IgG4-Related Disease Complicated by Brain Parenchymal Lesions Successfully Treated with Corticosteroid Therapy: A Case Report.

Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is distinguished by the infiltration of IgG4-positive plasma cells in a variety of tissues and organs including the pancreas, salivary glands, retroperitoneal lesions, kidney, and lymph nodes with elevated serum IgG4 levels. Even so, central nervous system (CNS) lesions such as brain parenchymal lesions associated with IgG4-RD are scarce. So far, only six cases of IgG4-RD in relation with brain parenchymal lesions have been described, with its characteristics still being not clear. Here we have detailed a case of IgG4-RD with brain parenchymal lesions and reviewed previously-reported cases of IgG4-RD with brain parenchymal lesions. A 62-year-old Japanese male suffering from lung silicosis was admitted to our hospital for abdominal discomfort and altered consciousness. He has shown no major neurologic abnormalities except for drowsiness, urinary retention, and fecal incontinence. Brain magnetic resonance imaging has shown scattered hyperintense signals in the brain parenchyma. The serum IgG4 levels were elevated and systemic lymph nodes were enlarged. Biopsy from inguinal lymph nodes has shown massive infiltration of IgG4-positive plasma cells: the ratio of IgG4-positive/IgG-positive plasma cells was nearly 100%. Based on clinical courses, images, laboratory data, and pathological findings, a diagnosis of IgG4-RD that was complicated by brain parenchymal lesions and sacral nerve disturbance was confirmed. The patient was then given methylprednisolone pulse therapy (1g for 3 days) succeeding oral prednisolone (1 mg per body weight). The clinical and radiological improvements together with steroid therapy proposed IgG4-RD to be the cause of the lesions.

Charcot-Marie-Tooth disease type 4C in Japan: report of a case.

INTRODUCTION: The distribution of documented cases of Charcot-Marie-Tooth disease type 4C (CMT4C) is mainly limited to the Mediterranean region. We report the first documented case of CMT4C in East Asia. Furthermore, we estimate the proportion of CMT4C in Japan and compare the same with that in European countries. CASE REPORT: A 72-year-old Japanese woman presented with early-onset motor and sensory neuropathy associated with scoliosis, deformities of the hands and feet, and carpal tunnel syndrome. A genetic screen detected a homozygous p.R529Q mutation in SH3TC2, the causative gene of CMT4C. The SH3TC2 mutation identified here is unique among 426 unrelated Japanese CMT patients, excluding those with CMT1A. CONCLUSIONS: Although CMT4C also occurs in Japan, it is less common than in European countries.

Analysis of J waves during myocardial ischaemia.

AIMS: The aim of this study was to investigate the relationship between J-wave dynamics and arrhythmias during myocardial ischaemia in patients with vasospastic angina (VSA). METHODS AND RESULTS: Sixty-seven consecutive patients diagnosed with VSA by a provocation test for coronary spasm were grouped according to whether they had a J wave in the baseline electrocardiograms or not (VSA-JW group, n = 14; VSA-non-JW group: n = 53). We retrospectively studied the associations between J-wave and ST-segment dynamics and induced ventricular fibrillations (VFs) during coronary spasm.  In the VSA-JW group, 7 of the 14 patients showed changes in J-wave morphology and/or gains in J-wave voltage, followed by VF in 4 patients. Compared with patients without VF, the four patients with VF showed similar maximal voltage in the baseline J waves but a higher voltage during induced coronary spasms (0.57 ± 0.49 vs. 0.30 ± 0.11 mV; P = 0.011). In three patients with VF, J waves progressively increased and were accompanied by the characteristic coved-type or lambda-shaped ST-segment elevations. In the VSA-non-JW group, only four patients showed new appearances of J waves during coronary spasms and another patient without a distinct J wave developed VF. Ventricular fibrillations were induced more frequently in the VSA-JW group than in the VSA-non-JW group [4/14 (29%) vs. 1/53 (2%); P = 0.012]. CONCLUSION: J-wave augmentations were caused by myocardial ischaemia during coronary spasms. The presence and augmentation of J waves, especially prominent J waves with the characteristic ST-elevation patterns, were associated with VF.

Nephrotic Syndrome and Atypical Posterior Reversible Encephalopathy Syndrome in a Patient with Parkinson's Disease.

