Neurol Sci DOI 10.1007/s10072-014-1699-3
LETTER TO THE EDITOR
Parkinsonism as an initial manifestation of rheumatoid meningitis Yuka Hayashi • Michito Namekawa • Keisuke Ohtani • Eiju Watanabe • Imaharu Nakano
Received: 28 December 2013 / Accepted: 20 February 2014 Ó Springer-Verlag Italia 2014
Dear Sir, Rheumatoid meningitis (RM) has been considered to be an extremely rare complication of rheumatoid arthritis (RA), which itself is very common [1]. However, due to better access to MRI, RM has been increasingly diagnosed. More than 30 cases diagnosed by MRI and pathology have been reported [2–4]. In most cases, onset occurred after the age of 50 in both sexes. The clinical symptoms and signs and the MRI findings were those of non-specific chronic leptomeningitis [5]. Of interest, there were no associations between the onset and activity of RM, the severity and activity of synovitis, the duration of RA or the way it treated [3]. We have described here for the first time a patient with pathologically proven RM the initial symptom of which was parkinsonism. A 68-year-old Japanese man with a 10-year history of RA treated successfully with prednisolone (6 mg/day) was referred to a regional hospital because of a bilateral resting tremor predominating on the right side, progressive gait instability that began by hesitation and bradykinesia. He was diagnosed as having Parkinson’s disease, but his symptoms did not respond to levodopa. He soon developed a progressive cognitive dysfunction, accompanied by a
Y. Hayashi M. Namekawa (&) Department of Neurology, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan e-mail: [email protected] K. Ohtani E. Watanabe Department of Neurosurgery, Jichi Medical University School of Medicine, Shimotsuke, Japan I. Nakano Tokyo Metropolitan Neurological Hospital, Tokyo, Japan
slight fever, followed 2 months later by urinary incontinence. In spite of more than 3 months of treatment with antibiotics, antiviral agents and antimycotics, his condition gradually deteriorated and he was transferred to our university hospital. On admission, he was apathetic and bedridden. Disuse atrophy was generalized, and he had severe bilateral swanneck deformities of his fingers due to RA. His face was mask-like, and his verbal responses were very slow with muted monotonous voice. His Mini-Mental State Examination (MMSE) score was 11. Bradykinesia was remarkable, and rigidity was seen in the neck and all extremities. Resting tremor was observed intermittently in both hands. Laboratory data suggested inactive RA. Cerebrospinal fluid (CSF), analyzed after lumbar puncture, was clear, and pressure was normal. The cell count was slightly increased (13/mm3), but there were no atypical cells. Protein levels were increased (75 mg/dL), but glucose levels were normal. Results of cell cultures performed repeatedly, immunological investigations, a polymerase chain reaction (PCR) to detect microorganisms, and cytological investigations of the CSF were all negative. No malignancy was detected by a whole body CT scan with enhancement. Brain MRI with contrast enhancement (Fig. 1a, b) revealed a diffuse meningeal lesion. Secondary hydrocephalus was also observed (Fig.1c). A biopsy of the leptomeninx together with adjacent brain parenchyma from the right frontal lobe revealed foci of necrotic tissue in the subarachnoid space surrounded by chronic inflammatory cells consisting of numerous lymphocytes, plasma cells, a few neutrophils and scattered giant multinucleated cells (Fig. 1e, f). No inflammation was seen in the dura mater and parenchyma per se. These pathological findings associated with the negative laboratory data were consistent with a diagnosis of RM.
