- Email: [email protected]
Plexiform neurolymphomatosis
328
revue neurologique 172 (2016) 324–334
[2] Didelot A, Serratrice J, Honnorat J, Serratrice G. Ence´phalites limbiques. In: EMC Neurologie. Paris: Elsevier Masson SAS; 2011 [17-059-K-13]. [3] Leypoldt F, Wandinger KP, Bien CG, Dalmau J. Autoimmune encephalitis. Eur Neurol Rev 2013;8(1):31–7. [4] Ozkan M, Aksoy A, C¸enesiz F, Atay NE, Yu¨ksel D. The association of anti-glutamic acid decarboxylase antibodies with different neurological findings in childhood. Epilepsy Behav 2012;25:464–7. [5] Striano P, Errichiello L, Striano S. Autoantibodies to glutamic acid decarboxylase in patients with epilepsy: what is their clinical relevance? Epilepsy Behav 2011;20:146. [6] Blanc F, Ruppert E, Kleitz C, Valenti MP, Cretin B, Humbel RL, et al. Acute limbic encephalitis and glutamic acid decarboxylase antibodies: a reality? J Neurol Sci 2009;287: 69–71.
Fig. 1 – Brain magnetic resonance imaging.
was supported by the absence of any sign of malignancy, the negative search for onconeuronal antibodies, and the presence of anti-GAD antibodies. Well known as biomarkers of type I diabetes, anti-GAD antibodies were attributed to LE in our patient because of their intratecal distribution and the very high serum level. Anti-GAD auto-antibody LE is a very rare entity. It is probably under-diagnosed and its incidence is unknown [1,3]. In one study of 233 epileptic patients, the authors identified four patients with anti-GAD antibodies associated with temporal seizures [1]. Our case is unusual because of the onset at a very young age while peak onset has been described around 23 years, with clear female predominance [3,4]. In most cases [4,5], memory disorders or epileptic seizures are severe and proportionally correlated with antiGAD antibodies in serum and/or CSF. Approximately 60% of cases involve a stiff man syndrome and cerebellous ataxia [2,3,5] that were not observed in our patient. Etiopathogenic treatment is based on corticosteroid therapy, immunoglobulins, or plasmapheresis [5,6]. In resistant forms, cyclophosphamids are proposed [4]. LE is a dysimmune disorder that responds well to therapeutic management if the diagnosis is established early.
Disclosure of interest The authors declare that they have no competing interest.
references
[1] Cartalat-Carel S, Leston N, Ducray F, Rogemond V, Honnorat J. Les ence´phalites limbiques, un syndrome mal connu et sous diagnostique´. Psychol Neuropsychiatr Vieil 2008;6(3):209–18.
A. M’zahema,*,b A. Meziania N. Taghanea,b A. Boulefkhada,b S. Khellafa A. Hamria,b a Service de neurologie, centre hospitalo-universitaire Benbadis, rue Benseghir Abdelouahab, 25000 Constantine, Algeria b Laboratoire de ge´ne´tique et de biologie mole´culaire, universite´ Constantine 3, 25000 Constantine, Algeria *Corresponding author. E-mail address: [email protected] (A. M’zahem) Received 10 November Received in revised form 8 February Accepted 15 February Available online 23 April
2015 2016 2016 2016
http://dx.doi.org/10.1016/j.neurol.2016.02.012 0035-3787/# 2016 Elsevier Masson SAS. All rights reserved.
