Numerous spindle-shaped lymphoma cells in lymphomatosis cerebri: An autopsy case report.

Lymphomatosis cerebri (LC) is a rare variant of primary central nervous system lymphoma (PCNSL). It is characterized by diffuse infiltration of atypical lymphoid cells with no mass formation and little or no contrast enhancement on magnetic resonance imaging (MRI). Interestingly, some lymphoma cells form characteristic spindle shapes; these cells are found in some variants of malignant lymphoma, such as primary cutaneous follicle center lymphoma, but they have not been reported in PCNSL or LC. Here, we provide an autopsy case report of LC in a 69-year-old immunocompetent man who developed rapidly progressive cognitive decline and died on day 68 after the episode despite treatment with intravenous methylprednisolone administration. MRI revealed high signal intensities on T2-weighted images of the cerebral hemispheres, cerebellum, brainstem, and spinal cord without gadolinium enhancement on T1-weighted images. On autopsy, diffuse infiltrative atypical cells were seen; these cells were positive for CD20 and CD79a and negative for GFAP, CD3, and CD5 on immunohistochemistry, resulting in a diagnosis of diffuse large B-cell lymphoma, specifically LC. We found characteristic spindle-shaped cells, especially in the cerebral cortex. This is the first report showing that lymphoma cells in PCNSL can take on a spindle-shaped form. It is difficult to recognize these spindle-shaped cells as lymphoma cells on hematoxylin and eosin staining and diagnose them correctly with small biopsy specimens without immunohistochemistry. This case suggests that we should add atypical, spindle-shaped cells to the differential diagnosis of PCNSL.

Combined laser in-situ keratomileusis and accelerated corneal cross-linking: an update.

PURPOSE OF REVIEW: The purpose is to review the literature of combined laser in-situ keratomileusis (LASIK) and accelerated corneal collagen cross-linking (CXL) in context of its indications-contraindications, kerato-refractive, visual and safety outcomes, particularly with reference to preventing the development of post-LASIK ectasia. RECENT FINDINGS: LASIK + accelerated CXL has been developed with the rationale that the addition of CXL after LASIK may strengthen the LASIK compromised corneal biomechanics and minimize the complications such as post-LASIK ectasia. Different clinical studies have documented the safety and efficacy of LASIK + accelerated CXL for the correction of myopia or hyperopia and in the patients with low predicted residual bed thickness. SUMMARY: Available literature shows that refractive and keratometric outcomes of LASIK + accelerated CXL are comparable or better than LASIK alone. Less regression has been observed after LASIK + accelerated CXL compared with LASIK alone and no case of post-LASIK ectasia development has been reported among 673 eyes with the follow-up ranging from 3 months to 4.5 years. Future studies with large numbers of patients and longer postoperative follow-ups are needed to establish the efficacy of LASIK + accelerated CXL in preventing the development of post-LASIK ectasia.

Evaluating the short-term results of KAMRA inlay implantation using real-time optical coherence tomography-guided femtosecond laser technology.

PURPOSE: To evaluate the outcomes from using real-time optical coherence tomography (OCT)-guided femtosecond laser technology for pocket creation for KAMRA inlay (Acufocus, Inc., Irvine, CA) implantation surgery. METHODS: One hundred fifty-one eyes underwent KAMRA inlay implantation using the real-time OCT-guided femtosecond laser for pocket creation. All patients had a history of prior LASIK. Uncorrected distance visual acuity, corrected distance visual acuity, uncorrected near visual acuity, corrected near visual acuity, and manifest refraction spherical equivalent were evaluated preoperatively and postoperatively. The follow-up period was 3 months. RESULTS: Mean manifest refraction spherical equivalent, uncorrected distance visual acuity, and uncorrected near visual acuity changed from -0.18 ± 0.33 to -0.95 ± 0.64, 20/16 to 20/20, and J8 to J2, respectively. Corrected distance visual acuity and corrected near visual acuity remained stable before and after KAMRA inlay implantation, 20/12 and J1, respectively. CONCLUSIONS: Using real-time OCT-guided femtosecond laser technology increases the safety and accuracy of corneal KAMRA inlay implantation surgery with a history of prior LASIK with excellent visual and refractive outcomes.