A 59-year-old man with advanced Parkinson's disease treated using levodopa-carbidopa intestinal gel (LCIG) presented with leg edema, hypoalbuminemia, and proteinuria at 1 year after the treatment. He subsequently developed a generalized tonic-clonic seizure, and brain magnetic resonance imaging indicated vasogenic edema in the white matter of the left frontal subcortex. He was diagnosed with nephrotic syndrome (NS) and atypical posterior reversible encephalopathy syndrome (PRES). LCIG cessation and corticosteroid treatment improved the NS. To our knowledge, this is the first case report of NS and atypical PRES in patients with Parkinson's disease. Patients being treated with LCIG should be closely monitored for NS.

Efficacy and safety of bosentan treatment for portopulmonary hypertension associated with syncope.

Pulmonary arterial hypertension (PAH) in patients with portal hypertension is also referred to as portopulmonary hypertension (PPHTN). Here, we report a case of PPHTN caused by alcoholic liver cirrhosis in a 43-year-old male who experienced repetitive syncope on exertion. The continuous monitoring of pulmonary artery pressure and radial artery pressure revealed that his PAH was aggravated with a drop in systemic arterial pressure during an exercise test. Bosentan, an endothelin A/B receptor antagonist, improved the patient's hemodynamic parameters and abolished his syncope without adverse effects. This is the first report that bosentan may be effective and safe for PPHTN associated with syncope.

Locomotion outcome in hemiplegic patients with middle cerebral artery infarction: the difference between right- and left-sided lesions.

OBJECTIVE: This study was performed to analyze the locomotion outcome of hemiplegic patients with stroke and to explore the factors influencing it. METHODS: A total of 247 patients (mean age 65.6 +/- 10.5 years) admitted to our hospital for rehabilitation were included in the study. Their cardinal neurologic sign was hemiplegia caused by infarction in the middle cerebral artery as a result of a first stroke. When rehabilitation programs were completed, the final motor outcome was evaluated and compared between patients with right and left hemispheric infarct. In addition, the following items were analyzed: size, location, and subtype of the infarct; hemispatial neglect and aphasia; cerebral blood flow (CBF); and periventricular lucency on computed tomography scan. RESULTS: (1) There was a negative relationship between the infarct size and the locomotion outcome. The difference in locomotion outcome was not significant between the patients with infarction of the perforating arteries and those of the cortical arteries. No significant difference in the locomotion outcome was found between the patients with an atherothrombotic or cardioembolic infarction. (2) In spite of the existence of hemispatial neglect or aphasia, the patients with a right-sided infarction were significantly inferior to patients with a left-sided one in locomotion outcome, except for those with a large infarction. (3) In patients with infarction in the territory of the perforating arteries, there was a negative relationship between the area of decreased CBF or periventricular lucency and the locomotion outcome. When the area of decreased CBF on the homolateral hemisphere involving the infarction extended to less than or equal to two cerebral lobes, the locomotion outcome was significantly worse in the patients with a right-sided infarction. CONCLUSIONS: Overall, for the patients with middle cerebral artery infarction, the locomotion outcome was poorer in patients with a right hemispheric infarction than a left-sided one, except in the case of a large infarction.

[A case of leptomeningeal melanomatosis with acute paraplegia and multiple cranial nerve palsies].

A 62-year-old man with acute paraplegia was transferred to our hospital. He had flaccid paraplegia and multiple cranial nerve palsies, such as mydriasis of the left pupil, abduction palsy of the left eye, hoarseness and dysphagia, but no meningeal irritation signs. MRI of the spinal canal showed swellings of the conus medullaris and the cauda equine, and also contrast enhancement of the spinal meninges. The cerebrospinal fluid (CSF) showed pleocytosis and protein increment. The lymph node was swollen in his right axilla. The biopsy specimen from the right axillary lymph node revealed metastasis of malignant melanoma histologically. Careful check-up of his whole body found a malignant melanoma in the subungual region of the right ring finger. Repeated cytological examination revealed melanoma cells in the CSF, confirming the diagnosis of leptomeningeal melanomatosis. His consciousness was gradually deteriorated. His family members chose supportive care instead of chemotherapy or surgical therapy after full information about his conditions. Finally, he died 60 days after transfer to our hospital. This is a rare case of leptomenigeal melanomatosis presenting with acute paraplegia and multiple cranial nerve palsies. Careful follow-up and repeated studies are vital for the early diagnosis of leptomenigeal melanomatosis in spite of atypical clinical presentation.