Plexiform neurolymphomatosis In October 2014, a 65-year-old woman with a 5-month history of right-foot sole numbness was referred to our neurological department for electrophysiological studies. Neurological examination showed an inability to curl the toes, foot sole hypoesthesia, and foot and toe dorsal extensor weakness (3/5) on the right side. Strength of the plantar flexors of the right foot was normal. The lower end of the right calf was swollen, and the right Achilles tendon appeared thickened compared with the left one. Ankle reflexes were absent on both sides. Electrophysiological studies revealed the presence of a complete right tibial sensory and motor nerve conduction block behind the medial malleolus (nerve conduction study results: absent distal motor response, absent sensory action potentials of the plantar nerves; abductor hallucis electromyography results: absence of abnormal insertional and spontaneous activity, absence of any voluntary motor unit action potential [MUAP]), and a partial right fibular motor nerve conduction block behind the neck of the fibula
revue neurologique 172 (2016) 324–334
329
Fig. 1 – T2-weighted MRI scans of (A) the right knee, (B) lower leg and (C) ankle. A. There are several hyposignal (compared with muscle) nodular thickenings, 3–3.5 cm in diameter, along deep division branches of the sciatic nerve (short black arrows), and infracentimetric nodular thickenings in subcutaneous nerve branches (long black arrows). B, C. The main trunk of the tibial nerve exhibits diffuse iso/hyposignal thickening (with some focal size variations) along its course in the lower leg and ankle (white arrowheads), and nerve fascicles appear to be dissected by infiltrative tissue extending to nearby adipose and muscle tissues (indicated by x). A, C: axial views; B: coronal view.
330
revue neurologique 172 (2016) 324–334
(motor nerve conduction study results: proximal amplitude reduction of 77%, focal nerve conduction reduced to 16 m/s; tibialis anterior and extensor digitorum longus electromyography results: absence of abnormal insertional and spontaneous activity, reduced MUAP recruitment with no morphological changes). A sural nerve conduction study and electromyography of the medial gastrocnemius muscle were normal. Magnetic resonance imaging (MRI) revealed plexiform neurofibroma-like lesions (Fig. 1). Nodular thickenings of various sizes were found in the popliteal region, along the tibial and fibular divisions of the right sciatic nerve, and along the superficial subcutaneous nerves. More distally, the main trunk of the tibial nerve was diffusely enlarged, and numerous subcutaneous nerves were also focally thickened. The nerves appeared intact, yet were dissected by partially enhancing infiltrative tissue, which extended along the nearby vascular structures, and adipose and muscle tissues. After further questioning, the patient admitted to a 6-month history of severe weight loss and profuse night sweats. Multiple painless cervical, axillary and inguinal lymph nodes were found on examination. Laboratory tests showed mild anemia, a raised erythrocyte sedimentation rate and raised serum lactate dehydrogenase levels. Whole-body 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) revealed intense FDG uptake along the right sciatic nerve as well as at numerous nodal and extranodal sites. Open biopsy of an easily accessible right inguinal hypermetabolic lymph node was performed and revealed an aggressive B-cell non-Hodgkin’s lymphoma, which was intermediate between diffuse large B-cell lymphoma and Burkitt’s lymphoma. R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy was administered, prompting an initial complete response as assessed by whole-body 18-FDG PET/CT. Unfortunately, a relapse occurred a month after the last course of chemotherapy. Neurolymphomatosis (NL), defined as infiltration of the peripheral nervous system by malignant lymphocytes, is a rare disorder that differs from those commonly associated with leukemia or lymphoma and arises as a result of irradiation or chemotherapy, or as a paraneoplastic effect [1]. In a small proportion of patients, NL may be the first manifestation of disease. In such patients, the diagnosis of NL may be particularly challenging and yet is of crucial importance as it enables appropriate treatment at an early stage of disease. MRI is a highly useful diagnostic tool in NL, having a sensitivity of almost 80% [1]. Roots, plexuses and nerves infiltrated by malignant lymphocytes are enlarged and commonly enhanced on gadolinium administration. In cases of solitary nerve involvement, two patterns have so far been described: localized nerve thickening (pattern 1); and diffuse linear thickening of the main nerve trunk (pattern 2). The present report is of a plexiform pattern (multinodular thickenings of deep and subcutaneous nerves), which differs from any previously reported patterns, and is thus expanding the spectrum of NL radiological presentations and broadening the differential diagnosis of plexiform lesions, which includes neurofibroma, schwannoma, nerve sheath myxoma, perineurioma, fibrohistiocytic tumor, malignant peripheral nerve sheath tumor, spindle cell lipoma, spindle cell nevus and tufted angioma [2–5].
Disclosure of interest The authors declare that they have no competing interest.
