Neurol Sci DOI 10.1007/s10072-014-1660-5
LETTER TO THE EDITOR
Parkinson’s disease associated with myasthenia gravis and rheumatoid arthritis Panagiotis Zis • Vassiliki Argiriadou • Prodromos P. Temperikidis • Lamprini Zikou Socrates J. Tzartos • Antonios Tavernarakis
•
Received: 18 January 2014 / Accepted: 24 January 2014 Ó Springer-Verlag Italia 2014
Introduction Accumulating evidence supports a possible role of the immune system in Parkinson’s disease (PD) pathogenesis, either through inflammation or by an autoimmune response [1].
Case A 69-year-old Caucasian man came to our attention for a progressive weakness in the flexion of his neck that started 2 months before, becoming worse over the last week. The weakness did not show a pronounced diurnal variation. Past history included well-controlled arterial hypertension, and a 5-year history of PD (Fig. 1). On admission the patient was alert and orientated. General physical examination was unremarkable. On neurological examination, the strength of the neck extensors was reduced to 2/5 according to the Medical Research Council’s score, the strength of both sternocleidomastoids was 3/5, the strength of the left deltoid was 3/5 and the strength of the right deltoid was 4/5. All the remaining
P. Zis (&) V. Argiriadou L. Zikou A. Tavernarakis Department of Neurology, Evangelismos General Hospital, 45-47 Ipsilantou Str., 10676 Athens, Greece e-mail: [email protected] P. P. Temperikidis 1st Critical Care Medicine Department, Evangelismos Hospital, National Kapodistrian University of Athens, Athens, Greece S. J. Tzartos Hellenic Pasteur Institute, and Tzartos Neurodiagnostics, Athens, Greece
muscles were scored 5/5. Left hand rigidity was also noted. Routine blood and urine exams were unremarkable, apart from a slightly elevated C-reactive protein (CRP = 1.3 mg/dL, normal values = 0–0.5 mg/dL). On day 2, MRI of the cervical spine was performed and was normal. However, neurophysiological testing showed positive rapid decremental responses of muscle action potentials to repetitive nerve stimulation. A chest axial computed tomography did not reveal the presence of a thymoma or a thymus gland enlargement. Further immunology screening revealed an elevated acetylcholine receptor (AChR) antibody count (titer 142, 5 nmol/L, normal values \0.5 nmol/L) when antibodies to muscle-specific tyrosine kinase (MuSK) and antibodies against presynaptic voltage-gated calcium channels were negative. A diagnosis of myasthenia gravis (MG) was set and pyridostigmine bromide (60 mg 9 4) and prednisolone (10 mg) were commenced. On the third day of hospitalization, the patient complained of an acute left knee pain. Clinical examination revealed monoarthritis of the joint. In a subsequent arthrocentesis, 27 cc of synovial fluid (yellow cloudy before centrifugation, yellow transparent after centrifugation) were aspirated. The analysis showed very high white cell count (168,600 cells per mm3, 90 % of which neutrophils). Further microscopy did not show presence of any crystals. Synovial fluid culture result was negative. Moreover, serum CRP was 9.8 mg/dL and continued to elevate over the next days to a maximum of 27.6 mg/dL. Further immunology screening was negative for rheumatoid factor, however, it was positive for anti-citrullinated protein antibodies (anti-CCP) (titer [500 IU/mL, normal values 0.1–25 IU/mL). The prednisolone was increased to 75 mg once daily. Over the following days the symptoms of arthritis subsided and the CRP went back to normal. Moreover,
123
Fig. 1 Patient a on admission, b at discharge. Dropped head dramatically improved after treatment
pyridostigmine and prednisolone improved significantly the patient’s weakness in the flexion of his neck. The patient was discharged in a good clinical condition.
Discussion
Ueno was the first to describe a patient where PD and MG coexisted [2]. However, since then a possible link between PD and MG has been suggested in eight more published cases [3–7]; their demographic and clinical characteristics are summarized in Table 1. Our patient is the tenth to be reported where these two medical entities coexist. A male predominance, of approximately 2:1, has been observed. The majority of the patients had a diagnosis of
123
Ueno et al.