Vasodilatation of multiple cerebral arteries in early stage of stroke-like episode with MELAS.

We describe a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), with multiple cerebral vasodilatations in a stroke-like episode visualised by using magnetic resonance angiography (MRA) and CT angiography (CTA). In the acute stroke-like episode stage, T2-weighted and fluid-attenuated inversion recovery MRI showed high-intensity areas in the left occipital area. In addition, MRA and CTA revealed prominent dilatation of the left posterior cerebral artery and temporal branches of the middle cerebral artery with focal hyperperfusions using CT perfusion (CTP) that corresponded to the MRI. After 10 days, with the development of aphasia, MRI indicated the lesions had spread to the temporal and parietal regions, and this distribution was not confined to major vascular territories. The patient's symptoms gradually improved, accompanied by the attenuation of MRI, CTA, and CTP findings. These characteristic features along with the MRI changes that spread beyond vascular boundaries and the multiple cerebral vasodilatations prior to the development of clinical symptoms are not fully explained by the mitochondrial angiopathy or cytopathy theories. These findings provide further evidence supporting neuronal hyperexcitability in stroke-like episodes of MELAS.

Neuroradiologic and clinical abnormalities in dementia of diffuse neurofibrillary tangles with calcification (Kosaka-Shibayama disease).

We describe a characteristic dementia patient diagnosed as diffuse neurofibrillary tangles with calcification (DNTC). Neuropsychologically, dementia, including a decline in memory retention and intelligence, and anomic aphasia were recognized. Imaging revealed circumscribed temporal dominant atrophy and calcification of the basal ganglia and cerebellum. SPECT and FDG-PET revealed a remarkable reduction of blood flow and metabolism in the temporal lobes; however, there is no reduction in the basal ganglia and cerebellum, and FDOPA-PET also disclosed no abnormalities. This suggests that calcification and neuronal degeneration occur independently in DNTC.

Hemodynamic basis of the reduced oxygen uptake relative to work rate during incremental exercise in patients with chronic heart failure.

BACKGROUND: The ratio of the increase in oxygen uptake to the increase in work rate (DeltaVO2/DeltaWR) during incremental exercise is reduced in patients with severe chronic heart failure (CHF). However, the pathophysiological basis of the reduced O2 uptake relative to work rate has not been elucidated. METHODS: To elucidate the hemodynamic basis of the reduced ratio of DeltaVO2/DeltaWR during exercise in severe CHF, 48 patients with CHF (15 patients in class I, 21 in class II and 12 in class III) performed maximal ergometer exercise with respiratory gas analysis. Cardiac output and systemic O2 extraction were measured at 1-min intervals during exercise. RESULTS: Both peak VO2 and peak cardiac output decreased as the severity of CHF advanced. Patients in class III showed significantly reduced DeltaVO2/DeltaWR than those in class I (8.2+/-0.9 vs. 9.8+/-1.5 ml/min/W, P<0.01). Cardiac output at rest was significantly lower, and O2 extraction at rest was significantly higher in class III than class I. The ratio of the increase in cardiac output to the increase in work rate (DeltaCO/DeltaWR) was significantly lower in class III than class I (42.5+/-14.5 vs. 60.6+/-10.3 ml/min/W), and the ratio of the increase in O2 extraction to the increase in work rate (DeltaO2 extraction/DeltaWR) was significantly higher in class III than class I (0.45+/-0.13 vs. 0.34+/-0.08%/W). The DeltaVO2/DeltaWR was significantly correlated with the DeltaCO/DeltaWR (r=0.67, P<0.01), and the DeltaCO/DeltaWR was inversely correlated with DeltaO2 extraction/DeltaWR (r=-0.65, P<0.01). CONCLUSIONS: Decreased O2 supply due to reduced cardiac output was not fully compensated by the increased O2 extraction. Reduced ratio of DeltaVO2/DeltaWR in advanced CHF reflected the severely attenuated cardiac output response to exercise.

Ticlopidine alone versus ticlopidine plus aspirin for preventing recurrent stroke.

