Optic neuropathy secondary to granulomatosis with polyangiitis in a patient with Graves' disease: a case report.

BACKGROUND: Dysthyroid optic neuropathy is the most commonly suspected diagnosis of optic neuropathy in Graves' patients; however, other causes need to be ruled out. We present a unique case of optic neuropathy secondary to hypertrophic pachymeningitis with antineutrophil cytoplasmic antibody-associated vasculitis, which was suspected to be antithyroid drug related. CASE PRESENTATION: A 79-year-old Japanese male presented with acute visual loss in the left eye. He had a 24-year history of Graves' disease and was taking methimazole. Best-corrected visual acuity was 0.8 in the right eye and light perception in the left eye, and relative afferent pupillary defect in the left eye was seen. Ocular movement was normal, and there were no findings explaining visual loss in intermediate optic media and fundus in the left eye. Contrast-enhanced magnetic resonance imaging demonstrated thickened dura mater. Tests for myeloperoxidase-antineutrophil cytoplasmic antibody, proteinuria, and hematuria were positive; pulmonary nodule lesions and a blood clot in the left lower leg were also found. After excluding the presence of diseases that could lead to hypertrophic pachymeningitis, we diagnosed optic neuropathy due to hypertrophic pachymeningitis with granulomatosis with polyangiitis-a subtype of antineutrophil cytoplasmic antibody-associated vasculitis. Since he had history of using methimazole, antineutrophil cytoplasmic antibody-associated vasculitis was considered as drug related. We started high-dosage steroid pulse therapy followed by 1 mg/kg body weight daily of oral prednisolone, and subsequently tapered. Methimazole was stopped. Best-corrected visual acuity recovered to 0.9, 2 weeks after starting treatment. Though myeloperoxidase-antineutrophil cytoplasmic antibody remained negative, the symptom relapsed 6 months after treatment initiation. We gave a second high-dose steroid pulse therapy followed by prednisolone tapered together with methotrexate. Remission remained, and using 4 mg/week methotrexate without prednisolone, myeloperoxidase-antineutrophil cytoplasmic antibody was kept within the normal limit until now, 4 years after onset. CONCLUSION: We present a case of optic neuropathy with hypertrophic pachymeningitis related to antineutrophil cytoplasmic antibody-associated vasculitis, which was suspected to be drug related. The patient had good visual recovery after quitting the drug and receiving immunosuppressive therapy with systemic steroids. Hypertrophic pachymeningitis with antineutrophil cytoplasmic antibody-associated vasculitis related to antithyroid drugs should be considered as a differential diagnosis for optic neuropathy in Graves' patients in whom optic nerve compression is not obvious.

Up-regulation of CX3CR1 on tonsillar CD8-positive cells in patients with IgA nephropathy.

Although tonsillectomy are used as therapeutic options to prevent chronic renal failure in IgA nephropathy (IgAN) patients, the relationship between IgAN and tonsils is not fully proved by basic research. Recently, circulating CX3CR1-positive cells were reportedly involved in promoting hematuria in patients with IgAN. In this study, we focused on the expression of CX3CR1 in tonsillar mononuclear cells in IgAN patients. Immunohistological analysis revealed greater distribution of CX3CR1-positive cells in the inter-follicular area of tonsils in IgAN patients than in non-IgAN patients. CX3CR1-positive cells were also found in the affected renal glomerulus of IgAN patients. Flow cytometric analysis revealed the expression of CX3CR1 on tonsillar CD8-positive cells to be significantly higher in IgAN patients. CpG-oligodeoxynucleotides enhanced the expression in IgAN patients. The chemotactic response of tonsillar mononuclear cells to fractalkine was significantly higher in IgAN patients. Expression of CX3CR1 on peripheral blood CD8-positive cells in IgAN patients was significantly higher, and decreased after tonsillectomy, along with the disappearance of hematuria. These results suggest that hyper-immune response to microbial DNA enhanced the expression of CX3CR1 on tonsillar CD8-positive cells in IgAN patients, followed by the migration of the cells to renal lesions via blood circulation, resulting in the development of hematuria.

Stimulation of denervated muscle promotes selective reinnervation, prevents synkinesis, and restores function.

OBJECTIVES/HYPOTHESIS: Previously, electrical stimulation of denervated canine laryngeal muscle was shown to promote reinnervation by native over foreign motoneurons. The goal of this study was to assess the effect of different stimulus paradigms on reinnervation quality and functional recovery. STUDY DESIGN: A prospective study of six canines over 8 to 20 months. METHODS: A clinical model of laryngeal paralysis was used, where recurrent laryngeal nerves of the animals were sectioned and ventilation compromised. The abductor, posterior cricoarytenoid (PCA) muscles were implanted bilaterally with electrodes from an implantable pulse generator. Animals were randomly assigned to three groups to assess the effect of different stimulus paradigms: 1) 40 pulses per second (pps) train, 2) 10 pps train, 3) no stimulation. Spontaneous vocal fold movement was measured endoscopically during hypercapnia. Exercise tolerance was measured on a treadmill using pulse oximetry. In the terminal session, electromyography (EMG) potentials were recorded during superior laryngeal nerve stimulation to index foreign reinnervation of the PCA by reflex glottic closure (RGC) motoneurons. RESULTS: After reinnervation started, nonstimulated and stimulated 40 pps animals displayed paradoxical closure of the glottis during hypercapnia and severely decreased exercise tolerance due to faulty reinnervation. In contrast, stimulated 10 pps animals displayed minimal paradoxical closure and normal exercise tolerance (12 minutes up to 8 mph). EMG findings in this group demonstrated significantly less PCA reinnervation by foreign RGC motoneurons. CONCLUSION: PCA stimulation with low frequency reduced synkinetic reinnervation by foreign RGC motoneurons. Paradoxical closure of the glottis with inspiration was reduced and exercise tolerance restored to normal.

