J Neurol (1992) 239 : 132-134
Journal of
Neurology © Springer-Verlag1992
Lymphoma-induced polyradiculopathy in AIDS: two cases Jean-Marc L~ger 1, Dominique H~nin 2, Laurent B~lec 1, Bertrand Mercier 1, Laurent Cohen 1, Pierre Bouche 1, Jean-Jacques Hauw 2, and Pascal Brunet 1 1Clinique des Maladies du Syst~me Nerveux and 2Laboratoire R. Escourolle, H6pital de la Salp~tri6re, 47, Boulevard de 1'H6pital, F-75651 Paris Cedex 13, France Received February 7, 1991 / Received in revised form May 27, 1991 / Accepted June 6, 1991
Summary. Progressive polyradiculopathy is a rare, welldocumented complication of the acquired immunodeficiency syndrome in man. It has been commonly attributed to a cytomegalovirus (CMV) infection. We report two HIV-infected patients with clinical and electrophysiological features of a unique, subacute, progressive polyradiculopathy. Post-mortem examination in case 1 disclosed an infiltration of the leptomeninges, the lumbar spinal cord, and the anterior and posterior roots by a B-cell immunoblastic lymphoma. Immunochemistry for H I V 1 and C M V was negative in the peripheral and the central nervous system. Case 2 showed bone-marrow involvement by a Burkitt type lymphoma. Specific chemotherapy was followed by both clinical improvement of the polyradiculopathy and complete remission on a second bone-marrow biopsy. These findings may indicate that a lymphoma must also be considered a possible cause of polyradiculopathy in A I D S .
Key words: A I D S - L y m p h o m a - Polyradiculopathy
Introduction The spectrum of peripheral nervous system complications occurring during the course of HIV1 infection mainly includes inflammatory demyelinating polyneuropathy, m o n o n e u r o p a t h y multiplex and distal predominantly sensory polyneuropathy [3, 5, 9, 12, 18]. Progressive polyradiculopathy in terminal A I D S was firstly reported by Moskowitz et al. [16], then by other authors [1, 2, 6, 7, 14, 17]. This complication seems to be rare and has been commonly attributed to a cytomegalovirus (CMV) infection. Recently, Miller et al. [15] published seven further cases with characteristic features of polyradiculopathy and evidence of cytomegalic inclusions at post-mortem examination in five cases. Nevertheless, several other treatable causes of progressive polyradiculopathy in individuals infected with HIV1 have been reOffprint requests to: J.-M. L6ger
ported, including syphilis [10, 11] and mycobacterial infection [19]. We report two cases in which a polyradiculopathy was the predominant manifestation of a lymphoma which occurred in the course of HIV1 infection.
Case reports Case 1
A 32-year-old homosexual man developed a right complete oculomotor palsy associated which cephalalgia, fever and lymphadenopathy. Brain CT and MRI were normal. The cerebrospinal fluid (CSF) contained 22 leucocytes/mm3, of which 84% were polymorphs. CSF protein was 52 mg/100 ml. Viral, bacterial and fungal cultures were negative. Enzyme-linked immunosorbent assay and Western blot for antibody to HIV1 were positive. The total lymphocyte count was 1705/mm3. Serum titres were 1/320 for CMV. Right carotid and vertebral angiography was normal. The neurological symptoms improved spontaneously in 1 month. Three months later he complained of nerve root pain and weakness in the right leg, which were followed by lumbar pain, cephalalgia, vomiting, fever and paraesthesia in both distal limbs. He also noticed a recurrence of the diplopia. Examination showed generalized lymphadenopathy, monoplegia with areflexia in the right leg, diminution of the vibration, joint position and pinprick sensation in both distal lower limbs. Plantar responses were absent. There was no bladder incontinence. There were a right abducens paresis. Mental status was normal. Brain CT was normal. A second CSF sample contained 220 leucocytes (95% lymphocytes)/ mm3 and 180mg/100ml protein; gamma globulin was 21% and IgG 320 rag/l; titres for CMV were 1/128. The serum total lymphocyte count was 2800 cells/ram3 (448 CD4); titres for CMV were 1/ 10000; VDRL and TPHA were negative. Tests were negative for hepatitis B surface antigen and cryptococcal antigen. Bacterial, fungal mycobacterial cultures were negative. Electrophysiological study showed a neurogenic pattern in the lower limbs. Motor conduction nerve velocities (MNCV) were as follows: right peroneal nerve, 40m/s [distal motor latency (DL), 4.8ms]; left peroneal nerve, 45m/s (DL: 5.1ms); right median nerve, 52m/s (DL: 3.3 ms). Sensory nerve conduction nerve velocities (SNCV) were: right sural nerve, 40 m/s (amplitude, 4 gV); left sural nerve, 42 m/s (amplitude, 5 gV); right median nerve, 46 m/s (amplitude, 30gV). During the following 3 months the patient was treated with prednisone, which led to be a mild improvement of the cephalalgia and the oculomotor signs, but the deficit extended to acom-
133
Case 2
