward and downward protrusion of the eyeball and resistance on retropulsion
322
present. Magnetic resonance imaging (MRI) showed an enhancing mass predominantly in intraconal compartment of right orbit with non‑visualization of superior rectus. Ultrasonography (USG)‑guided fine needle aspiration (FNA) cytology showed clusters and singly scattered spindle to oblong cells with high N:C ratio, hyperchromatic irregular elongated nuclei, inconspicuous nucleoli and scant to moderate cytoplasm on a background of myxoid material, and hemorrhage. Cellblock of the USG‑guided FNA material showed sheets of spindle‑shaped cells with typical herring bone pattern [Figure 1]. The patient underwent surgery, and operative findings showed a friable, globular and well‑encapsulated intraconal mass (3 × 3 × 2 cm). Grossly, mass was globular and grayish white on cut surface. Histopathologic examination showed a highly cellular mesenchymal tumor with spindle‑shaped nuclei, condensed chromatin, inconspicuous nucleoli, and scant to moderate amount of cytoplasm. Tumor cells were arranged in fascicles and had a characteristic herring bone pattern [Figure 2]. The mitotic count was 4/10 hpf (high power fields). Immunohistochemistry was strongly positive for vimentin and negative for desmin, myogenin, Smooth muscle actin (SMA), S100, Bcl2, CD117, Anaplastic lymphoma kinase 1 (ALK1), CD34, HMB 45, Epithelial membrane antigen (EMA), CD99 and Cytokeratin (CK), confirming the diagnosis of infantile fibrosarcoma [Figure 3], indicating that the tumor had originated from mesodermal cells, high Ki 67 index (12-15%) [Figure 4] and herringbone patterns. After 6 month of follow up, our patient is well and active. No recurrence has been noted after surgical resection of orbital mass. Only a few cases of histologically verified infantile fibrosarcoma of the orbit on have been described.[5‑8] Some fibrosarcomas in previous reports were described as non‑encapsulated or poorly circumscribed. The cytomorphological differential diagnosis [Table 1] includes soft tissue sarcomas like spindle cell rhabdomyosarcoma (positive for desmin or myogenin), solitary fibrous tumor (positive for S100 and Bcl2), leiomyosarcoma (positive for SMA), schwannoma/ malignant peripheral nerve sheath tumor (S100), fibrohistiocytic tumor (CD34), extra‑gastrointestinal stromal tumor (CD117), inflammatory myofibroblastic tumor (ALK‑1), sarcomatoid carcinoma (CK), synovial sarcoma (EMA, CD99), infantile myofibroma (vimentin and S100) and infantile fibromatosis (B‑catenin). Other study showed infantile fibrosarcoma tumor cells revealed diffusely positive for vimentin and focal positivity for actin but are negative for S100, desmin, and myoglobin. Although histologically similar to fibrosarcomas occurring in adults, the Neurology India | May-Jun 2014 | Vol 62 | Issue 3
Letters to Editor
congenital lesions differ in their clinical behavior. Metastasis is rare but less than 10% and local recurrence is common. Compared with adult fibrosarcoma, congenital fibrosarcoma has slower growth rate and
Figure 1: Cellblock showed sheets of spindle-shaped cells with typical herring bone pattern. (hematoxylin and eosin, H and E; ×20 magnification)
Figure 2: Histopathology section shows sheets of atypical spindleshaped cells with elongated hyperchromatic nuclei, condensed chromatin, inconspicuous nucleoli, and moderate cytoplasm with characteristic herring bone pattern (H and E, ×40 magnification)