OBJECTIVE: To compare the efficacy and safety of two antiplatelet regimens, ticlopidine alone (200 mg daily) and ticlopidine (100 mg daily) plus aspirin (81 mg daily), in patients with ischemic stroke from the Tokai district of Japan. METHODS: A randomized comparative study was performed from April 1992 until December 1995, with follow-up for an average of 1.59 years (maximum: 3 years). Statistical analysis was done on 270 eligible patients (138 treated with ticlopidine alone and 132 treated with ticlopidine plus aspirin). PATIENTS: A total of 276 patients who had cerebral infarction within the previous 1 to 6 months, or one or more transient ischemic attacks within the previous 3 months. RESULTS: The incidence of ischemic and hemorrhagic stroke, myocardial infarction, and other vascular events was 10.1% (n = 14) in the ticlopidine group and 9.8% (n = 13) in the ticlopidine plus aspirin group, showing no significant difference (p = 0.933). There was also no significant difference in the event-free rate between the two groups (p = 0.5003, Kaplan-Meier analysis and log-rank test). Regarding serious adverse reactions, neutropenia occurred in one patient from the ticlopidine group, while gastric ulcer and thrombocytopenia occurred in one patient each from the ticlopidine plus aspirin group. CONCLUSION: We conclude that both antiplatelet regimens are comparable in efficacy and safety for preventing the recurrence of ischemic stroke.

Post-exercise exhaustion in Lambert-Eaton myasthenic syndrome.

OBJECTIVES: To study post-exercise exhaustion by decrement (PEE-D) systematically in 24 repetitive nerve stimulation (RNS) tests in 14 patients with Lambert-Eaton myasthenic syndrome (LEMS). METHODS: In the abductor digiti quinti muscle, the compound muscle action potential (CMAP) amplitude and 3Hz responses for 2s were obtained with the supramaximal stimulation at rest, immediately after (PE0), 30s after (PE30s), and at 1, 2, 3, and 4m after 10-s exercise. RESULTS: There was a 377% increment in the CMAP amplitude at PE0 and a mild increment (+26%) at PE30s. A transient but significant improvement (-22%) in the decremental response was observed at PE0, and a gradual worsening of decrement in subsequent tests, with the worst decrement noted (-50%) at PE2m. CONCLUSION: PEE-D was found 2m after exercise in LEMS. SIGNIFICANCE: PEE-D may be physiologically closest to the reversible myasthenic fatigue after exercise observed in LEMS patients.

Can palm stimulation differentiate diabetic polyneuropathy from carpal tunnel syndrome?

PURPOSE: Diabetic patients without symptoms of carpal tunnel syndrome (CTS) may frequently show a prolongation of their median distal latency. Previous authors have reported that diabetic polyneuropathy (DPN) and CTS were differentiated by evaluating the sensory conduction velocity (SCV) distal to the palm. This study aimed to clarify this issue. METHODS: The subjects consisted of 30 DPN patients without clinical CTS and 50 CTS patients without diabetes mellitus. An antidromic sensory conduction study stimulating the median nerve at the wrist and palm was performed. The SCV distal to the palm (SCVpf) and across the carpal tunnel (SCVwp) and the sensory nerve action potential amplitude following palmar stimulation (AMP-p) were evaluated. RESULTS: The SCVwp was significantly lower than the SCVpf in DPN patients, implying the frequent presence of subclinical lesion at the carpal tunnel. The SCVpf was similar for both groups. The AMP-p was disproportionately low in relation to SCVwp in DPN patients, as compared with CTS patients. CONCLUSIONS: The polyneuropathic feature of DPN is primarily expressed as axonal loss. The diabetic axonal loss index has been introduced, which enabled to determine the co-presence, isolated presence, or absence of DPN/CTS in the electrophysiological sense.

The importance of medical interview with CKD patient in diagnoses of a family with Fabry disease.

A 47-year-old Japanese man was admitted to our hospital for evaluation of proteinuria, which was detected when he was 37 years of age. His creatinine clearance levels had fallen to 76.3 mL/min/1.73 m2. A kidney biopsy was conducted, and the patient's low plasma α-galactosidase A levels suggested Fabry disease. After genetic counseling, GLA analysis revealed a novel mutation p.L387P. Interview with the patient revealed that both his younger brother and mother suffered from cardiomyopathy and were undergoing cardiological treatment. They also were positive for proteinuria. About 30 years ago, the patient's cousin (aged 25) was diagnosed with Fabry disease. He underwent hemodialysis for 9 years until his death at 42. At that time, the patient and his brother had not been investigated for Fabry disease so their cousin could not act as a proband for the brothers. Eventually, the patient, his mother, and his brother were put on enzyme replacement therapy with agalsidase beta. As this series of cases shows, medical interviews to collate both medical and family history were essential for the discovery of Fabry disease in these patients. In addition, being a treatable genetic disorder, Fabry disease should be listed in the standard differential diagnoses of systemic and familial diseases, including unknown cause of nephropathy or cardiomyopathy, for early detection of the disorder.