Fig. 1A-C. Post-mortem examination in case 1. Lumbar spinal cord (L5): horizontal section, paraffin embedded. A Lymphoma cells invading the leptomeninges, the grey and white matter along the virchow-Robin spaces. H & E, × 22. B Infiltration of the posterior roots by the lymphoma. H & E, × 28. C Non-Hodgkin's lymphoma, immunoblastic type, in the leptomeninges (H & E, × I000
plete flaccid paraplegia with bowel and bladder incontinence. He developed diffuse pneumonia and died in respiratory failure. On post-mortem examination, the heart weighed 370 g. A necrotic, heterogeneous and sclerotic lesion (4 × 3 cm) was noticed on the right side, next to the right coronary artery. On microscopic examination, a non-Hodgkin's lymphoma, immunoblastic type, labelled by B-cells markers (L26, Dako) had invaded the pericardium and the myocardium. Bone marrow, spleen and liver were normal. The brain weighed 1530 g. The corpus callosum was enlarged, the ventricles, were collapsed and the ventricular walls were irregular and softened. On microscopic examination, the lymphoma infiltrated the leptomeniges, the corpus callosum, the ventricular walls and the adjacent grey and white matter, the cerebellum and the pons near the fourth ventricle. The lumbar spinal cord was invaded from the leptomeninges (Fig. 1A, C). Anterior and posterior roots, including cauda equina, were infiltrated as well (Fig. 1B). Thoracic and cervical parts of the spinal cord were spared. No HIV or CMV antigens were found in the central nervous system or in the spinal ganglia by immunohistochemistry on paraffin (HIV: p24, gp41, Dupont; CMV: M757, Dako), nor frozen (HIVI: p25, Genetic System; CMV: e13, Biosoft) sections.
A 47-year-old Caucasian bisexual man presented in 1986 with oral candidiasis which led to the diagnosis of HIV1 infection. In July 1988, he developed pleural tuberculosis which improved under specific treatment. H e was additionally treated by zidovudine i g/ day from January 1988. In May 1989 he complained of lumbar pain, nerve root pain affecting the thighs, buttocks and inguinal areas, proximal weakness and paraesthesias of the feet, which slowly worsened for 3 months. Zidovudine had been stopped 2 months before because of the possibility of muscular side-effects of this drug, but this interruption did not change the symptoms. Asthenia and fever were present. The patient noticed dysuria but was continent of faeces. Neurological examination showed a symmetrical bilateral motor defect affecting the iliopsoas and the quadriceps femoris. The ankle jerks were absent. Vibration, joint position and pinprick sensation were diminished in both distal lower limbs. The upper extremities were normal, including reflexes and muscle strength. The cranial nerves were normal including fimdi, pupils and auditory acuity. Mental status was normal. General examination showed hepatomegaly, splenomegaly and generalized lymphadenopathy which were known since 1986 and bad remained unchanged. Brain CT and MRI were normal. A lumbar myeloradiculography was normal. CSF contained 20 leucocytes/mm3, of which 86% were lymphocytes and 10% mononuclear cells. CSF protein was 89 mg/100ml and glucose was 2.7mmol/1, No abnormal cells were found; gamma globulin was 42% with three oligoclonal bands in the gamma zone, and IgG 320 mg/1; VDRL was negative. The serum total lymphocyte count was 1134/mm 3 (T4:79 celts/ram3; T8:567 cells/ram3; T4/TS: 0.14). Serum VDRL and TPHA were negative. Serum titres for CMV were 1/5120. Cryptococcal antigen, cultures for bacteria, fungus and mycobacteria, and viruses including herpes simplex virus and CMV were all negative. Electrophysiological study revealed a neurogenic pattern (reduced interference pattern at full voluntary contraction) in both quadriceps femoris and the right tibialis anterior. MNCV were slightly reduced in the lower limbs (right peroneal nerve, 37.2 m/s; left peroneal nerve, 37.1m/s) with normal distal motor latencies and normal amplitude of the muscle action potentials. MNCV were normal in the upper limbs. SNCV were normal in all four limbs. Bone-marrow examination showed numerous lymphomatous Burkitt-like cells (66%), confirming bone-marrow involvement with a diffuse lymphoid infiltration composed of small cells with non-cleaved nuclei resembling lymphomatous Burkitt-like cells and rare larger lymphoid, cells with plasmoblastic differention. The patient was treated with Adriamycin, bleomycin, cyclophosphamide and methylprednisolone, associated with intrathecal therapy (methotrexate, cytarabine, methylprednisolone), which led to a dramatic improvement of the polyradiculopathy: the strength returned to normal in the lower limbs and the root pain and paraesthesias improved. A second bone marrow biopsy performed 1 month later was normal. Two months later he was admitted to another hospital, where he died from respiratory failure. No postmortem examination was performed.
