- Email: [email protected]
Minimal Change Nephrotic Syndrome With Stiff-Person Syndrome: Is There a Link?
CASE REPORT
Minimal Change Nephrotic Syndrome With Stiff-Person Syndrome: Is There a Link? Ihsan Ergün, MD, M. Cenk Akbostanci, MD, Bas¸ol Canbakan, MD, Bilge Koçer, MD, Arzu Ensari, MD, Gökhan Nergizogˇlu, MD, and Kenan Keven, MD ● Stiff-person syndrome is a rare, likely immune-mediated neurological disorder characterized by painful spasms and progressive symmetric rigidity of the axial and proximal limb muscles. Rigidity of truncal muscles and continuous contraction of the agonist and antagonist muscles caused by involuntary motor-unit firing at rest are the hallmarks of stiff-person syndrome. Immunosuppressive therapy has induced remission in patients with stiff-person syndrome. We report a patient with stiff-person syndrome with minimal change nephrotic syndrome (MCNS). The pathophysiologic states of stiff-person syndrome and MCNS are unclear. T-Cell– dependent mechanisms are highly suspected for the pathogenesis of both. The diagnosis of stiff-person syndrome was made on the basis of clinical and laboratory findings, and both MCNS and stiff-person syndrome resolved completely with immunosuppressive therapy. To our knowledge, this is the first case of stiff-person syndrome in association with MCNS in the literature. Am J Kidney Dis 46:E11-E14. © 2005 by the National Kidney Foundation, Inc. INDEX WORDS: Minimal change disease; nephrotic syndrome; stiff-man syndrome; stiff-person syndrome.
S
TIFF-PERSON SYNDROME is a rare neurological disorder characterized by painful spasms and progressive symmetric rigidity of the axial and proximal limb muscles. Continuous contraction of the agonist and antagonist muscles caused by involuntary motor-unit firing at rest are the clinical and electrophysiological hallmarks of stiff-person syndrome. The diagnosis of stiff-person syndrome depends on clinical findings and the exclusion of other neurological disorders.1 Drugs that enhance ␥-aminobutyric acid neurotransmission are used for symptomatic treatment. Immunosuppressive therapy, including high doses of steroids, has resolved stiffperson syndrome. Although frequent associations between stiff-person syndrome and other autoimmune disorders, such as type 1 diabetes mellitus, thyroiditis, myasthenia gravis, pernicious anemia, and vitiligo, previously have been described,2,3 to the best of our knowledge, this is the first case of stiff-person syndrome in association with minimal change nephrotic syndrome (MCNS) for which T-cell–dependent mechanisms are highly suspected in the pathogenesis for both. CASE REPORT A 30-year-old man was referred to the hospital for investigation of recent painful spasms and stiffness in his back and proximal extremity muscles. He had felt painful spasms and muscular rigidity on his left shoulder and leg for 2 months. The rigidity was characterized by episodic painful spasms and stiffness. While the stiffness had been spreading to other areas of the body, including the trunk, peripheral edema
developed. He had difficulty walking and bending. He was not able to perform his routine daily activities. On admission, blood pressure was 100/70 mm Hg, and physical examination showed 2⫹⫹ pretibial pitting edema. During neurological examination, he had spasms superimposed on rigidity on his trunk and limbs. His gait was slow. His sensorial examination findings and muscle strength were normal. Deep-tendon reflexes were brisk. There was no evidence of myotonia or extrapyramidal or pyramidal dysfunction. During the examination, painful contraction of the trunk and limb muscles was noticed in both agonist and antagonist muscles. Electrophysiological study showed contractions of the agonist and antagonist muscles and continuous motor-unit activity in the lumbar paraspinal, rectus abdominis (Fig 1), bilateral anterior tibial, and gastrocnemius muscles at rest. Laboratory findings on admission were as follows: hemoglobin, 13.9 g/dL (139 g/L); total leukocyte count, 8,600/ L; serum creatinine, 0.7 mg/dL (62 mol/L); sedimentation rate, 17 mm/h; and C-reactive protein, 3.54 mg/L (normal range, 0 to 5 mg/L). He had proteinuria (protein, 8.9 g/d), hypoalbuminemia (albumin, 2.4 g/dL [24 g/L]), and hyperlipidemia (total cholesterol, 287 mg/dL [7.42 mmol/
From the Departments of Nephrology, Neurology, and Pathology, Ankara University School of Medicine, Ibni Sina Hospital, Ankara, Turkey. Received December 22, 2004; accepted in revised form March 14, 2005. Originally published online as doi:10.1053/j.ajkd.2005.03.009 on May 18, 2005. Address reprint requests to Ihsan Ergün, MD, Department of Nephrology, Ankara University School of Medicine, Ibni Sina Hospital, Sihhiye, 06100, Ankara, Turkey. E-mail: [email protected] or [email protected] © 2005 by the National Kidney Foundation, Inc. 0272-6386/05/4601-0031$30.00/0 doi:10.1053/j.ajkd.2005.03.009
American Journal of Kidney Diseases, Vol 46, No 1 (July), 2005: E11-E14
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Fig 1. Electromyographic activity of the patient at rest. Spontaneous spasms in the right lumbar paraspinal and rectus abdominis muscles.