Kao et al.
Levin et al.
Fasano et al. Unal-Cevik and Temucin
Uldag et al.
Zis et al. (this report)
1987
1993
2003
2008 2009
2011
2013
Author
Year
MG PD
Case #3 Case #4
Single case
Single case PD
PD
PD PD
PD
Single case Single case
PD
Case #2
PD
PD
First diagnosis
Case #1
Single case
Single case
Case/case series
69
75
58 84
61
68
62
76
62
60
Age at second diagnosis
M
M
F M
M
F
M
M
F
M
Sex
Table 1 Demographic and clinical characteristics of published data of patients suffering from PD and MG
AChR (?) Anti-musk (-)
AChR (?)
AChR (-) Anti-MuSK (-) AChR (-)
n/a
AChR (?)
AChR (?)
AChR (?)
AChR (?)
AChR (?)
Antibodies detected
Dropped head
Dropped head
Dropped head Dropped head
Bilateral ptosis
Limb weakness and ptosis
Unilateral ptosis, lower limb weakness, diplopia, dysphagia and dyspnea
Dropped head
Unilateral ptosis, diplopia, slurred speech and generalized weakness
Dropped head, ptosis, diplopia
MG presenting symptom
Neurol Sci
Neurol Sci
PD, and MG was diagnosed few years later. Only in one patient MG predisposed PD [4]. Seven patients were positive for AChR antibodies, two were negative, and for one there is no information available. Interestingly, five patients presented with a head drop as the first manifestation of MG, when in four of them head drop was the sole manifestation of MG. Along with the deterioration of weakness in the flexion of his neck, our patient developed monoarthritis of his left knee. The very high white cell count was in favor of septic arthritis. However, as synovial fluid culture was negative, septic arthritis was excluded from the differential diagnosis. The absence of any crystals, the normal serum uric acid and the very high anti-CCP titer, made rheumatoid arthritis (RA) the most likely diagnosis. In the past, observations of extrapyramidal-type rigidity in RA patients have lead to the hypothesis that these patients are at increased risk of PD [8]. To our knowledge, this is the first case where a patient with PD has also been diagnosed with two different autoimmune medical conditions, occurring simultaneously. Although we cannot exclude the possibility of this being a coincidence, we believe that this case supports the increasing evidence for an involvement of the immune system in PD pathogenesis.
Acknowledgments We are sincerely thankful to the patient and to Dr Valsamoula Myridaki for her contribution in the clinical management of the case.
References 1. Koutsilieri E, Lutz MB, Scheller C (2013) Autoimmunity, dendritic cells and relevance for Parkinson’s disease. J Neural Transm 120(1):75–81 2. Ueno S, Takahashi M, Kajiyama K et al (1987) Parkinson’s disease and myasthenia gravis: adverse effect of trihexyphenidyl on neuromuscular transmission. Neurology 37(5):832–833 3. Kao KP, Kwan SY, Lin KP et al (1993) Coexistence of Parkinson’s disease and myasthenia gravis: a case report. Clin Neurol Neurosurg 95(2):137–139 4. Levin N, Karussis D, Abramsky O (2003) Parkinson’s disease associated with myasthenia gravis. A report of 4 cases. J Neurol 250(6):766–767 5. Fasano A, Evoli A, Piano C et al (2008) Myasthenia gravis: an unrecognized cause of head drop in Parkinson’s disease. Parkinsonism Relat Disord 14(2):164–165 6. Unal-Cevik I, Temucin CM (2009) Head drop in an elder Parkinson’s disease after development of myasthenia gravis. Mov Disord 24(13):2025–2026 7. Uludag IF, Korucuk M, Sener U et al (2011) Myasthenia gravis as a cause of head drop in Parkinson disease. Neurologist 17(3):144–146 8. Kogure T, Tatsumi T, Kaneko Y et al (2008) Rheumatoid arthritis accompanied by Parkinson disease. J Clin Rheumatol 14(3):192–193
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LETTER TO THE EDITOR
Parkinson’s disease associated with myasthenia gravis and rheumatoid arthritis Panagiotis Zis • Vassiliki Argiriadou • Prodromos P. Temperikidis • Lamprini Zikou Socrates J. Tzartos • Antonios Tavernarakis
•
Received: 18 January 2014 / Accepted: 24 January 2014 Ó Springer-Verlag Italia 2014
Introduction Accumulating evidence supports a possible role of the immune system in Parkinson’s disease (PD) pathogenesis, either through inflammation or by an autoimmune response [1].