Discussion O u r two p a t i e n t s h a d clinical a n d l a b o r a t o r y f e a t u r e s of a unique progressive AIDS-related polyradiculopathy, similar to t h o s e p r e v i o u s l y r e p o r t e d in t h e l i t e r a t u r e [1, 2, 6, 7, 14-17]. T h e clinical findings are: l u m b a r p a i n , n e r v e r o o t p a i n , e x t e n s i v e m o t o r a n d s e n s o r y defects a n d t e n d o n a r e f l e x i a in t h e l o w e r l i m b s , w h i c h e a r l y a n d severe sphincter dysfunction. Encephalitis and involvem e n t of c r a n i a l n e r v e s , as in o u r case 1, a r e a s s o c i a t e d in s o m e cases [2, 14, 16]. M y e l o g r a p h y is n o r m a l . C S F is strikingly a b n o r m a l , s h o w i n g a p o l y m o r p h o n u c l e a r p l e o -
134 cytosis and a m a r k e d elevation of protein content. Electrophysiological studies disclose a widespread acute partial denervation with normal nerve conduction velocities. These patients have an acute course leading to a rapidly progressive flaccid paraplegia and death in a few weeks or months. These features are of a well-characterized peripheral neuropathy which is quite different f r o m both inflammatory demyelinating polyneuropathy mainly reported in early H I V 1 infection [3, 12] and from painful sensory polyneuropathy which also occurs in terminal A I D S [4]. This polyradiculopathy has been attributed to a C M V infection in the majority of the published cases based on clinical, serological and neuropathological findings. C M V retinitis is associated with the polyradiculopathy in some cases [1, 15]; C M V was cultured f r o m CSF in four of the seven patients reported by Miller et al. [15]; p o s t - m o r t e m examination disclosed an inflammatory polyradiculopathy with characteristic cytomegalic inclusions in the case reported by Mahieux et al. [14], Chimelli et al. [2] and in five of the seven cases of Miller et al. [15]. In addition, two of the patients reported by Miller et al. [15] improved under treatment with ganciclovir. Several other treatable causes of polyradiculopathy in individuals infected with H I V include syphilis, which improves with penicillin therapy [10, 11], and mycobacteria [19]. In our cases syphilitic serology, bacterial and fungal cultures in the CSF were negative, but titres for C M V were high in the serum despite the lack of clinical manifestations. Nevertheless neuropathological examination in case 1 failed to find C M V inclusions in the spinal cord and intra-dural lower spinal roots. In addition, immunochemistry for H I V 1 and C M V was negative in the peripheral nerves, the spinal ganglia, the dorsal roots, the spinal cord and the central nervous system. On the other hand, p o s t - m o r t e m examination in case 1 revealed infiltration of the leptomeninges, the lumbar spinal cord, and the anterior and posterior roots by a B-cell immunoblastic l y m p h o m a . Case 2 had bone m a r r o w involvement by a Burkitt-type l y m p h o m a , and specific c h e m o t h e r a p y led both to clinical i m p r o v e m e n t and complete remission on the second m a r r o w biopsy. Pathological cases of spinal root infiltration by a non-Hodgkin's l y m p h o m a have been reported by others [7, 8]. Thus, we postulate that the polyradiculopathy was related to the l y m p h o m a in both cases. The clinical and laboratory features were not different f r o m those of C M V polyradiculopathy, except in two points: the course was m o r e progressive and relapsing in case 1; the CSF examination in our two cases showed a lymphocytic pleocytosis in contrast to the polym o r p h o n u c l e a r pleocytosis predominating in the cases reported by Miller et al. [15]. These findings m a y indicate that a l y m p h o m a must also be considered a possible cause of polyradiculopathy in A I D S .