better prognosis.[9] A study revealed a high degree of cellularity, rapid growth, and extensive local invasion; metastases are rare and occur mostly in the lungs, bones, and sometimes in the lymph nodes. Local recurrence is noted and occurs in 20-40% of cases.[10]
Figure 3: Immunohistochemistry showed tumor cells with strongly positive for vimentin (Vimentin ×40 magnification)
Figure 4: Ki-67 showed 12-15% of nuclear proliferating index (Ki-67, ×40 magnification)
Table 1: Immunohistochemical findings in differential diagnosis of infantile fibrosarcoma in orbit
Types of tumors
Immunohistochemical findings Molecular analysis VIM CD34 S100 SMA Desmin Myogenin BCL2 CD117 ALK1 CK
Solitary fibrous tumor Rhabdomyosarcoma Leiomyoma/Leiomyosarcoma Schwannoma/MPNST Gastrointestinal stromal tumor Fibrohistiocytic tumor Inflammatory myofibroblastic tumor Sarcomatoid carcinoma Infantile myofibroma Fibrosarcoma
+/− ++ + +/− ++ + + +/− + +
+ ‑ ‑ + ++ + ‑ ‑ ‑ +/‑
‑ ‑ ‑ ++ +/− ‑ ‑ ‑ ‑ ‑
‑ ‑ + ‑ ‑ ‑ + ‑ +/‑ ‑
‑ ++ +/− ‑ +/− ‑ ‑ ‑ ‑ ‑
‑ ++ ‑ ‑ ‑ ‑ ‑ ‑ ‑ ‑
+ ‑ ‑ ‑ ‑ ‑ ‑ ‑ ‑ ‑
‑ ‑ ‑ ‑ +++ ‑ ‑ ‑ ‑ ‑
‑ ‑ ‑ ‑ ‑ ‑ ++ ‑ ‑ ‑
‑ ‑ ‑ ‑ ‑ ‑ ‑ ++ ‑ ‑
‑ ‑ MD‑M2 and CDK4 mutations ‑ c‑KIT or PDGFRA mutations ‑ ALK1 mutations ‑ ETV6‑NTRK genefusion ‑
VIM - Vimentin; SMA - Smooth muscle actin; ALK1 - Anaplastic lymphoma Kinase‑1; CK - Cytokeratin
Neurology India | May-Jun 2014 | Vol 62 | Issue 3
323
Letters to Editor
Ram Nawal Rao, Megha Bansal, Shivanjali Raghuvanshi, Deepti Mishra Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India Email: [email protected]
References 1. 2.
3.
4. 5. 6. 7. 8.
9. 10.
Tarik E, Lamiae R, Abdelouahed A, Tarik M, Hassan G, Anouar DM. Unusual case of congenital/infantile fibrosarcoma in a new born. Afr J Paediatr Surg 2013;10:185‑7. Akyaaz C, Sari N, Vargel I, Gedikoglu G, Haliloglu M, Büyükpamukçu M. A newborn with infantile fibrosarcoma of foot: Treatment with chemotherapy and extremity–sparing surgery. J Perinatol 2010;30:63‑5. Kodet R, Stejskal J, Pilat D, Kocourková M, Smelhaus V, Eckschlager T. Congenital‑infantile fibrosarcoma: A clinicopathogical study of five patients entered on the prague children’s tumour registry. Pathol Res Pract. 1996;192:845-50. Ohtsuka K, Saito K. Primary orbital fibrosarcoma developing in the scleral stroma. British Journal of Ophthalmology. 1996;80:932-3. Yanoff M, Scheie HG. Fibrosarcoma of orbit. Report of two patients. Cancer 1966;19:1711‑6. Jakobiec FA, Tannenbaum M. The ultrastructure of orbital fibrosarcoma. Am J Ophthalmol 1974;77:899‑917. Scott SM, Reiman HM, Pritchard DJ, IIstrup DM. Soft tissue fibrosarcoma. A clinicopathologic study of 132 cases. Cancer 1989;64:925‑31. Tsang HH, Dolman PJ, Courtemanche DJ, Rassekh SR, Senger C, Lyons CJ. Prenatal presentation of fronto‑orbital congenital infantile fibrosarcoma: A clinicopathologic report. JAMA Ophthalmol 2013;131:965‑7. Weiss SW. Congenital and Infantile fibrosarcoma. In: Enzinger FM, Weiss SW, editors. Soft Tissue Tumours. 4th ed. Missouri: Mosby Elsevier; 2001. p. 377‑9. Rosai J, Ackerman LV. Surgical Pathology. Newyork: Mosby Elsevier; 2004. p. 2253. Access this article online Quick Response Code:
Website: www.neurologyindia.com PMID: *** DOI: 10.4103/0028-3886.137018