L]; triglyceride, 274 mg/dL [3.09 mmol/L]). Urine microscopic examination showed no erythrocytes or casts. Serum lactate dehydrogenase (142 U/L) and creatine phosphokinase (32 U/L) levels were normal. Test results for antinuclear antibody, antineutrophil cytoplasmic antibody, hepatitis B virus surface antigen, hepatitis C virus antibody, and human immunodeficiency virus antibody were negative. Other biochemical parameters, complement levels (C3c and C4), and cerebrospinal fluid were normal. Immune electrophoresis showed no evidence of a paraprotein. A renal biopsy was performed for nephrotic syndrome. Evaluation of light microscopy was normal, with negative immunofluorescence findings, and electron microscopy showed diffuse foot-process fusion without electron-dense deposits, compatible with minimal change disease. The diagnosis of stiff-person syndrome was based on the patient’s history, neurological examination, and electrophysiological findings. To exclude a malignancy, a computed tomographic scan of the thorax, magnetic resonance image of the brain, ultrasonographic evaluation of the abdomen, gastroscopy, and colonoscopy were performed, and all showed normal results.
Fig 2. Electromyographic activity of the patient at rest. Return to normal.
After the diagnosis, diazepam, 10 mg/d, was administered, and neurological symptoms regressed partially. After documentation of MCNS, 3-day methylprednisolone (500 mg/d) pulse therapy was initiated, followed by oral prednisolone (1 mg/kg/d) with cyclophosphamide (2 mg/kg/d). Oral prednisolone therapy was continued for a month with the same dose, then tapered slowly to 0.3 mg/kg/d. Month 2, nephrotic syndrome remitted partially, and month 3, proteinuria completely disappeared. Control serum albumin level was 4 g/dL (40 g/L). After remission, the cyclophosphamide dose was tapered to 1 mg/kg/d. Oral prednisolone and cyclophosphamide therapy was continued for 6 months, then stopped. Neurological symptoms and findings completely disappeared after pulse therapy, with normalization of electromyographic findings (Fig 2). Diazepam therapy was discontinued after 6 months. No recurrence was noticed during 1 year after cessation of the therapy.