References 1. Behar R, Wiley C, McCutchan JA (1987) Cytomegalovirus polyradiculoneuropathy in acquired immune deficiency syndrome. Neurology 37 : 557-561 2. Chimelli L, Freitas MRG de, Bazin AR, Mhiri C, Scaravilli F, Gray F (1990) Enc6phalo-my6lo-radiculite ~ cytom6galovirus au cours du syndrome d'immuno-d6ficience acquise. Rev Neurol (Paris) 146 : 354-360 3. Cornblath DR, McArthur JC, Kennedy PGE, Witte AS, Griffin JW (1987) Inflammatory demyelinating peripheral neuropathies associated with human T-cell lymphotropic virus type III infection. Ann Neurol 21:32-40 4. Cornblath DR, McArthur JC (1988) Predominantly sensory neuropathy in patients with AIDS and AIDS-related complex. Neurology 38 : 794-796 5. De La Monte SM, Gabuzda DH, Ho DH, Brown RH, Medley-White ET, Schooley RT, Hirsch MS, Bhan AK (1988) Peripheral neuropathy in the acquired immunodeficiency syndrome. Ann Neurol 23 : 485-492 6. Eidelberg D, Sotrel A, Vogel H, Walker P, Kleefield J, Crumpacker SD III (1986) Progressive polyradiculopathy in acquired immune deficiency syndrome. Neurology 36: 912-916 7. Gray F, Ghdrardi R (1990) Les ldsions m6dullaires et radiculaires au cours de l'infection par le virus de l'immunod6ficience humaine. Rev Neurol (Paris) 146 : 655-664 8. Hfinin D, Hauw JJ (1989) The neuropathology of AIDS. In: McKendall RR (ed) Handbook of clinical neurology, vol 12(56) Elsevier, Amsterdam, pp 507-524 9. Lange D J, Britton CB, Younger DS, Hays AP (1988) The neuromuscular manifestations of human immunodeficiency virus infection. Arch Neurol 45 : 1084-1088 10. Lanska MJ, Lanska D J, Schmidley JW (1988) Syphilitic polyradicnlopathy in an HIV-positive man. Neurology 38:12971301 11. Lanska DJ, Lanska MJ (1989) Treatable causes of meningomyeloradiculitis in individuals infected with human immunodeficiency virus. Arch Neuro146: 722-723 12. L~ger J-M, Bouche P, Bolgert F, Chaunu MP, Rosenheim M, Cathala HP, Gentilini M, Hauw J-J, Brunet P (1989) The spectrum of polyneuropathies in patients infected with HIV. J Neurol Neusorg Psychiatry 52 : 1369-1374 13. L6ger J-M, H6nin D, B61ec L, Bolgert F, Cohen L, Bouche P, Hauw J-J, Brunet P (1990) Clinico-pathological findings in 2 cases of polyradicnlopathy and lymphoma in AIDS (abstract). J Neurol Sci 98 [Suppl] : 157 14. Mahieux F, Gray F, Fdnelon G, Gh6rardi R, Adams D, Guillard A, Poirier J (1989) Acute myeloradiculitis due to cytomegalovirus as the initial manifestation of AIDS. J Neurol Neurosorg Psychiatry 52: 270-274 15. Miller RG, Storey JR, Greco CM (1990) Ganciclovir in the treatment of progressive AIDS-related polyradiculopathy. Neurology 40 : 569-574 16. Moskowitz LB, Gregorios JB, Hensley GT, Berger JR (1984) Cytomegalovirus induced demyelination associated with acquired immune deficiency syndrome. Arch Pathol Lab Med 108 : 873-877 17. Singh BM, Levine S, Yarrish RL, Hyland MJ, Jeanty D, Wormser GP (1986) Spinal cord syndromes in the acquired immune deficiency syndrome. Acta Neurol Scand 73 : 590-598 18. So YT, Holtzman DM, Abrams DI, Olney RK (1988) Peripheral neuropathy associated with acquired immunodeficiency syndrome. Arch Neurol 45 : 945-948 19. Woolsey RM, Chambers TJ, Chung HD, McGarry JD (1988) Mycobacterial meningomyelitis associated with human immunodeficiency virus infection. Arch Neurol 45 : 691-693
Journal of
Neurology © Springer-Verlag1992
Lymphoma-induced polyradiculopathy in AIDS: two cases Jean-Marc L~ger 1, Dominique H~nin 2, Laurent B~lec 1, Bertrand Mercier 1, Laurent Cohen 1, Pierre Bouche 1, Jean-Jacques Hauw 2, and Pascal Brunet 1 1Clinique des Maladies du Syst~me Nerveux and 2Laboratoire R. Escourolle, H6pital de la Salp~tri6re, 47, Boulevard de 1'H6pital, F-75651 Paris Cedex 13, France Received February 7, 1991 / Received in revised form May 27, 1991 / Accepted June 6, 1991
Summary. Progressive polyradiculopathy is a rare, welldocumented complication of the acquired immunodeficiency syndrome in man. It has been commonly attributed to a cytomegalovirus (CMV) infection. We report two HIV-infected patients with clinical and electrophysiological features of a unique, subacute, progressive polyradiculopathy. Post-mortem examination in case 1 disclosed an infiltration of the leptomeninges, the lumbar spinal cord, and the anterior and posterior roots by a B-cell immunoblastic lymphoma. Immunochemistry for H I V 1 and C M V was negative in the peripheral and the central nervous system. Case 2 showed bone-marrow involvement by a Burkitt type lymphoma. Specific chemotherapy was followed by both clinical improvement of the polyradiculopathy and complete remission on a second bone-marrow biopsy. These findings may indicate that a lymphoma must also be considered a possible cause of polyradiculopathy in A I D S .