Retrospective evaluation of the influence of pupil size on visual acuity after KAMRA inlay implantation.

PURPOSE: To investigate the influence of pupil size on visual acuity after KAMRA inlay (AcuFocus, Inc., Irvine, CA) implantation. METHODS: Five hundred eighty-four presbyopic eyes of 584 patients who underwent LASIK were evaluated. Uncorrected near visual acuity (UNVA), uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and corrected near visual acuity (CNVA) were measured. Two groups were classified: small pupil (pupil diameter < 6 mm) and large pupil (pupil diameter ≥ 6 mm) for both mesopic (pupil diameter < 4 mm) and photopic (pupil diameter ≥ 4 mm) pupil size parameters. The follow-up period was 6 months. RESULTS: There were no significant differences in UNVA (P = .98) and CNVA (P = .16) between the mesopic pupil size groups; however, there were significant differences in UDVA (P = .023) and CDVA (P = .039). There was a weak correlation between pupil size and UDVA of the large mesopic pupil size group (rs = 0.129, P = .04). There were no significant differences in UNVA (P = .78), CNVA (P = .92), UDVA (P = .19), and CDVA (P = .60) for the photopic pupil size groups. CONCLUSIONS: Pupil size does not have an influence on the resultant visual acuity after KAMRA inlay implantation. No correlation was found between preoperative and postoperative pupil size and visual acuity for the mesopic pupil groups.

Outcomes of small aperture corneal inlay implantation in patients with pseudophakia.

PURPOSE: To evaluate the improvement in near visual acuity after KAMRA corneal inlay (AcuFocus, Inc., Irvine, CA) implantation in patients with pseudophakia. METHODS: A retrospective study analysis of patients with pseudophakia undergoing monocular corneal inlay implantation in the non-dominant eye was performed. The inlay was implanted monocularly in the non-dominant eye of patients. Manifest refractive spherical equivalent, uncorrected distance visual acuity, corrected distance visual acuity, uncorrected near visual acuity, and corrected near visual acuity were evaluated. The follow-up period was 3 months. RESULTS: Thirteen eyes from 13 patients were evaluated. Four patients underwent LASIK for improved distance acuity at the time of inlay implantation. Mean uncorrected near visual acuity improved five lines (from J10 to J4) postoperatively. Mean uncorrected distance visual acuity, corrected distance visual acuity, and corrected near visual acuity remained stable and were 20/20, 20/16, and J1, respectively, before and after KAMRA implantation. Three eyes lost two lines and 1 eye lost one line of uncorrected distance visual acuity. Two eyes lost two lines and 1 eye lost 1 line of corrected distance visual acuity. Mean manifest refractive spherical equivalent changed before and after KAMRA implantation from -0.01 ± 1.07 diopters (D) (range: 2.25 to -1.88 D) to -1.12 ± 0.87 D (range: 0.25 to -2.75 D), respectively. CONCLUSIONS: Implantation of a small aperture corneal inlay improved uncorrected near visual acuity while maintaining uncorrected and corrected distance visual acuity in monofocal patients with pseudophakia.

Clinicopathological features of neuropathy associated with lymphoma.