DISCUSSION
Stiff-person syndrome is a rare central nervous system disorder characterized by progres-
MCNS WITH STIFF-PERSON SYNDROME
sive stiffness of predominantly axial and proximal limb muscles. Diagnosis of this rare condition depends on the clinical findings of axial and proximal limb rigidity, painful spasms, and normal neurological findings, except for brisk deeptendon reflexes.1 Our patient had painful spasms and stiffness in his back and proximal muscles. His neurological examination findings were normal, except for brisk deep-tendon reflexes. For definitive diagnosis, it is important to show continuous muscle activity in the trunk and proximal limb muscles at rest. We performed electromyography, showing simultaneous motor-unit firing of the lumbar paraspinal and rectus abdominis muscles at rest. Dystonia and orthostatic tremor are the primary disorders that should be considered in the differential diagnosis of stiff-person syndrome. Patients may report pain and muscle cramping in both disorders, but the symptoms are seen especially when standing and during motion in dystonia. Tetanus, progressive encephalomyelitis with rigidity, and Isaacs sydrome are the rare conditions resembling stiff-person syndrome.4 The pathophysiological states of stiff-person syndrome and MCNS are unclear, but likely are immune mediated, and T cells have a key role in the pathogenesis of both. Patients with stiff-person syndrome have antibodies against glutamic acid decarboxylase (GAD), which catalyzes the conversion of glutamic acid to ␥-aminobutyric acid, the major inhibitory neurotransmitter in the central nervous system. Antibodies to GAD are detected in approximately 60% to 80% of patients with stiff-person syndrome, but also have been seen in neurological and non-neurological diseases without rigidity or spasm.5 Although anti-GAD antibodies are an excellent marker6 for stiff-person syndrome, we were not able to check anti-GAD antibodies in our patient. However, it should be considered that anti-GAD antibodies are neither essential for the diagnosis of stiff-person syndrome3 nor a follow-up marker for stiff-person syndrome.6 When the disease is active or in relapse, T-cell proliferation against GAD and cytokine release from antigen-stimulated T cells (interferon ␥) were determined.3 In patients with stiff-person syndrome, GADspecific cellular proliferation, the synthesis of cytoplasmic interleukin 4, and interferon ␥ levels
e13
produced by activated T cells were significantly greater than in healthy controls.7 Although antibody concentrations against GAD showed no correlation with neurological symptoms, increased T-cell reactivity has an evident correlation. High doses of steroids, despite having no effect on antibody titers, can induce remission in patients with stiff-person syndrome.3 Similarly, many observations suggest a link between MCNS and T lymphocytes. A complex immune dysfunction is present in patients with MCNS. Investigations focused on soluble factors produced by activated T cells that alter and increase glomerular permeability to protein. TCell–dependent type 2 cytokines are predominant and can directly or indirectly cause MCNS.8 Certain cytokines, such as tumor necrosis factor ␣, have been implicated as a possible pathogenic factor in the mechanism of renal injury in patients with nephrotic syndrome.9 A well-documented association with lymphoma, remission of MCNS with measles infection (viral-associated immunosuppression), overexpression of lymphokines (interleukins 4 and 13) in relapse, depression of recall responses to common antigens or delayed cutaneous hypersensitivity reactions, and response to immunosuppressive therapy support the role of T cells in the pathogenesis of MCNS.8,10 Drugs that enhance ␥-aminobutyric acid neurotransmission, such as diazepam, baclofen, clonazepam, valproic acid, and clonidine, have improved clinical symptoms.1,2 Immunosuppressive agents, plasmapheresis, and immunoglobulin therapy11 have been found to be an effective treatment. We treated this patient with prednisolone and cyclophosphamide. Although it was not conventional for MCNS, cyclophosphamide has been shown to increase the response to therapy in stiff-person syndrome.12 In our patient, neurological symptoms and electromyography findings completely resolved after immunosuppressive therapy. In conclusion, both MCNS and stiff-person syndrome resolved completely with immunosuppressive therapy. As it was noted with stiffperson syndrome, an association between thyroiditis, diabetes mellitus (type 1),13 Guillain-Barré syndrome,14 and Graves disease15 with MCNS also was documented. These findings remind us that this is not only a coincidence, but there is a