Key words: A I D S - L y m p h o m a - Polyradiculopathy
Introduction The spectrum of peripheral nervous system complications occurring during the course of HIV1 infection mainly includes inflammatory demyelinating polyneuropathy, m o n o n e u r o p a t h y multiplex and distal predominantly sensory polyneuropathy [3, 5, 9, 12, 18]. Progressive polyradiculopathy in terminal A I D S was firstly reported by Moskowitz et al. [16], then by other authors [1, 2, 6, 7, 14, 17]. This complication seems to be rare and has been commonly attributed to a cytomegalovirus (CMV) infection. Recently, Miller et al. [15] published seven further cases with characteristic features of polyradiculopathy and evidence of cytomegalic inclusions at post-mortem examination in five cases. Nevertheless, several other treatable causes of progressive polyradiculopathy in individuals infected with HIV1 have been reOffprint requests to: J.-M. L6ger
ported, including syphilis [10, 11] and mycobacterial infection [19]. We report two cases in which a polyradiculopathy was the predominant manifestation of a lymphoma which occurred in the course of HIV1 infection.
Case reports Case 1
A 32-year-old homosexual man developed a right complete oculomotor palsy associated which cephalalgia, fever and lymphadenopathy. Brain CT and MRI were normal. The cerebrospinal fluid (CSF) contained 22 leucocytes/mm3, of which 84% were polymorphs. CSF protein was 52 mg/100 ml. Viral, bacterial and fungal cultures were negative. Enzyme-linked immunosorbent assay and Western blot for antibody to HIV1 were positive. The total lymphocyte count was 1705/mm3. Serum titres were 1/320 for CMV. Right carotid and vertebral angiography was normal. The neurological symptoms improved spontaneously in 1 month. Three months later he complained of nerve root pain and weakness in the right leg, which were followed by lumbar pain, cephalalgia, vomiting, fever and paraesthesia in both distal limbs. He also noticed a recurrence of the diplopia. Examination showed generalized lymphadenopathy, monoplegia with areflexia in the right leg, diminution of the vibration, joint position and pinprick sensation in both distal lower limbs. Plantar responses were absent. There was no bladder incontinence. There were a right abducens paresis. Mental status was normal. Brain CT was normal. A second CSF sample contained 220 leucocytes (95% lymphocytes)/ mm3 and 180mg/100ml protein; gamma globulin was 21% and IgG 320 rag/l; titres for CMV were 1/128. The serum total lymphocyte count was 2800 cells/ram3 (448 CD4); titres for CMV were 1/ 10000; VDRL and TPHA were negative. Tests were negative for hepatitis B surface antigen and cryptococcal antigen. Bacterial, fungal mycobacterial cultures were negative. Electrophysiological study showed a neurogenic pattern in the lower limbs. Motor conduction nerve velocities (MNCV) were as follows: right peroneal nerve, 40m/s [distal motor latency (DL), 4.8ms]; left peroneal nerve, 45m/s (DL: 5.1ms); right median nerve, 52m/s (DL: 3.3 ms). Sensory nerve conduction nerve velocities (SNCV) were: right sural nerve, 40 m/s (amplitude, 4 gV); left sural nerve, 42 m/s (amplitude, 5 gV); right median nerve, 46 m/s (amplitude, 30gV). During the following 3 months the patient was treated with prednisone, which led to be a mild improvement of the cephalalgia and the oculomotor signs, but the deficit extended to acom-
133
Case 2
Fig. 1A-C. Post-mortem examination in case 1. Lumbar spinal cord (L5): horizontal section, paraffin embedded. A Lymphoma cells invading the leptomeninges, the grey and white matter along the virchow-Robin spaces. H & E, × 22. B Infiltration of the posterior roots by the lymphoma. H & E, × 28. C Non-Hodgkin's lymphoma, immunoblastic type, in the leptomeninges (H & E, × I000