Intra-arterial cisplatin with concomitant radiation for advanced hypopharyngeal cancer.

OBJECTIVES/HYPOTHESIS: The current study evaluated the efficacy of radiation and concomitant high-dose superselective intra-arterial cisplatin infusion (RADPLAT) for patients with advanced hypopharyngeal cancer. STUDY DESIGN: Retrospective, single-institutional study. METHODS: Between February 2004 and October 2010, 43 patients with T2N0 or worse cancer were given superselective intra-arterial infusions of cisplatin (100-mg/m(2) or 75-mg flat dose per week) with simultaneous intravenous infusions of thiosulfate to neutralize cisplatin toxicity and conventional external beam radiotherapy (60-66 Gy). RESULTS: In total, three, seven, 21, and 12 patients were diagnosed with stage II, III, IVA, and IVB cancer, respectively. During the median follow-up period of 34 months, the 3-year overall survival, disease-specific survival, and progression-free survival rates for all patients were 52.2%, 68.2%, and 56.1%, respectively. The 3-year local control and laryngoesophageal dysfunction-free survival rates were 81.6% and 49.4%, respectively. No patient died because of treatment toxicity. Among grade IV toxicity, cerebral infarction (n = 1) and laryngeal necrosis (n = 1) resulting in laryngectomy were observed. CONCLUSIONS: Despite being a single-institution experience, the results of the current study suggest that RADPLAT can achieve favorable survival rates and high rates of laryngeal preservation for patients with advanced hypopharyngeal cancers. Laryngoscope, 2012.

Bilateral motion restored to the paralyzed canine larynx with implantable stimulator.

OBJECTIVES/HYPOTHESIS: Bilateral stimulation of posterior cricoarytenoid (PCA) muscles offers a physiologic approach to restore ventilation to a normal level in case of bilateral laryngeal paralysis. The objective of this study was to evaluate the long-term efficacy and safety of a new generation stimulator in restoring ventilation and exercise tolerance. STUDY DESIGN: A prospective study of four canines over 8-20 months. METHODS: A Genesis XP stimulator and electrodes were implanted and recurrent laryngeal nerves were sectioned and repaired bilaterally. In bimonthly sessions, vocal fold movement resulted from PCA stimulation or induced hypercapnea, was measured endoscopically in the anesthetized animal. Exercise tolerance was measured on a treadmill and swallowing function was examined endoscopically and radiographically. RESULTS: During the denervation phase, there was minimal ventilatory compromise and near-normal exercise tolerance. PCA stimulation produced only nominal abduction. During the reinnervation phase, synkinetic reinnervation became significant, resulting in a narrowed passive airway and paradoxical glottic closure during hypercapnea. Animals were stridorous and could walk for only 1-2 minutes. Bilateral PCA stimulation increased glottal area, equaling that of a normally innervated animal. Exercise tolerance was also normal. The optimal stimulus paradigm for the synkinetically reinnervated larynx was not different from that for the innervated larynx. Stimulation remained efficacious over the study period. Lead integrity could be maintained by prevention of device migration. There was no evidence of aspiration. CONCLUSIONS: This study demonstrates that ventilatory compromise only occurs following faulty reinnervation. Bilateral PCA stimulation can restore ventilation and exercise tolerance completely without aspiration over the long term.

Rehabilitation of bilaterally paralyzed canine larynx with implantable stimulator.

OBJECTIVES/HYPOTHESIS: Bilateral stimulation of the posterior cricoarytenoid (PCA) muscles offers a physiologic approach to rehabilitate ventilation to a normal level in case of bilateral laryngeal paralysis. The objective was to evaluate the safety and efficacy of a new generation stimulator in restoring glottal opening, ventilation, and exercise tolerance. STUDY DESIGN: A prospective study in three canines over 6 to 17 months. METHODS: A Genesis XP stimulator and electrodes were surgically implanted, and the recurrent laryngeal nerves sectioned/repaired bilaterally. In bimonthly sessions, vocal fold movement was measured endoscopically in the anesthetized animal. The movement resulted from PCA stimulation or hypercapnea during spontaneous breathing. Exercise tolerance was measured on a treadmill using pulse oximetry and swallowing function examined by videofluoroscopy. RESULTS: During the denervation phase, there was minimal ventilatory compromise and near normal exercise tolerance with the device off (12 minutes, up to 8 mph). PCA stimulation produced only nominal abduction. During the reinnervation phase, synkinetic reinnervation became significant with narrowed passive airway and paradoxical closure of the glottis during hypercapnea. Animals were stridorous and could walk for only 1 to 2 minutes at 4 mph. With the device activated, bilateral PCA stimulation increased glottal area from 50 mm(2) to 250 mm(2), even during hypercapnea, equaling that of a normally innervated animal. Exercise tolerance was normal. There was no evidence of aspiration during deglutition. CONCLUSIONS: This study demonstrates that severe ventilatory compromise only occurs following faulty reinnervation of laryngeal muscles. Bilateral PCA stimulation can result in complete rehabilitation of ventilation and exercise tolerance without impairment of swallowing.