¨ N ET AL ERGU
e14
meaningful link between MCNS and stiff-person syndrome. REFERENCES 1. Vanconcelos OM, Dalakas MC: Stiff-person syndrome. Curr Treat Options Neurol 5:79-90, 2003 2. Flocter MK: Inhibitory pathways defined by electrophysiology, in Levy LM (moderator): The stiff-person syndrome: An autoimmune disorder affecting neurotransmission of ␥-aminobutyric acid. Ann Intern Med 131:522-530, 1999 3. Hummel M, Durinovic-Bello I, Bonifacio E, et al: Humoral and cellular immune parameters before and during immunosuppressive therapy of a patient with stiff-man syndrome and insulin dependent diabetes mellitus. J Neurol Neurosurg Psychiatry 65:204-208, 1998 4. Goetz CG: Textbook of Clinical Neurology (ed 2). Philadelphia, PA, Elsevier, 2003, p 72 5. Chang T, Lang B: GAD antibodies in stiff-person syndrome. Neurology 63:1999-2000, 2004 6. Rakocevic G, Raju R, Dalakas MC: Anti-glutamic acid decarboxylase antibodies in the serum and cerebrospinal fluid of patients with stiff-person syndrome: Correlation with clinical severity. Arch Neurol 61:902-904, 2004 7. Costa M, Saiz A, Casamitjana R, et al: T-Cell reactivity to glutamic acid decarboxylase in stiff-man syndrome and cerebellar ataxia associated with polyendocrine autoimmunity. Clin Exp Immunol 129:471-478, 2002
8. Mathieson PW: Immune dysregulation in minimal change nephropathy. Nephrol Dial Transplant 18:S26-S29, 2003 (suppl 6) 9. Surany MG, Guasch A, Hall BM, Myers BD: Elevated levels of tumor necrosis factor-␣ in the nephrotic syndrome in humans. Am J Kidney Dis 21:251-259, 1993 10. Cunard R, Kelly CJ: T Cells and minimal change disease. J Am Soc Nephrol 13:1409-1411, 2002 11. Dalakas MC, Fujii M, Li M, Lutfi B, Kyhos J, McElroy B: High dose intravenous immune globulin for stiff-person syndrome. N Engl J Med 345:1870-1876, 2001 12. Wessig C, Klein R, Schneider MF, Toyka KV, Naumann M, Sommer C: Neuropathology and binding studies in anti-amphiphysin-associated stiff-person syndrome. Neurology 61:195-198, 2003 13. Kagiyama S, Tsuruta H, Tominaga M, et al: Minimal change nephrotic syndrome and acute renal failure in a patient with aged onset insulin-dependent diabetes mellitus and autoimmune thyroiditis. Am J Nephrol 19:369-372, 1999 14. Ilyas M, Tolaymat A: Minimal change nephrotic syndrome with Guillain-Barré syndrome. Pediatr Nephrol 19:105-106, 2004 15. Holt S, Kingdon E, Morganstein D, Sweny P: Simultaneous relapse of Graves’ disease and minimal change glomerular disease. Nephrol Dial Transplant 17:666-668, 2002
Minimal Change Nephrotic Syndrome With Stiff-Person Syndrome: Is There a Link? Ihsan Ergün, MD, M. Cenk Akbostanci, MD, Bas¸ol Canbakan, MD, Bilge Koçer, MD, Arzu Ensari, MD, Gökhan Nergizogˇlu, MD, and Kenan Keven, MD ● Stiff-person syndrome is a rare, likely immune-mediated neurological disorder characterized by painful spasms and progressive symmetric rigidity of the axial and proximal limb muscles. Rigidity of truncal muscles and continuous contraction of the agonist and antagonist muscles caused by involuntary motor-unit firing at rest are the hallmarks of stiff-person syndrome. Immunosuppressive therapy has induced remission in patients with stiff-person syndrome. We report a patient with stiff-person syndrome with minimal change nephrotic syndrome (MCNS). The pathophysiologic states of stiff-person syndrome and MCNS are unclear. T-Cell– dependent mechanisms are highly suspected for the pathogenesis of both. The diagnosis of stiff-person syndrome was made on the basis of clinical and laboratory findings, and both MCNS and stiff-person syndrome resolved completely with immunosuppressive therapy. To our knowledge, this is the first case of stiff-person syndrome in association with MCNS in the literature. Am J Kidney Dis 46:E11-E14. © 2005 by the National Kidney Foundation, Inc. INDEX WORDS: Minimal change disease; nephrotic syndrome; stiff-man syndrome; stiff-person syndrome.