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Fig. 1 MRI, macroscopic and microscopic findings in a patient with rheumatoid meningitis. a, b Axial section of a T1-weighted image (T1-WI) with gadolinium enhancement (a) and a diffusion-weighted image (DWI) (b) revealing diffuse meningeal involvement, apparently reflecting the presence of an abscess or proteinaceous debris. c Coronal section of a T1-WI with enhancement showing diffuse meningeal involvement as well as enlargement of the lateral
ventricles indicative of secondary hydrocephalus. d An intraoperative photograph showing a cloudy brain surface reflecting subarachnoidal empyema. e, f Biopsy specimens from the right frontal lobe showing diffuse inflammatory cell infiltration in the leptomeninx. Giant multinuclear cells (arrows) were seen in a magnification of the region delimited by the square (f)
The patient received steroid pulse therapy (1,000 mg/ day of methylprednisolone) for 3 days, followed by oral administration of prednisolone (40 mg/day). His cognitive dysfunction and bradyphrenia gradually improved and after a month of treatment, his MMSE score was 22. The meningeal enhancement and hyperintense lesions on the diffusion-weighted image (DWI) were no longer seen on the follow-up MRI. However, his hydrocephalus remained unchanged. The dose of prednisolone was decreased by 5 mg/day every 4 weeks until a maintenance dose of 10 mg/day was reached. Levodopa/carbidopa hydrate (up to 600 mg/60 mg per day) was again prescribed, but did not relieve the tremor, rigidity or bradykinesia. After 2 years without a recurrence of RM, his clinical condition,
including levodopa-resistant parkinsonism and the hydrocephalus observed on brain MRI, remained unchanged, but the patient himself and members of his family were satisfied with his present status and refused further invasive procedures. To our knowledge, this is the first report of parkinsonism in RM. Unlike the patchy/focal lesions of the leptomeninx seen in most cases of RM [2, 4], diffuse leptomeningeal involvement developed in the patient, presumably causing the secondary hydrocephalus. Approximately 10 % of adult hydrocephalus patients develop parkinsonism (rigidity and/or resting tremor in addition to bradykinesia and gait disturbance) [6, 7]. In some cases, especially those in which acute
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hydrocephalus develops due to shunt obstruction, levodopa has a dramatic effect [6, 8]. The physiopathology might involve reversible dysfunction of the presynaptic nigrostriatal dopaminergic pathway adjacent to the expanded third ventricle [6]. The absence of a response to levodopa in our patient suggests that the not only nigrostriatal system but also other basal ganglia circuits, including the striatum and its projections to motor and/or supplemental motor areas in the frontal lobe, were dysfunctional [6]. In conclusion, we have described the first case of parkinsonism associated with RM, presumably caused by secondary hydrocephalus. Additional reports of similar cases would help to elucidate the clinical features and pathogenesis of this condition and to develop effective therapeutic strategies. Acknowledgments We are very grateful to Dr. Merle Ruberg for critical reading of this manuscript. Conflict of interest interest.
The authors declare that there is no conflict of
References 1. Bathon JM, Moreland LW, DiBartolomeo AG (1989) Inflammatory central nervous system involvement in rheumatoid arthritis. Semin Arthr Rheum 18:258–266 2. Kato T, Hoshi K, Sekijima Y et al (2003) Rheumatoid meningitis: an autopsy report and review of the literature. Clin Rheumatol 22:475–480 3. Shimada K, Matsui T, Kawakami M et al (2009) Diffuse chronic leptomeningitis with seropositive rheumatoid arthritis: report of a case successfully treated as rheumatoid leptomeningitis. Mod Rheumatol 19:556–562 4. Hasiloglu ZI, Asik M, Erer B, Eikici AS, Altintas A, Albayram S (2012) Magnetic resonance imaging of rheumatoid meningitis: a case report and literature review. Rheumatol Int 32:3679–3681 5. Hildebrand J, Aoun M (2003) Chronic meningitis: still a diagnostic challenge. J Neurol 250:653–660 6. Curran T, Lang AE (1994) Parkinsonian syndromes associated with hydrocephalus: case reports, a review of the literature, and pathophysiological hypotheses. Mov Disord 9:508–520 7. Krauss JK, Regal JP, Droste DW, Orszagh M, Borremans JJ, Vach W (1997) Movement disorder in adult hydrocephalus. Mov Disord 12:53–60 8. Kim MJ, Chung SJ, Sung YH, Lee MC, Im JH (2006) Levodoparesponsive parkinsonism associated with hydrocephalus. Mov Disord 21:1279–1281