plete flaccid paraplegia with bowel and bladder incontinence. He developed diffuse pneumonia and died in respiratory failure. On post-mortem examination, the heart weighed 370 g. A necrotic, heterogeneous and sclerotic lesion (4 × 3 cm) was noticed on the right side, next to the right coronary artery. On microscopic examination, a non-Hodgkin's lymphoma, immunoblastic type, labelled by B-cells markers (L26, Dako) had invaded the pericardium and the myocardium. Bone marrow, spleen and liver were normal. The brain weighed 1530 g. The corpus callosum was enlarged, the ventricles, were collapsed and the ventricular walls were irregular and softened. On microscopic examination, the lymphoma infiltrated the leptomeniges, the corpus callosum, the ventricular walls and the adjacent grey and white matter, the cerebellum and the pons near the fourth ventricle. The lumbar spinal cord was invaded from the leptomeninges (Fig. 1A, C). Anterior and posterior roots, including cauda equina, were infiltrated as well (Fig. 1B). Thoracic and cervical parts of the spinal cord were spared. No HIV or CMV antigens were found in the central nervous system or in the spinal ganglia by immunohistochemistry on paraffin (HIV: p24, gp41, Dupont; CMV: M757, Dako), nor frozen (HIVI: p25, Genetic System; CMV: e13, Biosoft) sections.
A 47-year-old Caucasian bisexual man presented in 1986 with oral candidiasis which led to the diagnosis of HIV1 infection. In July 1988, he developed pleural tuberculosis which improved under specific treatment. H e was additionally treated by zidovudine i g/ day from January 1988. In May 1989 he complained of lumbar pain, nerve root pain affecting the thighs, buttocks and inguinal areas, proximal weakness and paraesthesias of the feet, which slowly worsened for 3 months. Zidovudine had been stopped 2 months before because of the possibility of muscular side-effects of this drug, but this interruption did not change the symptoms. Asthenia and fever were present. The patient noticed dysuria but was continent of faeces. Neurological examination showed a symmetrical bilateral motor defect affecting the iliopsoas and the quadriceps femoris. The ankle jerks were absent. Vibration, joint position and pinprick sensation were diminished in both distal lower limbs. The upper extremities were normal, including reflexes and muscle strength. The cranial nerves were normal including fimdi, pupils and auditory acuity. Mental status was normal. General examination showed hepatomegaly, splenomegaly and generalized lymphadenopathy which were known since 1986 and bad remained unchanged. Brain CT and MRI were normal. A lumbar myeloradiculography was normal. CSF contained 20 leucocytes/mm3, of which 86% were lymphocytes and 10% mononuclear cells. CSF protein was 89 mg/100ml and glucose was 2.7mmol/1, No abnormal cells were found; gamma globulin was 42% with three oligoclonal bands in the gamma zone, and IgG 320 mg/1; VDRL was negative. The serum total lymphocyte count was 1134/mm 3 (T4:79 celts/ram3; T8:567 cells/ram3; T4/TS: 0.14). Serum VDRL and TPHA were negative. Serum titres for CMV were 1/5120. Cryptococcal antigen, cultures for bacteria, fungus and mycobacteria, and viruses including herpes simplex virus and CMV were all negative. Electrophysiological study revealed a neurogenic pattern (reduced interference pattern at full voluntary contraction) in both quadriceps femoris and the right tibialis anterior. MNCV were slightly reduced in the lower limbs (right peroneal nerve, 37.2 m/s; left peroneal nerve, 37.1m/s) with normal distal motor latencies and normal amplitude of the muscle action potentials. MNCV were normal in the upper limbs. SNCV were normal in all four limbs. Bone-marrow examination showed numerous lymphomatous Burkitt-like cells (66%), confirming bone-marrow involvement with a diffuse lymphoid infiltration composed of small cells with non-cleaved nuclei resembling lymphomatous Burkitt-like cells and rare larger lymphoid, cells with plasmoblastic differention. The patient was treated with Adriamycin, bleomycin, cyclophosphamide and methylprednisolone, associated with intrathecal therapy (methotrexate, cytarabine, methylprednisolone), which led to a dramatic improvement of the polyradiculopathy: the strength returned to normal in the lower limbs and the root pain and paraesthesias improved. A second bone marrow biopsy performed 1 month later was normal. Two months later he was admitted to another hospital, where he died from respiratory failure. No postmortem examination was performed.