Case A 69-year-old Caucasian man came to our attention for a progressive weakness in the flexion of his neck that started 2 months before, becoming worse over the last week. The weakness did not show a pronounced diurnal variation. Past history included well-controlled arterial hypertension, and a 5-year history of PD (Fig. 1). On admission the patient was alert and orientated. General physical examination was unremarkable. On neurological examination, the strength of the neck extensors was reduced to 2/5 according to the Medical Research Council’s score, the strength of both sternocleidomastoids was 3/5, the strength of the left deltoid was 3/5 and the strength of the right deltoid was 4/5. All the remaining
P. Zis (&) V. Argiriadou L. Zikou A. Tavernarakis Department of Neurology, Evangelismos General Hospital, 45-47 Ipsilantou Str., 10676 Athens, Greece e-mail: [email protected] P. P. Temperikidis 1st Critical Care Medicine Department, Evangelismos Hospital, National Kapodistrian University of Athens, Athens, Greece S. J. Tzartos Hellenic Pasteur Institute, and Tzartos Neurodiagnostics, Athens, Greece
muscles were scored 5/5. Left hand rigidity was also noted. Routine blood and urine exams were unremarkable, apart from a slightly elevated C-reactive protein (CRP = 1.3 mg/dL, normal values = 0–0.5 mg/dL). On day 2, MRI of the cervical spine was performed and was normal. However, neurophysiological testing showed positive rapid decremental responses of muscle action potentials to repetitive nerve stimulation. A chest axial computed tomography did not reveal the presence of a thymoma or a thymus gland enlargement. Further immunology screening revealed an elevated acetylcholine receptor (AChR) antibody count (titer 142, 5 nmol/L, normal values \0.5 nmol/L) when antibodies to muscle-specific tyrosine kinase (MuSK) and antibodies against presynaptic voltage-gated calcium channels were negative. A diagnosis of myasthenia gravis (MG) was set and pyridostigmine bromide (60 mg 9 4) and prednisolone (10 mg) were commenced. On the third day of hospitalization, the patient complained of an acute left knee pain. Clinical examination revealed monoarthritis of the joint. In a subsequent arthrocentesis, 27 cc of synovial fluid (yellow cloudy before centrifugation, yellow transparent after centrifugation) were aspirated. The analysis showed very high white cell count (168,600 cells per mm3, 90 % of which neutrophils). Further microscopy did not show presence of any crystals. Synovial fluid culture result was negative. Moreover, serum CRP was 9.8 mg/dL and continued to elevate over the next days to a maximum of 27.6 mg/dL. Further immunology screening was negative for rheumatoid factor, however, it was positive for anti-citrullinated protein antibodies (anti-CCP) (titer [500 IU/mL, normal values 0.1–25 IU/mL). The prednisolone was increased to 75 mg once daily. Over the following days the symptoms of arthritis subsided and the CRP went back to normal. Moreover,
123
Fig. 1 Patient a on admission, b at discharge. Dropped head dramatically improved after treatment
pyridostigmine and prednisolone improved significantly the patient’s weakness in the flexion of his neck. The patient was discharged in a good clinical condition.
Discussion
Ueno was the first to describe a patient where PD and MG coexisted [2]. However, since then a possible link between PD and MG has been suggested in eight more published cases [3–7]; their demographic and clinical characteristics are summarized in Table 1. Our patient is the tenth to be reported where these two medical entities coexist. A male predominance, of approximately 2:1, has been observed. The majority of the patients had a diagnosis of
123
Ueno et al.