Acknowledgement We wish to thank Olivier Beuscart for his help in the preparation of the figures.
references
[1] Grisariu S, Avni B, Batchelor BM, van den Bent MJ, Bokstein F, Schiff D, et al. Neurolymphomatosis: an International Primary CNS Lymphoma Collaborative Group report. Blood 2010;115(24):5005–11. [2] Nishida Y, Tsukushi S, Urakawa H, Arai E, Kozawa E, Ishiguro N. Lower leg compartment syndrome in neurofibromatosis 1 patient with plexiform neurofibrom: a case report aneurysm rupture. Ann Vasc Surg 2014;28(4):1035. [3] Ko JY, Kim JE, Kim YH, Ro YS. Cutaneous plexiform schwannomas in a patient with neurofibromatosis type 2. Ann Dermatol 2009;21(4):402–5. [4] Zelger B, Weinlich G, Steiner H, Zelger BG, Egarter-Vigl E. Dermal and subcutaneous variants of plexiform fibrohistiocytic tumor. Am J Surg Pathol 1997;21(2):235–41. [5] Mentzel T, Kutzner H. Reticular and plexiform perineurioma: clinicopathological and immunohistochemical analysis of two cases and review of perineurial neoplasm of skin and soft tissues. Virchows Arch 2005;447(4):677–82.
R. Denaysa,* V. Baudrezb P. Abouhamadc T. Dere`mec G. Milbouwd J.-P. Hermannee a Department of Neurology, CHR Sambre & Meuse, avenue Albert Ier 185, 5000 Namur, Belgium b Department of Radiology, CHR Sambre & Meuse, avenue Albert Ier 185, 5000 Namur, Belgium c Department of Nuclear Medicine, CHR Sambre & Meuse, avenue Albert Ier 185, 5000 Namur, Belgium d Department of Neurosurgery, CHR Sambre & Meuse, avenue Albert Ier 185, 5000 Namur, Belgium e Department of Hemato-Oncology, CHR Sambre & Meuse, avenue Albert Ier 185, 5000 Namur, Belgium *Corresponding author. E-mail address: [email protected] (R. Denays) Received 9 December 2015 Accepted 18 February 2016 Available online 23 April 2016 http://dx.doi.org/10.1016/j.neurol.2016.02.008 0035-3787/# 2016 Elsevier Masson SAS. All rights reserved.
revue neurologique 172 (2016) 324–334
[2] Didelot A, Serratrice J, Honnorat J, Serratrice G. Ence´phalites limbiques. In: EMC Neurologie. Paris: Elsevier Masson SAS; 2011 [17-059-K-13]. [3] Leypoldt F, Wandinger KP, Bien CG, Dalmau J. Autoimmune encephalitis. Eur Neurol Rev 2013;8(1):31–7. [4] Ozkan M, Aksoy A, C¸enesiz F, Atay NE, Yu¨ksel D. The association of anti-glutamic acid decarboxylase antibodies with different neurological findings in childhood. Epilepsy Behav 2012;25:464–7. [5] Striano P, Errichiello L, Striano S. Autoantibodies to glutamic acid decarboxylase in patients with epilepsy: what is their clinical relevance? Epilepsy Behav 2011;20:146. [6] Blanc F, Ruppert E, Kleitz C, Valenti MP, Cretin B, Humbel RL, et al. Acute limbic encephalitis and glutamic acid decarboxylase antibodies: a reality? J Neurol Sci 2009;287: 69–71.
Fig. 1 – Brain magnetic resonance imaging.
was supported by the absence of any sign of malignancy, the negative search for onconeuronal antibodies, and the presence of anti-GAD antibodies. Well known as biomarkers of type I diabetes, anti-GAD antibodies were attributed to LE in our patient because of their intratecal distribution and the very high serum level. Anti-GAD auto-antibody LE is a very rare entity. It is probably under-diagnosed and its incidence is unknown [1,3]. In one study of 233 epileptic patients, the authors identified four patients with anti-GAD antibodies associated with temporal seizures [1]. Our case is unusual because of the onset at a very young age while peak onset has been described around 23 years, with clear female predominance [3,4]. In most cases [4,5], memory disorders or epileptic seizures are severe and proportionally correlated with antiGAD antibodies in serum and/or CSF. Approximately 60% of cases involve a stiff man syndrome and cerebellous ataxia [2,3,5] that were not observed in our patient. Etiopathogenic treatment is based on corticosteroid therapy, immunoglobulins, or plasmapheresis [5,6]. In resistant forms, cyclophosphamids are proposed [4]. LE is a dysimmune disorder that responds well to therapeutic management if the diagnosis is established early.