Discussion O u r two p a t i e n t s h a d clinical a n d l a b o r a t o r y f e a t u r e s of a unique progressive AIDS-related polyradiculopathy, similar to t h o s e p r e v i o u s l y r e p o r t e d in t h e l i t e r a t u r e [1, 2, 6, 7, 14-17]. T h e clinical findings are: l u m b a r p a i n , n e r v e r o o t p a i n , e x t e n s i v e m o t o r a n d s e n s o r y defects a n d t e n d o n a r e f l e x i a in t h e l o w e r l i m b s , w h i c h e a r l y a n d severe sphincter dysfunction. Encephalitis and involvem e n t of c r a n i a l n e r v e s , as in o u r case 1, a r e a s s o c i a t e d in s o m e cases [2, 14, 16]. M y e l o g r a p h y is n o r m a l . C S F is strikingly a b n o r m a l , s h o w i n g a p o l y m o r p h o n u c l e a r p l e o -
134 cytosis and a m a r k e d elevation of protein content. Electrophysiological studies disclose a widespread acute partial denervation with normal nerve conduction velocities. These patients have an acute course leading to a rapidly progressive flaccid paraplegia and death in a few weeks or months. These features are of a well-characterized peripheral neuropathy which is quite different f r o m both inflammatory demyelinating polyneuropathy mainly reported in early H I V 1 infection [3, 12] and from painful sensory polyneuropathy which also occurs in terminal A I D S [4]. This polyradiculopathy has been attributed to a C M V infection in the majority of the published cases based on clinical, serological and neuropathological findings. C M V retinitis is associated with the polyradiculopathy in some cases [1, 15]; C M V was cultured f r o m CSF in four of the seven patients reported by Miller et al. [15]; p o s t - m o r t e m examination disclosed an inflammatory polyradiculopathy with characteristic cytomegalic inclusions in the case reported by Mahieux et al. [14], Chimelli et al. [2] and in five of the seven cases of Miller et al. [15]. In addition, two of the patients reported by Miller et al. [15] improved under treatment with ganciclovir. Several other treatable causes of polyradiculopathy in individuals infected with H I V include syphilis, which improves with penicillin therapy [10, 11], and mycobacteria [19]. In our cases syphilitic serology, bacterial and fungal cultures in the CSF were negative, but titres for C M V were high in the serum despite the lack of clinical manifestations. Nevertheless neuropathological examination in case 1 failed to find C M V inclusions in the spinal cord and intra-dural lower spinal roots. In addition, immunochemistry for H I V 1 and C M V was negative in the peripheral nerves, the spinal ganglia, the dorsal roots, the spinal cord and the central nervous system. On the other hand, p o s t - m o r t e m examination in case 1 revealed infiltration of the leptomeninges, the lumbar spinal cord, and the anterior and posterior roots by a B-cell immunoblastic l y m p h o m a . Case 2 had bone m a r r o w involvement by a Burkitt-type l y m p h o m a , and specific c h e m o t h e r a p y led both to clinical i m p r o v e m e n t and complete remission on the second m a r r o w biopsy. Pathological cases of spinal root infiltration by a non-Hodgkin's l y m p h o m a have been reported by others [7, 8]. Thus, we postulate that the polyradiculopathy was related to the l y m p h o m a in both cases. The clinical and laboratory features were not different f r o m those of C M V polyradiculopathy, except in two points: the course was m o r e progressive and relapsing in case 1; the CSF examination in our two cases showed a lymphocytic pleocytosis in contrast to the polym o r p h o n u c l e a r pleocytosis predominating in the cases reported by Miller et al. [15]. These findings m a y indicate that a l y m p h o m a must also be considered a possible cause of polyradiculopathy in A I D S .