S
TIFF-PERSON SYNDROME is a rare neurological disorder characterized by painful spasms and progressive symmetric rigidity of the axial and proximal limb muscles. Continuous contraction of the agonist and antagonist muscles caused by involuntary motor-unit firing at rest are the clinical and electrophysiological hallmarks of stiff-person syndrome. The diagnosis of stiff-person syndrome depends on clinical findings and the exclusion of other neurological disorders.1 Drugs that enhance ␥-aminobutyric acid neurotransmission are used for symptomatic treatment. Immunosuppressive therapy, including high doses of steroids, has resolved stiffperson syndrome. Although frequent associations between stiff-person syndrome and other autoimmune disorders, such as type 1 diabetes mellitus, thyroiditis, myasthenia gravis, pernicious anemia, and vitiligo, previously have been described,2,3 to the best of our knowledge, this is the first case of stiff-person syndrome in association with minimal change nephrotic syndrome (MCNS) for which T-cell–dependent mechanisms are highly suspected in the pathogenesis for both. CASE REPORT A 30-year-old man was referred to the hospital for investigation of recent painful spasms and stiffness in his back and proximal extremity muscles. He had felt painful spasms and muscular rigidity on his left shoulder and leg for 2 months. The rigidity was characterized by episodic painful spasms and stiffness. While the stiffness had been spreading to other areas of the body, including the trunk, peripheral edema
developed. He had difficulty walking and bending. He was not able to perform his routine daily activities. On admission, blood pressure was 100/70 mm Hg, and physical examination showed 2⫹⫹ pretibial pitting edema. During neurological examination, he had spasms superimposed on rigidity on his trunk and limbs. His gait was slow. His sensorial examination findings and muscle strength were normal. Deep-tendon reflexes were brisk. There was no evidence of myotonia or extrapyramidal or pyramidal dysfunction. During the examination, painful contraction of the trunk and limb muscles was noticed in both agonist and antagonist muscles. Electrophysiological study showed contractions of the agonist and antagonist muscles and continuous motor-unit activity in the lumbar paraspinal, rectus abdominis (Fig 1), bilateral anterior tibial, and gastrocnemius muscles at rest. Laboratory findings on admission were as follows: hemoglobin, 13.9 g/dL (139 g/L); total leukocyte count, 8,600/ L; serum creatinine, 0.7 mg/dL (62 mol/L); sedimentation rate, 17 mm/h; and C-reactive protein, 3.54 mg/L (normal range, 0 to 5 mg/L). He had proteinuria (protein, 8.9 g/d), hypoalbuminemia (albumin, 2.4 g/dL [24 g/L]), and hyperlipidemia (total cholesterol, 287 mg/dL [7.42 mmol/
From the Departments of Nephrology, Neurology, and Pathology, Ankara University School of Medicine, Ibni Sina Hospital, Ankara, Turkey. Received December 22, 2004; accepted in revised form March 14, 2005. Originally published online as doi:10.1053/j.ajkd.2005.03.009 on May 18, 2005. Address reprint requests to Ihsan Ergün, MD, Department of Nephrology, Ankara University School of Medicine, Ibni Sina Hospital, Sihhiye, 06100, Ankara, Turkey. E-mail: [email protected] or [email protected] © 2005 by the National Kidney Foundation, Inc. 0272-6386/05/4601-0031$30.00/0 doi:10.1053/j.ajkd.2005.03.009
American Journal of Kidney Diseases, Vol 46, No 1 (July), 2005: E11-E14
e11
¨ N ET AL ERGU
e12
Fig 1. Electromyographic activity of the patient at rest. Spontaneous spasms in the right lumbar paraspinal and rectus abdominis muscles.
L]; triglyceride, 274 mg/dL [3.09 mmol/L]). Urine microscopic examination showed no erythrocytes or casts. Serum lactate dehydrogenase (142 U/L) and creatine phosphokinase (32 U/L) levels were normal. Test results for antinuclear antibody, antineutrophil cytoplasmic antibody, hepatitis B virus surface antigen, hepatitis C virus antibody, and human immunodeficiency virus antibody were negative. Other biochemical parameters, complement levels (C3c and C4), and cerebrospinal fluid were normal. Immune electrophoresis showed no evidence of a paraprotein. A renal biopsy was performed for nephrotic syndrome. Evaluation of light microscopy was normal, with negative immunofluorescence findings, and electron microscopy showed diffuse foot-process fusion without electron-dense deposits, compatible with minimal change disease. The diagnosis of stiff-person syndrome was based on the patient’s history, neurological examination, and electrophysiological findings. To exclude a malignancy, a computed tomographic scan of the thorax, magnetic resonance image of the brain, ultrasonographic evaluation of the abdomen, gastroscopy, and colonoscopy were performed, and all showed normal results.