Lymphoma causes various neurological manifestations that might affect any part of the nervous system and occur at any stage of the disease. The peripheral nervous system is one of the major constituents of the neurological involvement of lymphoma. In this study we characterized the clinical, electrophysiological and histopathological features of 32 patients with neuropathy associated with non-Hodgkin's lymphoma that were unrelated to complications resulting from treatment for lymphoma. Nine patients had pathologically-proven neurolymphomatosis with direct invasion of lymphoma cells into the peripheral nervous system. These patients showed lymphomatous cell invasion that was more prominent in the proximal portions of the nerve trunk and that induced demyelination without macrophage invasion and subsequent axonal degeneration in the portion distal from the demyelination site. Six other patients were also considered to have neurolymphomatosis because these patients showed positive signals along the peripheral nerve on fluorodeoxyglucose positron emission tomography imaging. Spontaneous pain can significantly disrupt daily activities, as frequently reported in patients diagnosed with neurolymphomatosis. In contrast, five patients were considered to have paraneoplastic neuropathy because primary peripheral nerve lesions were observed without the invasion of lymphomatous cells, with three patients showing features compatible with chronic inflammatory demyelinating polyneuropathy, one patient showing sensory ganglionopathy, and one patient showing vasculitic neuropathy. Of the other 12 patients, 10 presented with multiple mononeuropathies. These patients showed clinical and electrophysiological features similar to those of neurolymphomatosis rather than paraneoplastic neuropathy. Electrophysiological findings suggestive of demyelination were frequently observed, even in patients with neurolymphomatosis. Eleven of the 32 patients, including five patients with neurolymphomatosis, fulfilled the European Federation of Neurological Societies/Peripheral Nerve Society electrodiagnostic criteria of definite chronic inflammatory demyelinating polyneuropathy. Some of these patients, even those with neurolymphomatosis, responded initially to immunomodulatory treatments, including the administration of intravenous immunoglobulin and steroids. Patients with lymphoma exhibit various neuropathic patterns, but neurolymphomatosis is the major cause of neuropathy. Misdiagnoses of neurolymphomatosis as chronic inflammatory demyelinating polyneuropathy are frequent due to a presence of a demyelinating pattern and the initial response to immunomodulatory treatments. The possibility of the concomitance of lymphoma should be considered in various types of neuropathy, even if the diagnostic criteria of chronic inflammatory demyelinating polyneuropathy are met, particularly in patients complaining of pain.

Demyelinating Neuropathy with Markedly Elevated Serum IgG4 Levels and Anti-Contactin 1 IgG4 Antibody.

We herein report a 77-year-old man with a 4-month history of progressive gait and sensory disturbances of the extremities. A nerve conduction study indicated demyelinating polyneuropathy. Serum IgG4 levels and anti-contactin 1 IgG4 antibodies were markedly increased. The sural nerve biopsy specimen showed IgG4-positive plasma cell infiltration in the epineurium. Treatment with steroids resulted in an amelioration of functional status, improvement of nerve conduction parameters, decreased serum IgG4 levels, and negative conversion of anti-contactin 1 antibody. Further studies are needed to clarify the significance of IgG4-positive plasma cell infiltration in anti-contactin 1 antibody-positive neuropathies.

Sustained decrease and remarkable increase in red blood cell velocity in intraparenchymal capillaries associated with potassium-induced cortical spreading depression.

OBJECTIVES: To examine changes in red blood cell (RBC) velocity in intraparenchymal capillaries of rat cerebral cortex in response to KCl-induced cortical spreading depression (CSD). METHODS: In isoflurane-anesthetized rats, the velocity of fluorescently labeled RBCs flowing in capillaries in layer I was measured with a high-speed camera laser-scanning confocal fluorescence microscope, with simultaneous monitoring of DC potential, the electroencephalogram (EEG), partial pressure of oxygen (PO(2) ), and cerebral blood flow (CBF). RESULTS: After KCl application, a transient deflection of DC potential (i.e., CSD) repeatedly appeared concomitantly with depression of EEG, and was propagated in the distal direction. PO(2) transiently decreased and CBF was slowly elevated. The frequency distribution of RBC velocity was shifted downward during CSD and was still low after the passage of CSD. When we observed RBC velocity in 38 individual capillaries, 10 capillaries exhibited slowed-down RBC during CSD and RBC velocity remained low in 2 even after the passage of CSD. On the other hand, RBCs with moderately (<3 mm/sec) or remarkably (>3 mm/sec) increased velocities were seen in 10 and 5 capillaries, respectively. CONCLUSION: CSD-induced excitation of neurons may sustainably decrease or greatly increase RBC velocity in capillaries.

Natural history of transthyretin Val30Met familial amyloid polyneuropathy: analysis of late-onset cases from non-endemic areas.