Kao et al.
Levin et al.
Fasano et al. Unal-Cevik and Temucin
Uldag et al.
Zis et al. (this report)
1987
1993
2003
2008 2009
2011
2013
Author
Year
MG PD
Case #3 Case #4
Single case
Single case PD
PD
PD PD
PD
Single case Single case
PD
Case #2
PD
PD
First diagnosis
Case #1
Single case
Single case
Case/case series
69
75
58 84
61
68
62
76
62
60
Age at second diagnosis
M
M
F M
M
F
M
M
F
M
Sex
Table 1 Demographic and clinical characteristics of published data of patients suffering from PD and MG
AChR (?) Anti-musk (-)
AChR (?)
AChR (-) Anti-MuSK (-) AChR (-)
n/a
AChR (?)
AChR (?)
AChR (?)
AChR (?)
AChR (?)
Antibodies detected
Dropped head
Dropped head
Dropped head Dropped head
Bilateral ptosis
Limb weakness and ptosis
Unilateral ptosis, lower limb weakness, diplopia, dysphagia and dyspnea
Dropped head
Unilateral ptosis, diplopia, slurred speech and generalized weakness
Dropped head, ptosis, diplopia
MG presenting symptom
Neurol Sci
Neurol Sci
PD, and MG was diagnosed few years later. Only in one patient MG predisposed PD [4]. Seven patients were positive for AChR antibodies, two were negative, and for one there is no information available. Interestingly, five patients presented with a head drop as the first manifestation of MG, when in four of them head drop was the sole manifestation of MG. Along with the deterioration of weakness in the flexion of his neck, our patient developed monoarthritis of his left knee. The very high white cell count was in favor of septic arthritis. However, as synovial fluid culture was negative, septic arthritis was excluded from the differential diagnosis. The absence of any crystals, the normal serum uric acid and the very high anti-CCP titer, made rheumatoid arthritis (RA) the most likely diagnosis. In the past, observations of extrapyramidal-type rigidity in RA patients have lead to the hypothesis that these patients are at increased risk of PD [8]. To our knowledge, this is the first case where a patient with PD has also been diagnosed with two different autoimmune medical conditions, occurring simultaneously. Although we cannot exclude the possibility of this being a coincidence, we believe that this case supports the increasing evidence for an involvement of the immune system in PD pathogenesis.
Acknowledgments We are sincerely thankful to the patient and to Dr Valsamoula Myridaki for her contribution in the clinical management of the case.
References 1. Koutsilieri E, Lutz MB, Scheller C (2013) Autoimmunity, dendritic cells and relevance for Parkinson’s disease. J Neural Transm 120(1):75–81 2. Ueno S, Takahashi M, Kajiyama K et al (1987) Parkinson’s disease and myasthenia gravis: adverse effect of trihexyphenidyl on neuromuscular transmission. Neurology 37(5):832–833 3. Kao KP, Kwan SY, Lin KP et al (1993) Coexistence of Parkinson’s disease and myasthenia gravis: a case report. Clin Neurol Neurosurg 95(2):137–139 4. Levin N, Karussis D, Abramsky O (2003) Parkinson’s disease associated with myasthenia gravis. A report of 4 cases. J Neurol 250(6):766–767 5. Fasano A, Evoli A, Piano C et al (2008) Myasthenia gravis: an unrecognized cause of head drop in Parkinson’s disease. Parkinsonism Relat Disord 14(2):164–165 6. Unal-Cevik I, Temucin CM (2009) Head drop in an elder Parkinson’s disease after development of myasthenia gravis. Mov Disord 24(13):2025–2026 7. Uludag IF, Korucuk M, Sener U et al (2011) Myasthenia gravis as a cause of head drop in Parkinson disease. Neurologist 17(3):144–146 8. Kogure T, Tatsumi T, Kaneko Y et al (2008) Rheumatoid arthritis accompanied by Parkinson disease. J Clin Rheumatol 14(3):192–193
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