Disclosure of interest The authors declare that they have no competing interest.
references
[1] Cartalat-Carel S, Leston N, Ducray F, Rogemond V, Honnorat J. Les ence´phalites limbiques, un syndrome mal connu et sous diagnostique´. Psychol Neuropsychiatr Vieil 2008;6(3):209–18.
A. M’zahema,*,b A. Meziania N. Taghanea,b A. Boulefkhada,b S. Khellafa A. Hamria,b a Service de neurologie, centre hospitalo-universitaire Benbadis, rue Benseghir Abdelouahab, 25000 Constantine, Algeria b Laboratoire de ge´ne´tique et de biologie mole´culaire, universite´ Constantine 3, 25000 Constantine, Algeria *Corresponding author. E-mail address: [email protected] (A. M’zahem) Received 10 November Received in revised form 8 February Accepted 15 February Available online 23 April
2015 2016 2016 2016
http://dx.doi.org/10.1016/j.neurol.2016.02.012 0035-3787/# 2016 Elsevier Masson SAS. All rights reserved.
Plexiform neurolymphomatosis In October 2014, a 65-year-old woman with a 5-month history of right-foot sole numbness was referred to our neurological department for electrophysiological studies. Neurological examination showed an inability to curl the toes, foot sole hypoesthesia, and foot and toe dorsal extensor weakness (3/5) on the right side. Strength of the plantar flexors of the right foot was normal. The lower end of the right calf was swollen, and the right Achilles tendon appeared thickened compared with the left one. Ankle reflexes were absent on both sides. Electrophysiological studies revealed the presence of a complete right tibial sensory and motor nerve conduction block behind the medial malleolus (nerve conduction study results: absent distal motor response, absent sensory action potentials of the plantar nerves; abductor hallucis electromyography results: absence of abnormal insertional and spontaneous activity, absence of any voluntary motor unit action potential [MUAP]), and a partial right fibular motor nerve conduction block behind the neck of the fibula
revue neurologique 172 (2016) 324–334
329
Fig. 1 – T2-weighted MRI scans of (A) the right knee, (B) lower leg and (C) ankle. A. There are several hyposignal (compared with muscle) nodular thickenings, 3–3.5 cm in diameter, along deep division branches of the sciatic nerve (short black arrows), and infracentimetric nodular thickenings in subcutaneous nerve branches (long black arrows). B, C. The main trunk of the tibial nerve exhibits diffuse iso/hyposignal thickening (with some focal size variations) along its course in the lower leg and ankle (white arrowheads), and nerve fascicles appear to be dissected by infiltrative tissue extending to nearby adipose and muscle tissues (indicated by x). A, C: axial views; B: coronal view.
330
revue neurologique 172 (2016) 324–334
(motor nerve conduction study results: proximal amplitude reduction of 77%, focal nerve conduction reduced to 16 m/s; tibialis anterior and extensor digitorum longus electromyography results: absence of abnormal insertional and spontaneous activity, reduced MUAP recruitment with no morphological changes). A sural nerve conduction study and electromyography of the medial gastrocnemius muscle were normal. Magnetic resonance imaging (MRI) revealed plexiform neurofibroma-like lesions (Fig. 1). Nodular thickenings of various sizes were found in the popliteal region, along the tibial and fibular divisions of the right sciatic nerve, and along the superficial subcutaneous nerves. More distally, the main trunk of the tibial nerve was diffusely enlarged, and numerous subcutaneous nerves were also focally thickened. The nerves appeared intact, yet were dissected by partially enhancing infiltrative tissue, which extended along the nearby vascular structures, and adipose and muscle tissues. After further questioning, the patient admitted to a 6-month history of severe weight loss and profuse night sweats. Multiple painless cervical, axillary and inguinal lymph nodes were found on examination. Laboratory tests showed mild anemia, a raised erythrocyte sedimentation rate and raised serum