Received: 29-01-2014 Review completed: 04-03-2014 Accepted: 29-05-2014
Anti NMDA receptor encephalitis associated with thymic hyperplasia: A case report Sir, Anti‑N‑methyl-D‑aspartate receptor (NMDAR) 324
encephalitis is a rare disorder associated with antibodies against the NR1/NR2 heteromers of NMDAR and resulting in a characteristic neuropsychiatric syndrome.[1] Thymic hyperplasia is often detected in myasthenia gravis patients, but its association with autoimmune encephalitis is quite uncommon. To our knowledge, this is the first report of anti‑NMDA receptor encephalitis presenting with thymic hyperplasia. NMDAR expression in the thymic tissue suggests that thymus might be involved in autoimmune encephalitis pathogenesis. A 23‑year‑old woman was admitted with sleep onset seizures and behavioral changes. Neurological examination showed somnolence, disorientation, spontaneous eye movements with no side restriction. In the following days, she continued having multiple generalized tonic‑clonic convulsions, as well as involuntary leg movements, oropharyngeal automatisms, confusion, aggression, dysarthria and stupor. Cranial magnetic resonance imaging (MRI) revealed gyral swelling, T2‑FLAIR signal increase and diffusion restriction in the left parahippocampal and temporooccipital regions with no contrast enhancement [Figure 1]. The electroencephalogram (EEG) showed diffuse theta waves. Cerebrospinal fluid (CSF) examination was normal. Anti‑NMDAR IgG and IgA antibodies were detected in serum and CSF by a commercial kit (Euroimmun, Luebeck, Germany), whereas antibodies to other well‑characterized onconeural and ion‑channel antigens were negative. Computed tomography (CT) scanning of the abdomen/pelvis and (18) F‑FDG PET/CT were normal. The thorax MRI revealed thymic hyperplasia. Pathological examination of the thymus after thymectomy showed hyperplasia but no signs of teratoma or any other neoplasms. Immunofluorescence studies showed an intense expression of NR1 and NR2 subunits of NMDAR in hyperplastic thymus tissue. Double immunolabeling performed with anti‑CD3 (1:1000, Santa Cruz, CA, USA) and anti‑NR1 or anti‑NR2 (both 1:500, Santa Cruz) antibodies and appropriate ALEXA‑conjugated secondary antibodies (1:1000, Invitrogen, CA, USA)[1] showed a significant colocalization [Figure 2]. No appreciable NR1/NR2 expression was observed in non‑CD3+ cells. Plasmapheresis significantly improved symptoms and reduced seizure frequency. No relapses were recorded in 2 years of follow‑up and repeat imaging studies failed to show any tumors. While it is conceivable that NMDARs expressed by tumor cells might trigger anti‑neuronal autoimmunity, mechanisms by which anti‑NMDAR encephalitis emerges in patients with no tumors are unclear. Expression and Neurology India | May-Jun 2014 | Vol 62 | Issue 3
Copyright of Neurology India is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