Fig 2. Electromyographic activity of the patient at rest. Return to normal.
After the diagnosis, diazepam, 10 mg/d, was administered, and neurological symptoms regressed partially. After documentation of MCNS, 3-day methylprednisolone (500 mg/d) pulse therapy was initiated, followed by oral prednisolone (1 mg/kg/d) with cyclophosphamide (2 mg/kg/d). Oral prednisolone therapy was continued for a month with the same dose, then tapered slowly to 0.3 mg/kg/d. Month 2, nephrotic syndrome remitted partially, and month 3, proteinuria completely disappeared. Control serum albumin level was 4 g/dL (40 g/L). After remission, the cyclophosphamide dose was tapered to 1 mg/kg/d. Oral prednisolone and cyclophosphamide therapy was continued for 6 months, then stopped. Neurological symptoms and findings completely disappeared after pulse therapy, with normalization of electromyographic findings (Fig 2). Diazepam therapy was discontinued after 6 months. No recurrence was noticed during 1 year after cessation of the therapy.
DISCUSSION
Stiff-person syndrome is a rare central nervous system disorder characterized by progres-
MCNS WITH STIFF-PERSON SYNDROME
sive stiffness of predominantly axial and proximal limb muscles. Diagnosis of this rare condition depends on the clinical findings of axial and proximal limb rigidity, painful spasms, and normal neurological findings, except for brisk deeptendon reflexes.1 Our patient had painful spasms and stiffness in his back and proximal muscles. His neurological examination findings were normal, except for brisk deep-tendon reflexes. For definitive diagnosis, it is important to show continuous muscle activity in the trunk and proximal limb muscles at rest. We performed electromyography, showing simultaneous motor-unit firing of the lumbar paraspinal and rectus abdominis muscles at rest. Dystonia and orthostatic tremor are the primary disorders that should be considered in the differential diagnosis of stiff-person syndrome. Patients may report pain and muscle cramping in both disorders, but the symptoms are seen especially when standing and during motion in dystonia. Tetanus, progressive encephalomyelitis with rigidity, and Isaacs sydrome are the rare conditions resembling stiff-person syndrome.4 The pathophysiological states of stiff-person syndrome and MCNS are unclear, but likely are immune mediated, and T cells have a key role in the pathogenesis of both. Patients with stiff-person syndrome have antibodies against glutamic acid decarboxylase (GAD), which catalyzes the conversion of glutamic acid to ␥-aminobutyric acid, the major inhibitory neurotransmitter in the central nervous system. Antibodies to GAD are detected in approximately 60% to 80% of patients with stiff-person syndrome, but also have been seen in neurological and non-neurological diseases without rigidity or spasm.5 Although anti-GAD antibodies are an excellent marker6 for stiff-person syndrome, we were not able to check anti-GAD antibodies in our patient. However, it should be considered that anti-GAD antibodies are neither essential for the diagnosis of stiff-person syndrome3 nor a follow-up marker for stiff-person syndrome.6 When the disease is active or in relapse, T-cell proliferation against GAD and cytokine release from antigen-stimulated T cells (interferon ␥) were determined.3 In patients with stiff-person syndrome, GADspecific cellular proliferation, the synthesis of cytoplasmic interleukin 4, and interferon ␥ levels
e13
produced by activated T cells were significantly greater than in healthy controls.7 Although antibody concentrations against GAD showed no correlation with neurological symptoms, increased T-cell reactivity has an evident correlation. High doses of steroids, despite having no effect on antibody titers, can induce remission in patients with stiff-person syndrome.3 Similarly, many observations suggest a link between MCNS and T lymphocytes. A complex immune dysfunction is present in patients with MCNS. Investigations focused on soluble factors produced by activated T cells that alter and increase glomerular permeability to protein. TCell–dependent