OBJECTIVE: The objective of this study was to elucidate the natural history of late-onset transthyretin Val30Met-associated familial amyloid polyneuropathy (FAP ATTR Val30Met) in non-endemic areas. METHODS: The authors retrospectively assessed the development of major clinical landmarks and abnormalities of nerve conduction and cardiac examination indices in 50 patients with an age of onset older than 50 years and no relationship to endemic foci. RESULTS: Once the neuropathic process was initiated, sensory and motor symptoms of both the upper and lower extremities appeared within a period of one and a half years. Digestive and orthostatic symptoms also tended to occur in the early phase of the disease, whereas urinary symptoms appeared in the middle of the disease progress. Along with pain in the extremities, these symptoms progressed over time and significantly disturbed the quality of life during the late phase of the disease, resulting in the need for wheelchair use. Although cardiomyopathy became clinically apparent only in the late phase of the disease, it was found to be the major cause of death. The mean duration of the disease onset to death was 7.3 years. Although values at the time of diagnosis were extremely variable, serial measurements of electrophysiological indices, the cardiothoracic ratio and interventricular septum thickness indicated a steady exacerbation in these outcomes among patients within a span of a couple of years. CONCLUSIONS: The ages of onset of each clinical landmark were extremely variable between patients. However, once an initial symptom appeared, the chronological sequence of other clinical landmarks tended to be uniform, occurring within a relatively short time span.

Impact of aging on the progression of neuropathy after liver transplantation in transthyretin Val30Met amyloidosis.

INTRODUCTION: Information related to the long-term follow-up of neuropathy in patients with familial amyloid polyneuropathy after liver transplantation is still scarce. METHODS: We describe the neuropathic features of 3 patients with the transthyretin Val30Met mutation. Each patient underwent liver transplantation at an early stage of neuropathy, as indicated by the absence of motor dysfunction and relative preservation of myelinated fibers in sural nerve biopsy specimens. RESULTS: Although the patient with late-onset disease (at age 60 years) presented with the least amount of amyloid deposition, he had neuropathic progression after liver transplantation. An older early-onset (at age 40 years) patient reported a slight exacerbation of both somatic and autonomic neuropathic symptoms 10 years after transplantation. However, the younger early-onset (at age 28 years) patient did not exhibit characteristics suggestive of neuropathy 7 years after transplantation. CONCLUSION: Aging may determine the progression of neuropathy after liver transplantation.

Evaluation of LASIK treatment with the Femto LDV in patients with corneal opacity.

PURPOSE: To evaluate the relative effectiveness and safety of LASIK using the Femto LDV (Ziemer Ophthalmic Systems AG) and IntraLase FS 60 (Abbott Medical Optics Inc) femtosecond lasers in patients with corneal opacity. METHODS: Patients with corneal opacity were retrospectively selected between March and July 2009. For this study, 205 eyes with 90-µm corneal flaps created using the Femto LDV (LDV group) and 200 eyes with corneal flaps created using the IntraLase FS 60 (Intra-Lase group) were selected. The flap thickness of the IntraLase group was determined by observation with slit-lamp microscopy. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and manifest refraction spherical equivalent (MRSE) were measured pre- and postoperatively and were statistically evaluated using the Student t test and Mann-Whitney U-test. RESULTS: Regardless of the levels of opacity, eyes in the LDV group experienced uneventful procedures with no complications. Eyes in the IntraLase group had corneal flaps of 100- to 130-µm thickness and uneventful procedures; however, gas breakthrough was observed in 27 eyes. Of all eyes, 117 eyes from the LDV group and 109 eyes from the IntraLase group were available for 3-month follow-up. Mean 3-month postoperative UDVA, CDVA, and MRSE for the LDV group were 20/12.5, 20/12.5, and 0.17±0.32 diopters (D), respectively, and for the IntraLase group were 20/12.5, 20/12.5, and 0.11±0.34 D, respectively. No statistically significant differenes were noted in UDVA, CDVA, or MRSE between groups (P>.05 for all). CONCLUSIONS: Laser in situ keratomileusis with the Femto LDV created thin flaps regardless of level of opacity and induced no complications as compared to the IntraLase FS 60, where gas breakthrough was significantly more common.

