Antibodies to the α3 subunit of the ganglionic-type nicotinic acetylcholine receptors in patients with autoimmune encephalitis.

Since autonomic dysfunction is closely associated with autoimmune encephalitis (AE), the objective of this study was to determine the autonomic symptoms and the prevalence of anti-α3 subunit of the ganglionic-type nicotinic acetylcholine receptor (gAChRα3) antibodies in the patients with AE. We reviewed the clinical features of 19 AE patients, and specifically analyzed sera for anti-gAChRα3 antibodies using the luciferase immunoprecipitation system (LIPS) assay. Cardiovascular autonomic symptoms were found to be common in patients with AE, and hypersalivation was seen only in patients with NMDAR encephalitis. LIPS detected anti-gAChRα3 antibodies in the sera from patients with AE (5/29, 26%). This study is the first to demonstrate that clinical characteristics including autonomic symptoms of AE patients with seropositivity for gAChR autoantibodies. It will be important to verify the role of gAChR antibodies in autonomic dysfunction and brain symptoms to clarify the pathogenesis of AE.

Clinical efficacy of haematopoietic stem cell transplantation for adult adrenoleukodystrophy.

Accumulated experience supports the efficacy of allogenic haematopoietic stem cell transplantation in arresting the progression of childhood-onset cerebral form of adrenoleukodystrophy in early stages. For adulthood-onset cerebral form of adrenoleukodystrophy, however, there have been only a few reports on haematopoietic stem cell transplantation and the clinical efficacy and safety of that for adulthood-onset cerebral form of adrenoleukodystrophy remain to be established. To evaluate the clinical efficacy and safety of haematopoietic stem cell transplantation, we conducted haematopoietic stem cell transplantation on 12 patients with adolescent-/adult-onset cerebral form/cerebello-brainstem form of adrenoleukodystrophy in a single-institution-based prospective study. Through careful prospective follow-up of 45 male adrenoleukodystrophy patients, we aimed to enrol patients with adolescent-/adult-onset cerebral form/cerebello-brainstem form of adrenoleukodystrophy at early stages. Indications for haematopoietic stem cell transplantation included cerebral form of adrenoleukodystrophy or cerebello-brainstem form of adrenoleukodystrophy with Loes scores up to 13, the presence of progressively enlarging white matter lesions and/or lesions with gadolinium enhancement on brain MRI. Clinical outcomes of haematopoietic stem cell transplantation were evaluated by the survival rate as well as by serial evaluation of clinical rating scale scores and neurological and MRI findings. Clinical courses of eight patients who did not undergo haematopoietic stem cell transplantation were also evaluated for comparison of the survival rate. All the patients who underwent haematopoietic stem cell transplantation survived to date with a median follow-up period of 28.6 months (4.2-125.3 months) without fatality. Neurological findings attributable to cerebral/cerebellar/brainstem lesions became stable or partially improved in all the patients. Gadolinium-enhanced brain lesions disappeared or became obscure within 3.5 months and the white matter lesions of MRI became stable or small. The median Loes scores before haematopoietic stem cell transplantation and at the last follow-up visit were 6.0 and 5.25, respectively. Of the eight patients who did not undergo haematopoietic stem cell transplantation, six patients died 69.1 months (median period; range 16.0-104.1 months) after the onset of the cerebral/cerebellar/brainstem lesions, confirming that the survival probability was significantly higher in patients with haematopoietic stem cell transplantation compared with that in patients without haematopoietic stem cell transplantation (P = 0.0089). The present study showed that haematopoietic stem cell transplantation was conducted safely and arrested the inflammatory demyelination in all the patients with adolescent-/adult-onset cerebral form/cerebello-brainstem form of adrenoleukodystrophy when haematopoietic stem cell transplantation was conducted in the early stages. Further studies are warranted to optimize the procedures of haematopoietic stem cell transplantation for adolescent-/adult-onset cerebral form/cerebello-brainstem form of adrenoleukodystrophy.

Hypoglossal Nerve Palsy as a Cause of Severe Dysphagia along with the Oropharyngeal Stenosis due to Occipitocervical Kyphosis.

Hypoglossal nerve palsy (HNP) is a potential cause of dysphagia. A 66-year-old man presented to our hospital with dysphagia and neck pain. One year prior to his first visit, he had been diagnosed with upper cervical tuberculosis and had undergone posterior C1-2 fixation. The physical examination led to the diagnosis of dysphagia with HNP, and he had severe weight loss. Radiographic examination revealed that the O-C kyphosis had been exacerbated and that the deformity was likely the primary cause of HNP. To restore the swallowing function, O-C fusion surgery was performed. Postoperatively, the patient showed immediate improvement of dysphagia with gradual recovery of hypoglossal nerve function. In the last follow-up evaluation, swallowing function was confirmed with no signs of HNP. Our results indicate that HNP could be more prevalent in cases with severe cervical kyphosis, being underdiagnosed due to the more apparent signs of the oropharyngeal narrowing.

Warfarin-related nephropathy in a patient with renal pelvic cancer.

