Among varying organ involvements, neurologic as well as musculoskeletal involvement are important toward the quality of life and prognosis in the patients of rheumatic diseases. In general, these occur as the increment of disease activity and influence the choice of therapeutic regime. In this review, neurologic and musculoskeletal involvements, especially the former, found in systemic lupus erythematosus, dermatomyositis/polymyositis, Sjögren’s syndrome, Behçet’s disease and vasculitis syndrome are discussed.
A 49-year-old female neuromyelitis optica spectrum disorder (NMOSD) patient with positive anti-aquaporin 4 (AQP4) antibody was treated with fingolimod (FTY720). Ten days later, she developed acute disturbance of consciousness, aphasia, right hemi-spatial neglect, and right hemiparesis. Brain MRI showed multiple white-matter lesions with slight Gadolinium enhancement. She was diagnosed of acute exacerbation of NMOSD. Thus, fingolimod may be associated with the development of a fulminant course in NMOSD patients with positive anti-AQP4 antibody
About three weeks after successful coil embolization of a basilar apex aneurysm, a 66-year-old woman developed occipital headaches. T2 and FLAIR MRI brain images demonstrated multiple new hyperintense lesions in the posterior circulation territory including cerebellum, right superior cerebellar peduncle, left thalamus and bilateral temporo-occipital lobes and she was subsequently hospitalized. Findings suggestive of other underlying disease were not observed, although an increased protein level was noted in cerebrospinal fluid (69 mg/dl). Headache and clinical findings improved approximately 12 weeks after coil embolization. MRI findings also showed improvement. These clinical and radiological findings made this patient a distinctive case of posterior reversible encephalopathy syndrome (PRES) associated with coil embolization suggesting that clinicians should be aware that PRES can present as comparatively mild symptoms several weeks after coil embolization.
A 60-year-old man was admitted to our hospital because of fever and mental status change. Neurological examination showed meningeal irritation and frontal sign. Cerebrospinal fluid (CSF) examination showed mild pleocytosis and elevated protein. Laboratory findings showed hyponatremia, elevated liver enzymes and creatine phosphokinase, and positive Legionella pneumophila antigen in urine. The chest computed tomographic scans showed consolidation in the left lower lobe lung. We diagnosed Legionnaires’ pneumonia and started treatment with levofloxacin. Legionella pneumophila was isolated from culture of the bronchoalveolar lavage fluid, but Legionella culture and polymerase chain reaction in CSF were negative. We hypothesize that Legionella pneumophila could produce nerological symptoms by immune-mediated mechanism associated with elevated IgG index. The neurologist should recognize the presence of the meningo-encephalitis associated with Legionnaires’ pneumonia lacking remarkable pulmonary symptoms.
A 40-year-old man who presented with left hemiparesis was admitted to our hospital. He had tachycardia and a fever. He had a 25-year history of insulin therapy for diabetes mellitus. Brain magnetic resonance (MR) images showed fresh infarction in the right hemisphere, and carotid ultrasonography showed stenosis of the right internal carotid artery (ICA). We determined that atherothrombotic brain infarction had likely occurred. After admission, the right ICA became narrow and finally occluded. Computed tomography revealed the presence of a thrombus in the right ICA, and gadolinium-enhanced MRA showed vasculitis of the ICA. In laboratory tests, his thyroid hormones were elevated. He was diagnosed with hyperthyroidism. After treatment, the tachycardia and high fever were improved. Because of a positive anti-glutamic acid decarboxylase antibody test result, he was diagnosed with insulin-dependent diabetes mellitus. We found that he had anti-phospholipid antibody syndrome because he was positive for anti-beta-glycoprotein I antibody. These findings suggested that his condition was autoimmune polyglandular syndrome type 3. He received prednisolone and warfarin. After 3 months, his neurological findings were improved; however, occlusion of the ICA remained. Autoimmunity was considered to be the cause of ICA occlusion. Ischemic stroke with autoimmune polyglandular syndrome is very rare and is associated with progressive carotid lesions in juvenile patients. It is necessary to diagnose and treat this condition as soon as possible.
Intramedullary spinal cord hemorrhage (hematomyelia) is rare and usually related to trauma. Spinal vascular malformations such as intramedullary cavernomas and intradural arteriovenous malformations are the most common cause of atraumatic hematomyelia. Other considerations include warfarin or heparin anticoagulation, bleeding disorders, spinal cord tumors, and delayed complication of spinal radiation. We report the case of 48-year-old man receiving warfarin and aspirin therapy, who showed upper limb pain and dysesthesia from left axilla to left femur. Paraplegia, sensory disturbance, bladder and rectal disturbance developed gradually over two weeks, accompanied by severe back and neck pain. MRI showed hematomyelia extending from the C1 to T11 segments of the spinal cord. The hemorrhage was located mainly in the left side of the posterior column. Few cases of hematomyelia extending over 18 segments of the spinal cord have been reported. Past literature reports of hematomyelia tend to extend longitudinally above and below the area of initial hemorrhage. We thought that the shape of this hematomyelia extending longitudinally over several segments was formed by a similar pathogenesis to pencil-shaped softening of the spinal cord.