Management and outcomes of suction loss during LASIK flap creation with a femtosecond laser.

PURPOSE: To evaluate risk factors, management, and outcomes in patients who experienced suction loss during LASIK flap creation with a femtosecond laser (Intra-Lase FS 60, Abbott Medical Optics Inc). METHODS: Pre- and postoperative visual outcomes and refractions for 71 eyes of 70 patients after suction loss during flap creation with the IntraLase FS60 femtosecond laser were analyzed and studied. RESULTS: In patients requiring a second or third lamellar flap cut immediately after suction loss, 97.2% of eyes achieved uncorrected distance visual acuity of 0.00 logMAR (20/20) or better and 100% of eyes achieved corrected distance visual acuity of 0.00 logMAR (20/20) or better at most recent follow-up. CONCLUSIONS: Our study suggests that excellent visual outcomes can be achieved if an immediate lamellar recut is performed after suction loss with a femtosecond laser.

Oscillating neuro-capillary coupling during cortical spreading depression as observed by tracking of FITC-labeled RBCs in single capillaries.

Coupling between capillary red blood cell (RBC) movements and neuronal dysfunction during cortical spreading depression (CSD) was examined in rats by employing a high-speed camera laser-scanning confocal fluorescence microscope system in conjunction with our Matlab domain software (KEIO-IS2). Following microinjection of K(+) onto the surface of the brain, changes in electroencephalogram (EEG), DC potential and tissue optical density were all compatible with the occurrence of a transient spreading neuronal depression. RBC flow in single capillaries was not stationary. Unpredictable redistribution of RBCs at branches of capillaries was commonly observed, even though no change in diameter was apparent at the reported site of the capillary sphincter and no change of arteriolar-venule pressure difference was detected. There appeared to be a slow morphological change of astroglial endfeet. When local neurons were stunned transiently by K(+) injection, the velocity and oscillation frequency of RBCs flowing in nearby capillaries started to decrease. The flow in such capillaries was rectified, losing oscillatory components. Sluggish floating movements of RBCs in pertinent capillaries were visualized, with occasional full stops. When CSD subsided, RBC movements recovered to the original state. We postulate that neuronal depolarization blocks oscillatory signaling to local capillaries via low-shear plasma viscosity increases in the capillary channels, and a complex interaction between the RBC surface and the buffy coat on the capillary wall surface increases the capillary flow resistance. Then, when CSD subsides and oscillatory neuronal function is recovered, the normal physiological conditions are restored.

Developmental and circulatory profile of the diploic veins.

To examine the development of the diploic veins in the calvarium, FITC-dextran was injected into the tail vein. The total area of the diploic veins showed a continuous, age-dependent development. We also measured the red blood cell (RBC) velocities in the diploic veins using an in vivo imaging technique and revealed RBCs with a significantly high velocity and unidirectional characteristics at the entrance route. The route passed from the basal periosteum of the cranial bone via the dura mater and into the diploic veins. Our findings indicate the existence of communications between intra- and extra-cranial circulation.

Systemic but asymptomatic transthyretin amyloidosis 8 years after domino liver transplantation.

As familial amyloid polyneuropathy (FAP) is an adult-onset disease, a long period is expected between domino liver transplantation (DLT) and the occurrence of amyloidosis in recipients of a FAP liver. However, as time passes, and increased numbers of patients have undergone DLT, patients with symptoms suggesting amyloidosis have been reported. The authors describe, for the first time, pathological findings in an autopsy case of a recipient of a FAP liver. A male patient with primary sclerosing cholangitis received a liver graft from a FAP patient with the transthyretin (TTR) Tyr114Cys mutation when he was 30 years old. Although a recurrence of primary sclerosing cholangitis was detected at age 34, he had no symptoms indicating amyloidosis. He died from Burkitt's lymphoma at 38 years of age. TTR immunoreactive amyloid was found in various organs including the heart, lung, gastrointestinal tract, pancreas, spleen, reproductive system and skeletal muscles. In the nervous system, TTR immunoreactive amyloid deposition was obvious in the sympathetic ganglia and the median nerve within the carpal tunnel, while loss of neurons or nerve fibres was not apparent. This case allows for the characterisation of amyloid deposition during the asymptomatic stage of FAP. Widespread amyloid deposition may occur before tissue damage in this disease.