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LETTER TO THE EDITOR
Parkinsonism as an initial manifestation of rheumatoid meningitis Yuka Hayashi • Michito Namekawa • Keisuke Ohtani • Eiju Watanabe • Imaharu Nakano
Received: 28 December 2013 / Accepted: 20 February 2014 Ó Springer-Verlag Italia 2014
Dear Sir, Rheumatoid meningitis (RM) has been considered to be an extremely rare complication of rheumatoid arthritis (RA), which itself is very common [1]. However, due to better access to MRI, RM has been increasingly diagnosed. More than 30 cases diagnosed by MRI and pathology have been reported [2–4]. In most cases, onset occurred after the age of 50 in both sexes. The clinical symptoms and signs and the MRI findings were those of non-specific chronic leptomeningitis [5]. Of interest, there were no associations between the onset and activity of RM, the severity and activity of synovitis, the duration of RA or the way it treated [3]. We have described here for the first time a patient with pathologically proven RM the initial symptom of which was parkinsonism. A 68-year-old Japanese man with a 10-year history of RA treated successfully with prednisolone (6 mg/day) was referred to a regional hospital because of a bilateral resting tremor predominating on the right side, progressive gait instability that began by hesitation and bradykinesia. He was diagnosed as having Parkinson’s disease, but his symptoms did not respond to levodopa. He soon developed a progressive cognitive dysfunction, accompanied by a
Y. Hayashi M. Namekawa (&) Department of Neurology, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan e-mail: [email protected] K. Ohtani E. Watanabe Department of Neurosurgery, Jichi Medical University School of Medicine, Shimotsuke, Japan I. Nakano Tokyo Metropolitan Neurological Hospital, Tokyo, Japan
slight fever, followed 2 months later by urinary incontinence. In spite of more than 3 months of treatment with antibiotics, antiviral agents and antimycotics, his condition gradually deteriorated and he was transferred to our university hospital. On admission, he was apathetic and bedridden. Disuse atrophy was generalized, and he had severe bilateral swanneck deformities of his fingers due to RA. His face was mask-like, and his verbal responses were very slow with muted monotonous voice. His Mini-Mental State Examination (MMSE) score was 11. Bradykinesia was remarkable, and rigidity was seen in the neck and all extremities. Resting tremor was observed intermittently in both hands. Laboratory data suggested inactive RA. Cerebrospinal fluid (CSF), analyzed after lumbar puncture, was clear, and pressure was normal. The cell count was slightly increased (13/mm3), but there were no atypical cells. Protein levels were increased (75 mg/dL), but glucose levels were normal. Results of cell cultures performed repeatedly, immunological investigations, a polymerase chain reaction (PCR) to detect microorganisms, and cytological investigations of the CSF were all negative. No malignancy was detected by a whole body CT scan with enhancement. Brain MRI with contrast enhancement (Fig. 1a, b) revealed a diffuse meningeal lesion. Secondary hydrocephalus was also observed (Fig.1c). A biopsy of the leptomeninx together with adjacent brain parenchyma from the right frontal lobe revealed foci of necrotic tissue in the subarachnoid space surrounded by chronic inflammatory cells consisting of numerous lymphocytes, plasma cells, a few neutrophils and scattered giant multinucleated cells (Fig. 1e, f). No inflammation was seen in the dura mater and parenchyma per se. These pathological findings associated with the negative laboratory data were consistent with a diagnosis of RM.