lactate dehydrogenase levels. Whole-body 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) revealed intense FDG uptake along the right sciatic nerve as well as at numerous nodal and extranodal sites. Open biopsy of an easily accessible right inguinal hypermetabolic lymph node was performed and revealed an aggressive B-cell non-Hodgkin’s lymphoma, which was intermediate between diffuse large B-cell lymphoma and Burkitt’s lymphoma. R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy was administered, prompting an initial complete response as assessed by whole-body 18-FDG PET/CT. Unfortunately, a relapse occurred a month after the last course of chemotherapy. Neurolymphomatosis (NL), defined as infiltration of the peripheral nervous system by malignant lymphocytes, is a rare disorder that differs from those commonly associated with leukemia or lymphoma and arises as a result of irradiation or chemotherapy, or as a paraneoplastic effect [1]. In a small proportion of patients, NL may be the first manifestation of disease. In such patients, the diagnosis of NL may be particularly challenging and yet is of crucial importance as it enables appropriate treatment at an early stage of disease. MRI is a highly useful diagnostic tool in NL, having a sensitivity of almost 80% [1]. Roots, plexuses and nerves infiltrated by malignant lymphocytes are enlarged and commonly enhanced on gadolinium administration. In cases of solitary nerve involvement, two patterns have so far been described: localized nerve thickening (pattern 1); and diffuse linear thickening of the main nerve trunk (pattern 2). The present report is of a plexiform pattern (multinodular thickenings of deep and subcutaneous nerves), which differs from any previously reported patterns, and is thus expanding the spectrum of NL radiological presentations and broadening the differential diagnosis of plexiform lesions, which includes neurofibroma, schwannoma, nerve sheath myxoma, perineurioma, fibrohistiocytic tumor, malignant peripheral nerve sheath tumor, spindle cell lipoma, spindle cell nevus and tufted angioma [2–5].
Disclosure of interest The authors declare that they have no competing interest.
Acknowledgement We wish to thank Olivier Beuscart for his help in the preparation of the figures.
references
[1] Grisariu S, Avni B, Batchelor BM, van den Bent MJ, Bokstein F, Schiff D, et al. Neurolymphomatosis: an International Primary CNS Lymphoma Collaborative Group report. Blood 2010;115(24):5005–11. [2] Nishida Y, Tsukushi S, Urakawa H, Arai E, Kozawa E, Ishiguro N. Lower leg compartment syndrome in neurofibromatosis 1 patient with plexiform neurofibrom: a case report aneurysm rupture. Ann Vasc Surg 2014;28(4):1035. [3] Ko JY, Kim JE, Kim YH, Ro YS. Cutaneous plexiform schwannomas in a patient with neurofibromatosis type 2. Ann Dermatol 2009;21(4):402–5. [4] Zelger B, Weinlich G, Steiner H, Zelger BG, Egarter-Vigl E. Dermal and subcutaneous variants of plexiform fibrohistiocytic tumor. Am J Surg Pathol 1997;21(2):235–41. [5] Mentzel T, Kutzner H. Reticular and plexiform perineurioma: clinicopathological and immunohistochemical analysis of two cases and review of perineurial neoplasm of skin and soft tissues. Virchows Arch 2005;447(4):677–82.
R. Denaysa,* V. Baudrezb P. Abouhamadc T. Dere`mec G. Milbouwd J.-P. Hermannee a Department of Neurology, CHR Sambre & Meuse, avenue Albert Ier 185, 5000 Namur, Belgium b Department of Radiology, CHR Sambre & Meuse, avenue Albert Ier 185, 5000 Namur, Belgium c Department of Nuclear Medicine, CHR Sambre & Meuse, avenue Albert Ier 185, 5000 Namur, Belgium d Department of Neurosurgery, CHR Sambre & Meuse, avenue Albert Ier 185, 5000 Namur, Belgium e Department of Hemato-Oncology, CHR Sambre & Meuse, avenue Albert Ier 185, 5000 Namur, Belgium *Corresponding author. E-mail address: [email protected] (R. Denays) Received 9 December 2015 Accepted 18 February 2016 Available online 23 April 2016 http://dx.doi.org/10.1016/j.neurol.2016.02.008 0035-3787/# 2016 Elsevier Masson SAS. All rights reserved.