References 1. Kanpolat Y, Savas A, Bekar A, Berk C. Percutaneous controlled radiofrequency trigeminal rhizotomy for the treatment of idiopathic trigeminal neuralgia: 25 year experience with 1600 patients. Neurosurgery 2001;48:524‑34. 2. Gilden D, Cohrs RJ, Mahalingam R, Nagel MA. Varicella zoster virus vasculopathies: Diverse clinical manifestations, laboratory features, pathogenesis and treatment. Lancet Neurol 2009;8:731‑40. 3. Burgoon MP, Hammack BN, Owens GP, Maybach AL, Eikelenboom MJ, Gilden DH. Oligoclonal immunoglobulins in cerebro‑spinal fluid during varicella zoster virus (VZV) vasculopathy are directed against VZV. Ann Neurol 2003;54:459‑63. 4. Nagel MA, Forghani B, Mahalingam R, Wellish MC, Cohrs RJ, Russman AN, et al. The value of detecting anti‑VZV IgG antibody in CSF to diagnose VZV vasculopathy. Neurology 2007;68:1069‑73. 5. Nau R, Lantsch M, Stiefel M, Polak T, Reiber H. Varicella zoster virus‑associated focal vasculitis without herpes zoster: Recovery after treatment with acyclovir. Neurology 1998;51:914‑5. Access this article online Quick Response Code:
Website: www.neurologyindia.com PMID: *** DOI: 10.4103/0028-3886.137017
Received: 17-02-2014 Review completed: 24‑02‑2014 Accepted: 03‑06‑2014
Orbital infantile fibrosarcoma presenting as intraconal mass in a 2‑year‑old child: A case report Sir, Infantile/congenital fibrosarcoma is a malignant soft tissue tumor arising from fibroblasts, and its orbital location in infancy is extremely rare presentation.[1] It accounts for 5-10% of all sarcomas in children younger than 1 year.[2] This tumor has also been diagnosed during pregnancy and in a fetus.[3] Orbital infantile fibrosarcoma is attached to the posterior pole of the globe and is uncapsulated at its posterior wall with fibrous tissue similar to the sclera. The tumor may infiltrate the posterior pole of the globe and the optic nerve sheath. Based on these observations, it is thought to have developed in the scleral stroma.[4] A 2‑year‑old male child presented with gradually progressive proptosis of right eye since 6 months. On examination, there was forward and downward protrusion of the eyeball and resistance on retropulsion
322
present. Magnetic resonance imaging (MRI) showed an enhancing mass predominantly in intraconal compartment of right orbit with non‑visualization of superior rectus. Ultrasonography (USG)‑guided fine needle aspiration (FNA) cytology showed clusters and singly scattered spindle to oblong cells with high N:C ratio, hyperchromatic irregular elongated nuclei, inconspicuous nucleoli and scant to moderate cytoplasm on a background of myxoid material, and hemorrhage. Cellblock of the USG‑guided FNA material showed sheets of spindle‑shaped cells with typical herring bone pattern [Figure 1]. The patient underwent surgery, and operative findings showed a friable, globular and well‑encapsulated intraconal mass (3 × 3 × 2 cm). Grossly, mass was globular and grayish white on cut surface. Histopathologic examination showed a highly cellular mesenchymal tumor with spindle‑shaped nuclei, condensed chromatin, inconspicuous nucleoli, and scant to moderate amount of cytoplasm. Tumor cells were arranged in fascicles and had a characteristic herring bone pattern [Figure 2]. The mitotic count was 4/10 hpf (high power fields). Immunohistochemistry was strongly positive for vimentin and negative for desmin, myogenin, Smooth muscle actin (SMA), S100, Bcl2, CD117, Anaplastic lymphoma kinase 1 (ALK1), CD34, HMB 45, Epithelial membrane antigen (EMA), CD99 and Cytokeratin (CK), confirming the diagnosis of infantile fibrosarcoma [Figure 3], indicating that the tumor had originated from mesodermal cells, high Ki 67 index (12-15%) [Figure 4] and herringbone patterns. After 6 month of follow up, our patient is well and active. No recurrence has been noted after surgical resection of orbital mass. Only a few cases of histologically verified infantile fibrosarcoma of the orbit on have been described.