A 37-year-old man was admitted to our hospital because of progressive abnormal gait and severe pain in the low back and lower extremities, more severe on the right side, especially in his right posterior thigh. The pain appeared one week after he suffered from slight fever and diarrhea. On admission, a neurological examination revealed mild distal weakness of the all extremities and loss of Achilles tendon reflex, associated with positive Lasègue sign. However, sensation was intact except for slightly impaired vibratory sensation on the trunk. An electrophysiological study showed diminished amplitude of compound muscle action potential and loss of F-wave of the posterior tibial nerves. Finding of cerebrospinal fluid was normal at the time of admission, although 12 days later albuminocytologic dissociation was found. Cervical and lumbar magnetic resonance images showed gadolinium enhancement of the anterior nerve roots and the cauda equina, more prominent on the right side, correlating with the prominent side of the patient’s leg pain. Because of neurological features, electrophysiological abnormalities and CSF findings, we diagnosed his illness as Guillain-Barré syndrome (GBS) characterized by severe back and leg pain. The character of pain was deep and aching, suggesting myalgic pain caused by the affected anterior roots. A short course high-dose intravenous immunoglobulin (IVIg) therapy was not effective against the radicular pain although minimal improvement of limb weakness occurred. Non-steroidal anti-inflammatory drugs and carbamazepine were unsuccessful for pain relief. Thereafter, intravenous methylprednisolone (IVMP) pulse therapy was introduced. On the day IVMP pulse therapy started, severe radicular pain began to decrease and became gradually milder without any marked effect on the other symptoms and signs of GBS. Moderate to severe pain is a common and early symptom of GBS and requires aggressive treatment. IVMP pulse therapy may be one of treatments for refractory and intolerable pain of GBS.
A 60-year-old woman was admitted to our hospital because of difficulty in standing on her toes. Neurological examination showed muscle weakness in both calf muscles. Her serum creatine kinase (CK) level was slightly elevated. MRI revealed hyper-intense signals localized in both the gastrocnemius and soleus muscles. Histological examinations of biopsied muscle specimens showed a marked variation in fiber size, small angular fibers, and hypertrophic and splitting fibers, but no muscle fiber necrosis or regeneration or inflammatory cell infiltration. ATPase stained sections showed small grouped atrophy of type 1 fibers. NADH-TR stained sections showed target/targetoid fibers predominantly in type 1 fibers. Dysferlin immunoreactivity was normal. Follow-up clinical evaluation for one year showed no progression. This patient was diagnosed as having an unknown type of spinal muscular atrophy or benign calf amyotrophy. Sporadic cases characterized by elderly-onset, neurogenic muscular atrophy localized in both calf muscles, and non-progressive course are extremely rare in Japan.
An 18-year-old woman was admitted because of sore throat and pain in the epigastric region. On admission, she presented with swollen tonsils and hepatosplenomegaly. Blood examinations revealed the presence of atypical lymphocytes, liver damage and anti-VCA IgM and IgG antibodies. These findings led to diagnosis of infectious mononucleosis. After admission, her condition improved, but on hospital day 4, she suddenly developed cerebellar ataxia in the trunk and four limbs. Cranial MRI findings were normal. Cerebrospinal fluid (CSF) collected on hospital day 6 showed normal cell counts and normal concentrations of protein and glucose. EB virus DNA and anti-VCA IgM and IgG antibodies were negative and glutamate receptor δ2 antibody was positive in CSF collected on hospital day 11. We diagnosed acute cerebellar ataxia (ACA) and performed methylprednisolone pulse therapy. After this therapy, her cerebellar ataxia improved over a few days. This is the first reported case of ACA after EB virus infection presenting with glutamate receptor δ2 antibody in CSF. The glutamate receptor δ2 subunit is expressed on cerebellar Purkinje cells. Therefore, the presence of the antibody may be associated with cerebellar dysfunction. In the present case, secondary immune reactions after EB virus infection may have produced the antibody.
We report the case of a 65-year-old woman who presented with Churg-Strauss syndrome (CSS) associated with multiple cerebral infarcts. Four years ago, she was diagnosed as having CSS based on asthma, hypereosinophilia and peripheral neuropathy, and corticosteroid therapy achieved a remission. However, she showed exacerbation of asthma and hypereosinophilia during the tapering schedule of steroid, and she was hospitalized because of dizziness and mild left side weakness. Analysis of blood chemistry detected significant hypereosinophilia (13,730/μl), increased blood-coagulating activity, elevated NT-proBNP concentration and renal dysfunction. MRI of the brain revealed multiple small infarcts in cortex and the watershed area. The patient was diagnosed with exacerbation of CSS, and treatment with increased dose of corticosteroid induced a clear improvement in symptoms, with decrease of the eosinophilia and a clear improvement of the renal function. The hypercoagulable state and direct eosinophil toxicity may contribute to strokes in hypereosinophilic condition of CSS. This case was remarkable for illustrating multiple cerebral infarctions in CSS. CSS should always be considered in patients with hypereosinophilia and stroke.