References 1. Behar R, Wiley C, McCutchan JA (1987) Cytomegalovirus polyradiculoneuropathy in acquired immune deficiency syndrome. Neurology 37 : 557-561 2. Chimelli L, Freitas MRG de, Bazin AR, Mhiri C, Scaravilli F, Gray F (1990) Enc6phalo-my6lo-radiculite ~ cytom6galovirus au cours du syndrome d'immuno-d6ficience acquise. Rev Neurol (Paris) 146 : 354-360 3. Cornblath DR, McArthur JC, Kennedy PGE, Witte AS, Griffin JW (1987) Inflammatory demyelinating peripheral neuropathies associated with human T-cell lymphotropic virus type III infection. Ann Neurol 21:32-40 4. Cornblath DR, McArthur JC (1988) Predominantly sensory neuropathy in patients with AIDS and AIDS-related complex. Neurology 38 : 794-796 5. De La Monte SM, Gabuzda DH, Ho DH, Brown RH, Medley-White ET, Schooley RT, Hirsch MS, Bhan AK (1988) Peripheral neuropathy in the acquired immunodeficiency syndrome. Ann Neurol 23 : 485-492 6. Eidelberg D, Sotrel A, Vogel H, Walker P, Kleefield J, Crumpacker SD III (1986) Progressive polyradiculopathy in acquired immune deficiency syndrome. Neurology 36: 912-916 7. Gray F, Ghdrardi R (1990) Les ldsions m6dullaires et radiculaires au cours de l'infection par le virus de l'immunod6ficience humaine. Rev Neurol (Paris) 146 : 655-664 8. Hfinin D, Hauw JJ (1989) The neuropathology of AIDS. In: McKendall RR (ed) Handbook of clinical neurology, vol 12(56) Elsevier, Amsterdam, pp 507-524 9. Lange D J, Britton CB, Younger DS, Hays AP (1988) The neuromuscular manifestations of human immunodeficiency virus infection. Arch Neurol 45 : 1084-1088 10. Lanska MJ, Lanska D J, Schmidley JW (1988) Syphilitic polyradicnlopathy in an HIV-positive man. Neurology 38:12971301 11. Lanska DJ, Lanska MJ (1989) Treatable causes of meningomyeloradiculitis in individuals infected with human immunodeficiency virus. Arch Neuro146: 722-723 12. L~ger J-M, Bouche P, Bolgert F, Chaunu MP, Rosenheim M, Cathala HP, Gentilini M, Hauw J-J, Brunet P (1989) The spectrum of polyneuropathies in patients infected with HIV. J Neurol Neusorg Psychiatry 52 : 1369-1374 13. L6ger J-M, H6nin D, B61ec L, Bolgert F, Cohen L, Bouche P, Hauw J-J, Brunet P (1990) Clinico-pathological findings in 2 cases of polyradicnlopathy and lymphoma in AIDS (abstract). J Neurol Sci 98 [Suppl] : 157 14. Mahieux F, Gray F, Fdnelon G, Gh6rardi R, Adams D, Guillard A, Poirier J (1989) Acute myeloradiculitis due to cytomegalovirus as the initial manifestation of AIDS. J Neurol Neurosorg Psychiatry 52: 270-274 15. Miller RG, Storey JR, Greco CM (1990) Ganciclovir in the treatment of progressive AIDS-related polyradiculopathy. Neurology 40 : 569-574 16. Moskowitz LB, Gregorios JB, Hensley GT, Berger JR (1984) Cytomegalovirus induced demyelination associated with acquired immune deficiency syndrome. Arch Pathol Lab Med 108 : 873-877 17. Singh BM, Levine S, Yarrish RL, Hyland MJ, Jeanty D, Wormser GP (1986) Spinal cord syndromes in the acquired immune deficiency syndrome. Acta Neurol Scand 73 : 590-598 18. So YT, Holtzman DM, Abrams DI, Olney RK (1988) Peripheral neuropathy associated with acquired immunodeficiency syndrome. Arch Neurol 45 : 945-948 19. Woolsey RM, Chambers TJ, Chung HD, McGarry JD (1988) Mycobacterial meningomyelitis associated with human immunodeficiency virus infection. Arch Neurol 45 : 691-693