[5‑8] Some fibrosarcomas in previous reports were described as non‑encapsulated or poorly circumscribed. The cytomorphological differential diagnosis [Table 1] includes soft tissue sarcomas like spindle cell rhabdomyosarcoma (positive for desmin or myogenin), solitary fibrous tumor (positive for S100 and Bcl2), leiomyosarcoma (positive for SMA), schwannoma/ malignant peripheral nerve sheath tumor (S100), fibrohistiocytic tumor (CD34), extra‑gastrointestinal stromal tumor (CD117), inflammatory myofibroblastic tumor (ALK‑1), sarcomatoid carcinoma (CK), synovial sarcoma (EMA, CD99), infantile myofibroma (vimentin and S100) and infantile fibromatosis (B‑catenin). Other study showed infantile fibrosarcoma tumor cells revealed diffusely positive for vimentin and focal positivity for actin but are negative for S100, desmin, and myoglobin. Although histologically similar to fibrosarcomas occurring in adults, the Neurology India | May-Jun 2014 | Vol 62 | Issue 3
Letters to Editor
congenital lesions differ in their clinical behavior. Metastasis is rare but less than 10% and local recurrence is common. Compared with adult fibrosarcoma, congenital fibrosarcoma has slower growth rate and
Figure 1: Cellblock showed sheets of spindle-shaped cells with typical herring bone pattern. (hematoxylin and eosin, H and E; ×20 magnification)
Figure 2: Histopathology section shows sheets of atypical spindleshaped cells with elongated hyperchromatic nuclei, condensed chromatin, inconspicuous nucleoli, and moderate cytoplasm with characteristic herring bone pattern (H and E, ×40 magnification)
better prognosis.[9] A study revealed a high degree of cellularity, rapid growth, and extensive local invasion; metastases are rare and occur mostly in the lungs, bones, and sometimes in the lymph nodes. Local recurrence is noted and occurs in 20-40% of cases.[10]
Figure 3: Immunohistochemistry showed tumor cells with strongly positive for vimentin (Vimentin ×40 magnification)
Figure 4: Ki-67 showed 12-15% of nuclear proliferating index (Ki-67, ×40 magnification)
Table 1: Immunohistochemical findings in differential diagnosis of infantile fibrosarcoma in orbit
Types of tumors
Immunohistochemical findings Molecular analysis VIM CD34 S100 SMA Desmin Myogenin BCL2 CD117 ALK1 CK
Solitary fibrous tumor Rhabdomyosarcoma Leiomyoma/Leiomyosarcoma Schwannoma/MPNST Gastrointestinal stromal tumor Fibrohistiocytic tumor Inflammatory myofibroblastic tumor Sarcomatoid carcinoma Infantile myofibroma Fibrosarcoma
+/− ++ + +/− ++ + + +/− + +
+ ‑ ‑ + ++ + ‑ ‑ ‑ +/‑
‑ ‑ ‑ ++ +/− ‑ ‑ ‑ ‑ ‑
‑ ‑ + ‑ ‑ ‑ + ‑ +/‑ ‑
‑ ++ +/− ‑ +/− ‑ ‑ ‑ ‑ ‑
‑ ++ ‑ ‑ ‑ ‑ ‑ ‑ ‑ ‑
+ ‑ ‑ ‑ ‑ ‑ ‑ ‑ ‑ ‑
‑ ‑ ‑ ‑ +++ ‑ ‑ ‑ ‑ ‑
‑ ‑ ‑ ‑ ‑ ‑ ++ ‑ ‑ ‑
‑ ‑ ‑ ‑ ‑ ‑ ‑ ++ ‑ ‑
‑ ‑ MD‑M2 and CDK4 mutations ‑ c‑KIT or PDGFRA mutations ‑ ALK1 mutations ‑ ETV6‑NTRK genefusion ‑
VIM - Vimentin; SMA - Smooth muscle actin; ALK1 - Anaplastic lymphoma Kinase‑1; CK - Cytokeratin
Neurology India | May-Jun 2014 | Vol 62 | Issue 3
323
Letters to Editor
Ram Nawal Rao, Megha Bansal, Shivanjali Raghuvanshi, Deepti Mishra Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India Email: [email protected]
References 1. 2.
3.
4. 5. 6. 7. 8.
9. 10.
