Primary central nervous system post-transplant lymphoproliferative disease (CNS PTLD) is a serious complication after solid organ transplantation that has not received much attention so far. However, it could become a more frequent problem with the introduction of new biological agents.
We present a novel approach to quantify skin innervation by measuring the PGP 9.5 immunoreactive (PGP-ir) fluorescence corresponding to axons within the epidermis and dermis. The skin biopsies from 35 controls and 45 small fiber neuropathy (SFN) patients were included. In 50-?m free-floating sections, we determined the intraepidermal nerve fiber density (IENFD) by direct fluorescence visualization and captured 2-?m thick individual optical sections using the same confocal microscope and magnification. We measured the fluorescence of the PGP-ir axons in both, epidermal and dermal area by using the ImageJ software. There was good interobserver and intraobserver reliability of PGP-ir measures, similar than for IENFD. The PGP-ir axons were found decreased in patients with SFN (1.1‰ and 9.0‰ respectively for epidermal and dermal area in contrast to 2.2‰ and 16.0‰, respectively to controls). The area under the ROC curve was 0.90 for the IENFD, 0.84 for epidermal PGP-ir axons and 0.70 for dermal PGP-ir axons. There was a positive correlation between the IENFD and the PGP-ir axons at epidermis (Spearman Rho=0.66, p<0.001) as well as for the dermal nerve length and the PGP-ir axons at dermis (Spearman Rho=0.45, p<0.05). This method is also particularly adequate for the quantitation of dermal nerve fibers. We conclude that quantifying the fluorescent PGP-ir axons could help to assess skin innervation (dermal and epidermal nerve fibers) in patients with SFN.
Paraneoplastic cerebellar degeneration (PCD) is characterized by a subacute, severe pancerebellar syndrome, which is related to an underlying tumor. The presence of CSF or serum onconeural antibodies confirms the diagnosis and indicates the underlying tumor type. However, the association between PCD and extragonadal germ cell tumors with the absence of an onconeural antibody has rarely been described. We present a 55-year-old man who developed a pancerebellar syndrome, which made him unable to walk alone after 10months. Routine blood analysis, brain MRI and CSF examination were normal. Despite onconeural antibodies were negative, a whole body PET-CT scan showed a hypermetabolic nodule in the thymus, which was removed, and a hypometabolic presacral mass. The pathologic study revealed a germinoma surrounded by a pronounced inflammatory infiltrate. Shortly after, the patient clearly improved his symptoms, before receiving chemotherapy and prednisone. The cerebellar ataxia worsened when steroids were reduced below 30mg/day. Testicular sonography showed a suspicious lesion in one testicle, but no malignancy was found after orchiectomy. The presacral mass was removed after chemotherapy disclosing a mature teratoma. Our patient emphasizes that despite the absence of onconeural antibodies, studies to rule out an underlying tumor are mandatory in patients with subacute cerebellar ataxia.
Evaluation of nerve fibers in the skin provides a useful tool for the diagnosis of small fiber neuropathies (SFNs). Our aim was to determine whether mitochondria are involved in SFN, indicating early axonal damage. We quantified mitochondrial respiratory chain complex IV (OXPHOS) and axonal (PGP 9.5) fluorescence on skin sections from 32 SFN patients and 14 healthy controls. Also, a group of six patients were recruited before and after 30-day treatment with the mitotoxic antibiotic linezolid. We measured the co-localization of OXPHOS within the intraepidermal and subpapillary dermal axons (PGP-immunoreactive [PGP-ir]). SFN patients with relatively preserved intraepidermal nerve fibers (SFN borderline) showed statistically significant reduction of OXPHOS (50.5 ± 33.9 µm(2) vs. 107.6 ± 81 µm(2) in controls, p < 0.02). A positive correlation was found between both PGP-ir and OXPHOS in controls (Pearsons coefficient r = 0.59, p < 0.001), whereas such correlation was absent in SFN. With respect to baseline measurements, linezolid therapy increased both PGP-ir and OXPHOS, which could be considered an initial compensatory toxic-induced response. This study set out to identify a possible marker of axonal pre-degenerative state in SFN borderline patients.
Correct diagnosis of rapid eye movement sleep behavior disorder (RBD) is important because it can be the first manifestation of a neurodegenerative disease, it may lead to serious injury, and it is a well-treatable disorder. We evaluated the electromyographic (EMG) activity in the Sleep Innsbruck Barcelona (SINBAR) montage (mentalis, flexor digitorum superficialis, extensor digitorum brevis) and other muscles to obtain normative values for the correct diagnosis of RBD for clinical practice.
Contactin-2 was recently identified as an autoantigen targeted by T-cells and autoantibodies in multiple sclerosis (MS). Here we analyzed the frequency of antibodies to contactin-2 (contactin-2-ab) by a cell-based assay in the serum from 105 MS patients and at least 5 years of follow-up (19 clinically isolated syndromes, 51 relapsing-remitting, 20 secondary-progressive, and 15 primary-progressive). Contactin-2-ab were detected in 4 (7.8%) relapsing-remitting patients. Clinical and magnetic resonance imaging characteristics were not significantly different from the rest of relapsing-remitting patients. In conclusion, contactin-2-ab are identified in a minority of MS patients but their presence is not associated with a particular clinical-radiological profile.
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