[A case of subacute parkinsonism presenting as bilateral basal ganglia legions by MRI in diabetic uremic syndrome].

A 60-year-old male was admitted because he had developed tremulous movement in both upper and lower limbs and gait disturbance over the course of 3 months. He had been on continuous ambulatory peritoneal dialysis almost 1 year earlier due to end-stage diabetic nephropathy. A neurological examination revealed a mild disturbance of his consciousness, asterixis in the upper limbs, bilateral extensor plantar responses and parkinsonism, which were characterized by bradykinesia, akinesia, rigidity, and bilaterally tremors at rest. Cranial magnetic resonance imaging (MRI) revealed swollen bilateral basal ganglia legions, which appeared hyperintense on T2-weighted images. The patient was treated for metabolic acidosis and continued hemodialysis three times a week; however, the parkinsonism remained 1 year later. Follow-up MRI revealed decreased swelling of the basal ganglia, and the pattern of diffusion-weighted images and the apparent diffusion coefficient (ADC) map indicated vasogenic and cytotoxic edema in bilateral globus pallidus. The case was diagnosed as encephalopathy due to diabetic uremic syndrome, initially characterized by Wang et al. (2003). Only 17 cases with parkinsonism have been reported. Diabetic uremic syndrome is characterized by acute or subacute onset consciousness disturbance and movement disorders such as parkinsonism, chorea and the other extrapyramidal signs to various degrees related to bilateral lesions of the basal ganglia.

Simultaneous development of acute disseminated encephalomyelitis and Guillain-Barré syndrome associated with H1N1 09 influenza vaccination.

A 36-year-old man was admitted to our hospital because of urinary retention and muscle weakness affecting all 4 limbs after receiving a H1N1 09 influenza vaccination. Magnetic resonance imaging demonstrated multiple lesions in his brain and spinal cord. Furthermore, nerve conduction study showed acute sensorimotor neuropathy, and anti-GM2 antibodies were detected in his serum. Based on the temporal association and exclusion of alternative etiologies, we made a diagnosis of acute disseminated encephalomyelitis (ADEM) and Guillain-Barré syndrome (GBS). To our knowledge, this is the first case of co-morbid ADEM and GBS after influenza vaccination with positive anti-ganglioside antibodies.

Extreme efficacy of intravenous immunoglobulin therapy for severe burning pain in a patient with small fiber neuropathy associated with primary Sjögren's syndrome.

Neurological involvement occurs in approximately 20% of patients with primary Sjögren's syndrome. Although neurological symptoms can affect the peripheral nervous system and the central nervous system, the most frequent symptom is polyneuropathy. Small fiber neuropathy (SFN) is a form of painful peripheral polyneuropathy that is common in patients with diabetic neuropathy, but may also occur in toxic, infectious, or immune-mediated neuropathy. We show here a patient with Sjögren's syndrome who developed SFN and was treated with intravenous immunoglobulin (IVIG) therapy, which was immediately and extremely effective. Because of the efficacy of IVIG therapy, we propose that direct immune-mediated mechanisms may be involved in the pathogenesis of SFN complicated by Sjögren's syndrome.

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome accompanied by Parkinson's disease.

We encountered two cases of RS3PE (remitting seronegative symmetrical synovitis with pitting edema) syndrome accompanied by Parkinson's disease (PD). Although the etiology of RS3PE syndrome is still unknown, several possible associations, such as malignancies and viral infections, have been reported; RS3PE syndrome is thought to be an autoimmune-mediated disorder. The present patients did not have any factors which are reported to be associated with RS3PE. Whether or not the complication of PD and RS3PE syndrome is incidental needs to be further examined, and we discuss here the possible cause of association between PD and RS3PE syndrome, including dopamine agonists one of the anti-PD medications.