Tarik E, Lamiae R, Abdelouahed A, Tarik M, Hassan G, Anouar DM. Unusual case of congenital/infantile fibrosarcoma in a new born. Afr J Paediatr Surg 2013;10:185‑7. Akyaaz C, Sari N, Vargel I, Gedikoglu G, Haliloglu M, Büyükpamukçu M. A newborn with infantile fibrosarcoma of foot: Treatment with chemotherapy and extremity–sparing surgery. J Perinatol 2010;30:63‑5. Kodet R, Stejskal J, Pilat D, Kocourková M, Smelhaus V, Eckschlager T. Congenital‑infantile fibrosarcoma: A clinicopathogical study of five patients entered on the prague children’s tumour registry. Pathol Res Pract. 1996;192:845-50. Ohtsuka K, Saito K. Primary orbital fibrosarcoma developing in the scleral stroma. British Journal of Ophthalmology. 1996;80:932-3. Yanoff M, Scheie HG. Fibrosarcoma of orbit. Report of two patients. Cancer 1966;19:1711‑6. Jakobiec FA, Tannenbaum M. The ultrastructure of orbital fibrosarcoma. Am J Ophthalmol 1974;77:899‑917. Scott SM, Reiman HM, Pritchard DJ, IIstrup DM. Soft tissue fibrosarcoma. A clinicopathologic study of 132 cases. Cancer 1989;64:925‑31. Tsang HH, Dolman PJ, Courtemanche DJ, Rassekh SR, Senger C, Lyons CJ. Prenatal presentation of fronto‑orbital congenital infantile fibrosarcoma: A clinicopathologic report. JAMA Ophthalmol 2013;131:965‑7. Weiss SW. Congenital and Infantile fibrosarcoma. In: Enzinger FM, Weiss SW, editors. Soft Tissue Tumours. 4th ed. Missouri: Mosby Elsevier; 2001. p. 377‑9. Rosai J, Ackerman LV. Surgical Pathology. Newyork: Mosby Elsevier; 2004. p. 2253. Access this article online Quick Response Code:
Website: www.neurologyindia.com PMID: *** DOI: 10.4103/0028-3886.137018
Received: 29-01-2014 Review completed: 04-03-2014 Accepted: 29-05-2014
Anti NMDA receptor encephalitis associated with thymic hyperplasia: A case report Sir, Anti‑N‑methyl-D‑aspartate receptor (NMDAR) 324
encephalitis is a rare disorder associated with antibodies against the NR1/NR2 heteromers of NMDAR and resulting in a characteristic neuropsychiatric syndrome.[1] Thymic hyperplasia is often detected in myasthenia gravis patients, but its association with autoimmune encephalitis is quite uncommon. To our knowledge, this is the first report of anti‑NMDA receptor encephalitis presenting with thymic hyperplasia. NMDAR expression in the thymic tissue suggests that thymus might be involved in autoimmune encephalitis pathogenesis. A 23‑year‑old woman was admitted with sleep onset seizures and behavioral changes. Neurological examination showed somnolence, disorientation, spontaneous eye movements with no side restriction. In the following days, she continued having multiple generalized tonic‑clonic convulsions, as well as involuntary leg movements, oropharyngeal automatisms, confusion, aggression, dysarthria and stupor. Cranial magnetic resonance imaging (MRI) revealed gyral swelling, T2‑FLAIR signal increase and diffusion restriction in the left parahippocampal and temporooccipital regions with no contrast enhancement [Figure 1]. The electroencephalogram (EEG) showed diffuse theta waves. Cerebrospinal fluid (CSF) examination was normal. Anti‑NMDAR IgG and IgA antibodies were detected in serum and CSF by a commercial kit (Euroimmun, Luebeck, Germany), whereas antibodies to other well‑characterized onconeural and ion‑channel antigens were negative. Computed tomography (CT) scanning of the abdomen/pelvis and (18) F‑FDG PET/CT were normal. The thorax MRI revealed thymic hyperplasia. Pathological examination of the thymus after thymectomy showed hyperplasia but no signs of teratoma or any other neoplasms. Immunofluorescence studies showed an intense expression of NR1 and NR2 subunits of NMDAR in hyperplastic thymus tissue. Double immunolabeling performed with anti‑CD3 (1:1000, Santa Cruz, CA, USA) and anti‑NR1 or anti‑NR2 (both 1:500, Santa Cruz) antibodies and appropriate ALEXA‑conjugated secondary antibodies (1:1000, Invitrogen, CA, USA)[1] showed a significant colocalization [Figure 2]. No appreciable NR1/NR2 expression was observed in non‑CD3+ cells. Plasmapheresis significantly improved symptoms and reduced seizure frequency. No relapses were recorded in 2 years of follow‑up and repeat imaging studies failed to show any tumors. While it is conceivable that NMDARs expressed by tumor cells might trigger anti‑neuronal autoimmunity, mechanisms by which anti‑NMDAR encephalitis emerges in patients with no tumors are unclear. Expression and Neurology India | May-Jun 2014 | Vol 62 | Issue 3
Copyright of Neurology India is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