type 2 cytokines are predominant and can directly or indirectly cause MCNS.8 Certain cytokines, such as tumor necrosis factor ␣, have been implicated as a possible pathogenic factor in the mechanism of renal injury in patients with nephrotic syndrome.9 A well-documented association with lymphoma, remission of MCNS with measles infection (viral-associated immunosuppression), overexpression of lymphokines (interleukins 4 and 13) in relapse, depression of recall responses to common antigens or delayed cutaneous hypersensitivity reactions, and response to immunosuppressive therapy support the role of T cells in the pathogenesis of MCNS.8,10 Drugs that enhance ␥-aminobutyric acid neurotransmission, such as diazepam, baclofen, clonazepam, valproic acid, and clonidine, have improved clinical symptoms.1,2 Immunosuppressive agents, plasmapheresis, and immunoglobulin therapy11 have been found to be an effective treatment. We treated this patient with prednisolone and cyclophosphamide. Although it was not conventional for MCNS, cyclophosphamide has been shown to increase the response to therapy in stiff-person syndrome.12 In our patient, neurological symptoms and electromyography findings completely resolved after immunosuppressive therapy. In conclusion, both MCNS and stiff-person syndrome resolved completely with immunosuppressive therapy. As it was noted with stiffperson syndrome, an association between thyroiditis, diabetes mellitus (type 1),13 Guillain-Barré syndrome,14 and Graves disease15 with MCNS also was documented. These findings remind us that this is not only a coincidence, but there is a
¨ N ET AL ERGU
e14
meaningful link between MCNS and stiff-person syndrome. REFERENCES 1. Vanconcelos OM, Dalakas MC: Stiff-person syndrome. Curr Treat Options Neurol 5:79-90, 2003 2. Flocter MK: Inhibitory pathways defined by electrophysiology, in Levy LM (moderator): The stiff-person syndrome: An autoimmune disorder affecting neurotransmission of ␥-aminobutyric acid. Ann Intern Med 131:522-530, 1999 3. Hummel M, Durinovic-Bello I, Bonifacio E, et al: Humoral and cellular immune parameters before and during immunosuppressive therapy of a patient with stiff-man syndrome and insulin dependent diabetes mellitus. J Neurol Neurosurg Psychiatry 65:204-208, 1998 4. Goetz CG: Textbook of Clinical Neurology (ed 2). Philadelphia, PA, Elsevier, 2003, p 72 5. Chang T, Lang B: GAD antibodies in stiff-person syndrome. Neurology 63:1999-2000, 2004 6. Rakocevic G, Raju R, Dalakas MC: Anti-glutamic acid decarboxylase antibodies in the serum and cerebrospinal fluid of patients with stiff-person syndrome: Correlation with clinical severity. Arch Neurol 61:902-904, 2004 7. Costa M, Saiz A, Casamitjana R, et al: T-Cell reactivity to glutamic acid decarboxylase in stiff-man syndrome and cerebellar ataxia associated with polyendocrine autoimmunity. Clin Exp Immunol 129:471-478, 2002
8. Mathieson PW: Immune dysregulation in minimal change nephropathy. Nephrol Dial Transplant 18:S26-S29, 2003 (suppl 6) 9. Surany MG, Guasch A, Hall BM, Myers BD: Elevated levels of tumor necrosis factor-␣ in the nephrotic syndrome in humans. Am J Kidney Dis 21:251-259, 1993 10. Cunard R, Kelly CJ: T Cells and minimal change disease. J Am Soc Nephrol 13:1409-1411, 2002 11. Dalakas MC, Fujii M, Li M, Lutfi B, Kyhos J, McElroy B: High dose intravenous immune globulin for stiff-person syndrome. N Engl J Med 345:1870-1876, 2001 12. Wessig C, Klein R, Schneider MF, Toyka KV, Naumann M, Sommer C: Neuropathology and binding studies in anti-amphiphysin-associated stiff-person syndrome. Neurology 61:195-198, 2003 13. Kagiyama S, Tsuruta H, Tominaga M, et al: Minimal change nephrotic syndrome and acute renal failure in a patient with aged onset insulin-dependent diabetes mellitus and autoimmune thyroiditis. Am J Nephrol 19:369-372, 1999 14. Ilyas M, Tolaymat A: Minimal change nephrotic syndrome with Guillain-Barré syndrome. Pediatr Nephrol 19:105-106, 2004 15. Holt S, Kingdon E, Morganstein D, Sweny P: Simultaneous relapse of Graves’ disease and minimal change glomerular disease. Nephrol Dial Transplant 17:666-668, 2002