Morphological and mechanical properties of muscle and tendon in highly trained sprinters.

The purpose of this study was to investigate muscle and tendon properties in highly trained sprinters and their relations to running performance. Fifteen sprinters and 15 untrained subjects participated in this study. Muscle thickness and tendon stiffness of knee extensors and plantar flexors were measured. Sprinter muscle thickness was significantly greater than that of the untrained subjects for plantar flexors, but not for knee extensors (except for the medial side). Sprinter tendon stiffness was significantly lower than that of the untrained subjects for knee extensors, but not for plantar flexors. The best official record of a 100-m race was significantly correlated to the muscle thickness of the medial side for knee extensors. In conclusion, the tendon structures of highly trained sprinters are more compliant than those of untrained subjects for knee extensors, but not for plantar flexors. Furthermore, a thicker medial side of knee extensors was associated with greater sprinting performance.

Dually supplied T-junctions in arteriolo-arteriolar anastomosis in mice: key to local hemodynamic homeostasis in normal and ischemic states?

BACKGROUND AND PURPOSE: The functional role of arteriolo-arteriolar anastomosis (AAA) between the middle cerebral artery (MCA) and anterior cerebral artery in local hemodynamics is unknown, and was investigated here. METHODS: Blood flow in AAAs was examined using fluorescein isothiocyanate-labeled red blood cells (RBCs) as a flow indicator in 16 anesthetized C57BL/6J mice before and after MCA occlusion up to 7 experimental days. RESULTS: We observed paradoxical flow in AAAs; labeled RBCs entered from both the MCA and anterior cerebral artery sides and the opposing flows met at a branching T-junction, where the flows combined and passed into a penetrating arteriole. The dually fed T-junction was not fixed in position, but functionally jumped to adjacent T-junctions in response to changing hemodynamic conditions. On MCA occlusion, RBC flow from the MCA side immediately stopped. After a period of "hesitation," blood started to move retrogradely in one of the MCA branches toward the MCA stem. The retrograde blood flow was statistically significantly (P<0.05), serving to feed blood to other MCA branches after a lag period. In capillaries, MCA occlusion induced immediate RBC disappearance in the ischemic core and to a lesser extent in the marginal zone near AAAs. At day 3 after ischemia, we recognized the beginning of remodeling with angiogenesis centering on AAAs. CONCLUSIONS: AAAs appear to play a key role in local hemodynamic homeostasis, both in the normal state and in the development of collateral channels and revascularization during ischemia.

Inflammation-induced lymphangiogenesis in the cornea arises from CD11b-positive macrophages.

In the inflamed cornea, there is a parallel outgrowth of blood and lymphatic vessels into the normally avascular cornea. We tested whether adaptive and/or innate immune cells were actively involved in the genesis of new lymphatic vessels. Our results indicate that innate immune cells (CD11b+ macrophages, but not CD11c+ dendritic cells) physically contributed to lymphangiogenesis under pathological conditions and that bone marrow-derived CD11b+ macrophages expressed lymphatic endothelial markers such as LYVE-1 and Prox-1 under inflamed conditions in the corneal stromata of mice. Furthermore, blood vascular endothelial cells that expressed the Tie2 promoter did not contribute to newly formed lymphatic vessels under inflamed conditions. Our in vitro experiments demonstrated that CD11b+ macrophages alone were capable of forming tube-like structures that expressed markers of lymphatic endothelium such as LYVE-1 and podoplanin. The novel finding that CD11b+ macrophages are critical for the development of inflammation-dependent lymphangiogenesis in the eye suggests a new mechanism of lymphangiogenesis.