123
Neurol Sci
A
B
E
C
F
D
Fig. 1 MRI, macroscopic and microscopic findings in a patient with rheumatoid meningitis. a, b Axial section of a T1-weighted image (T1-WI) with gadolinium enhancement (a) and a diffusion-weighted image (DWI) (b) revealing diffuse meningeal involvement, apparently reflecting the presence of an abscess or proteinaceous debris. c Coronal section of a T1-WI with enhancement showing diffuse meningeal involvement as well as enlargement of the lateral
ventricles indicative of secondary hydrocephalus. d An intraoperative photograph showing a cloudy brain surface reflecting subarachnoidal empyema. e, f Biopsy specimens from the right frontal lobe showing diffuse inflammatory cell infiltration in the leptomeninx. Giant multinuclear cells (arrows) were seen in a magnification of the region delimited by the square (f)
The patient received steroid pulse therapy (1,000 mg/ day of methylprednisolone) for 3 days, followed by oral administration of prednisolone (40 mg/day). His cognitive dysfunction and bradyphrenia gradually improved and after a month of treatment, his MMSE score was 22. The meningeal enhancement and hyperintense lesions on the diffusion-weighted image (DWI) were no longer seen on the follow-up MRI. However, his hydrocephalus remained unchanged. The dose of prednisolone was decreased by 5 mg/day every 4 weeks until a maintenance dose of 10 mg/day was reached. Levodopa/carbidopa hydrate (up to 600 mg/60 mg per day) was again prescribed, but did not relieve the tremor, rigidity or bradykinesia. After 2 years without a recurrence of RM, his clinical condition,
including levodopa-resistant parkinsonism and the hydrocephalus observed on brain MRI, remained unchanged, but the patient himself and members of his family were satisfied with his present status and refused further invasive procedures. To our knowledge, this is the first report of parkinsonism in RM. Unlike the patchy/focal lesions of the leptomeninx seen in most cases of RM [2, 4], diffuse leptomeningeal involvement developed in the patient, presumably causing the secondary hydrocephalus. Approximately 10 % of adult hydrocephalus patients develop parkinsonism (rigidity and/or resting tremor in addition to bradykinesia and gait disturbance) [6, 7]. In some cases, especially those in which acute
123
Neurol Sci
hydrocephalus develops due to shunt obstruction, levodopa has a dramatic effect [6, 8]. The physiopathology might involve reversible dysfunction of the presynaptic nigrostriatal dopaminergic pathway adjacent to the expanded third ventricle [6]. The absence of a response to levodopa in our patient suggests that the not only nigrostriatal system but also other basal ganglia circuits, including the striatum and its projections to motor and/or supplemental motor areas in the frontal lobe, were dysfunctional [6]. In conclusion, we have described the first case of parkinsonism associated with RM, presumably caused by secondary hydrocephalus. Additional reports of similar cases would help to elucidate the clinical features and pathogenesis of this condition and to develop effective therapeutic strategies. Acknowledgments We are very grateful to Dr. Merle Ruberg for critical reading of this manuscript. Conflict of interest interest.
The authors declare that there is no conflict of
References 1. Bathon JM, Moreland LW, DiBartolomeo AG (1989) Inflammatory central nervous system involvement in rheumatoid arthritis. Semin Arthr Rheum 18:258–266 2. Kato T, Hoshi K, Sekijima Y et al (2003) Rheumatoid meningitis: an autopsy report and review of the literature. Clin Rheumatol 22:475–480 3. Shimada K, Matsui T, Kawakami M et al (2009) Diffuse chronic leptomeningitis with seropositive rheumatoid arthritis: report of a case successfully treated as rheumatoid leptomeningitis. Mod Rheumatol 19:556–562 4. Hasiloglu ZI, Asik M, Erer B, Eikici AS, Altintas A, Albayram S (2012) Magnetic resonance imaging of rheumatoid meningitis: a case report and literature review. Rheumatol Int 32:3679–3681 5. Hildebrand J, Aoun M (2003) Chronic meningitis: still a diagnostic challenge. J Neurol 250:653–660 6. Curran T, Lang AE (1994) Parkinsonian syndromes associated with hydrocephalus: case reports, a review of the literature, and pathophysiological hypotheses. Mov Disord 9:508–520 7. Krauss JK, Regal JP, Droste DW, Orszagh M, Borremans JJ, Vach W (1997) Movement disorder in adult hydrocephalus. Mov Disord 12:53–60 8. Kim MJ, Chung SJ, Sung YH, Lee MC, Im JH (2006) Levodoparesponsive parkinsonism associated with hydrocephalus. Mov Disord 21:1279–1281
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