An 83-year-old Japanese man had a history of chronic heart failure due to bradycardia-tachycardia syndrome. He was admitted to our hospital because of macrohematuria and acute kidney injury (AKI), which were detected by an urologist at an outpatient visit. He had a history of recurrent macrohematuria and transurethral resection of bladder tumors twice in the preceding 2 years. He had been on warfarin for 12 years, with a stable international normalized ratio (INR) that was usually less than 2.1. Urinalysis revealed numerous red blood cells (RBCs) and mild proteinuria without RBC casts. His serum creatinine level was elevated to 2.41 mg/dL from 0.96 mg/dL at 3 weeks before admission. INR was 1.44. Hydronephrosis was not observed. Ureteroscopy detected invasive urothelial carcinoma of the renal pelvis, and right laparoscopic nephroureterectomy was performed at 41 days after diagnosis of AKI. The background renal parenchyma displayed tubular obstruction by red blood cell casts and acute tubular injury, which were changes compatible with warfarin-related nephropathy (WRN). Warfarin was discontinued, and the serum creatinine level recovered to 1.66 mg/dL after 3 months. In the present patient with nephrosclerosis, WRN occurred at a therapeutic INR level after 12 years of uneventful warfarin therapy, and the coexisting urothelial malignancy was a unique feature.

Tacrolimus-Induced Reversible Cerebral Vasoconstriction Syndrome with Delayed Multi-Segmental Vasoconstriction.

Reversible cerebral vasoconstriction syndrome (RCVS) is a cerebrovascular syndrome characterized by multi-segmental constrictions of the cerebral arteries that resolves spontaneously within 3 months. Although RCVS is considered to be due to transient dysregulation of vascular tone, the exact pathomechanism remains unclear. We describe the case of a 15-year-old girl with RCVS induced by tacrolimus, who developed generalized seizure during the postoperative course of orthotropic heart transplantation. Magnetic resonance imaging at symptom onset showed a few vasoconstrictions accompanying brain edema and convexity subarachnoid hemorrhage. Although her neurological conditions rapidly improved after discontinuing tacrolimus, a repeat magnetic resonance angiogram demonstrated delayed progression of the multi-segmental vasoconstrictions followed by subsequent resolution. Our case demonstrates that cautious observation of the cerebral arteries using magnetic resonance angiography and careful management of vasoconstrictions with vasodilators are necessary for delayed vasoconstrictions even when the clinical symptoms improve.

Risk Factors Associated with Retinal Lesions Resulting from Widespread Systemic Infection.

PURPOSE: To clarify the prevalence, microbiologic features, and risk factors of endogenous intraocular infections in patients with positive fungal or bacterial blood culture results. DESIGN: Retrospective case series. PARTICIPANTS: Inpatients (n = 433) with positive blood culture results who underwent an ophthalmology consultation between January 2006 and September 2012 in Japan. METHODS: We retrospectively reviewed the ophthalmology consultations of 433 inpatients with positive blood culture results. Clinical features of patients with confirmed chorioretinitis or endophthalmitis were analyzed through descriptive statistical methods and univariate and multivariate models. MAIN OUTCOME MEASURES: Correlation of clinical features with retinal lesions of disseminated bacteremia or fungemia. RESULTS: Among 433 inpatients with positive blood culture results, 116 (26.8%) were unresponsive and 27 (6.2%) had subjective ocular symptoms. Eighty-four (19.4%) had candidemia, including 16 (3.7%) with retinal lesions. Additionally, 34 patients (7.8%) had chorioretinitis or endophthalmitis in 1 eye (17 patients [3.9%]) or both eyes (17 eyes [3.9%]; 51 eyes total). Of these 34 patients, 20 (58.8%) and 17 (50%) had systemic bacterial and fungal infections, respectively (both infections were noted in 3 patients [8.8%]). Staphylococcus aureus was the most common bacteria. Candida albicans was the most common fungus, followed by Candida glabrata. Catheter-related bloodstream infections were the most common source of infection among the 34 patients with chorioretinitis or endophthalmitis, followed by infective endocarditis, urinary tract infection, and soft-tissue and bone disease. Among the 114 bacteremic patients who underwent an ophthalmology consultation because of suspicion of infective endocarditis, only 16 (14%) had infective endocarditis, of whom only 1 (0.88%) had retinal lesions. Nineteen of 34 patients (55.9%) with retinal lesions survived sepsis. Among them, only 1 patient (5.3%) with bacteremia lost significant vision (no light perception), and the remaining 18 patients (94.7%) regained vision. No patient with candidemia had vision loss. Multivariate analysis revealed that candidemia, infective endocarditis, broad-spectrum antibiotic use, and eye symptoms were independent predictors of retinal lesions (all P < 0.05). CONCLUSIONS: An ophthalmology consultation may be useful for patients with candidemia, infective endocarditis, broad-spectrum antibiotic use, or ocular symptoms. However, routine ophthalmologic evaluation may be less efficient for bacteremic patients without definitive infective endocarditis lacking other risk factors.

Ischemic heart disease due to compression of the coronary arteries by malignant lymphoma.

A 76-year-old man presented with a two-month history of angina pectoris. Computed tomography (CT) revealed a serial enlargement of the supraclavicular and mediastinal lymph nodes compressing the heart, pulmonary artery and aorta. CT angiography (CTA) showed stenosis of the coronary arteries as a result of compression by the enlarged lymph nodes. First-pass contrast-enhanced cardiac magnetic resonance imaging (MRI) at rest revealed a perfusion defect, thus indicating myocardial ischemia. Diffuse large B-cell lymphoma was diagnosed and multidrug combination chemotherapy led to prompt improvement of the symptoms. Relief of the stenosis in the coronary arteries and improvements in myocardial perfusion were noted on follow-up CTA and MRI.