Munchausen Syndrome by Tissue Plasminogen Activator: Patients Seeking Thrombolytic Administration.

PURPOSE OF REVIEW: Munchausen syndrome by tissue plasminogen activator (tPA) is a phenomenon we describe as patients exhibiting factitious symptoms to assume the role of the sick patient, desiring and received tPA, with no alternative diagnosis or secondary gain to better account for their presentation. To illustrate this phenomenon and its magnitude, we present a series of cases of Munchausen syndrome by tPA, prevalence in our stroke center, and highlight one illustrative case. RECENT FINDINGS: Of 335 cases with tPA administration over 29 months, 10 were confirmed as Munchausen syndrome by tPA, reflecting a 3.0% prevalence in our stroke center. SUMMARY: Munchausen syndrome by tPA is an underappreciated phenomenon encountered in evaluating patients with acute stroke symptoms. Administering tPA in Munchausen syndrome poses an ethical dilemma because standard of care favors rapid tPA administration, but administration can cause harm, burdens the healthcare system, and does not treat the patient's Munchausen syndrome.

Rostro-Caudal Specificity of Corticospinal Tract Projections in Mice.

Rostro-caudal specificity of corticospinal tract (CST) projections from different areas of the cortex was assessed by retrograde labeling with fluorogold and retrograde transfection following retro-AAV/Cre injection into the spinal cord of tdT reporter mice. Injections at C5 led to retrograde labeling of neurons throughout forelimb area of the sensorimotor cortex and a region in the dorsolateral cortex near the barrel field (S2). Injections at L2 led to retrograde labeling of neurons in the posterior sensorimotor cortex (hindlimb area) but not the dorsolateral cortex. With injections of biotinylated dextran amine (BDA) into the main sensorimotor cortex (forelimb region), labeled axons terminated selectively at cervical levels. With BDA injections into caudal sensorimotor cortex (hindlimb region), labeled axons passed through cervical levels without sending collaterals into the gray matter and then elaborated terminal arbors at thoracic sacral levels. With BDA injections into the dorsolateral cortex near the barrel field, labeled axons terminated at high cervical levels. Axons from medial sensorimotor cortex terminated primarily in intermediate laminae and axons from lateral sensorimotor cortex terminated primarily in laminae III-V of the dorsal horn. One of the descending pathways seen in rats (the ventral CST) was not observed in most mice.

Cyclic hypersomnolence with symptoms of narcolepsy with cataplexy: An unusual presentation of probable immune-mediated encephalitis.

We report a case of probable encephalitis presenting as narcolepsy with cataplexy, but with cyclical exacerbation and cognitive difficulties. Our patient continued to worsen despite treatment for narcolepsy and later was thought to have an immune-mediated encephalopathy. Treatment with intravenous gamma immunoglobulin (IVIG) led to complete recovery. Cyclic symptoms of narcolepsy with cataplexy are thus one presentation of probable immune-mediated encephalitis.

Rodent spinal cord injury models for studies of axon regeneration.

For over a century, axon regeneration has been considered the Holy Grail for spinal cord injury (SCI) repair. Although there are other factors that could contribute to improving function, restoring the long motor and sensory tracts that are interrupted by SCI has the greatest potential for actually reversing paralysis, restoring the brain's control of autonomic functions mediated by sympathetic and parasympathetic circuits of the spinal cord and restoring sensation. Accordingly and in keeping with the overall theme of this special issue, this review focuses narrowly on rodent SCI models for studies of axon regeneration.

Variable laterality of corticospinal tract axons that regenerate after spinal cord injury as a result of PTEN deletion or knock-down.

Corticospinal tract (CST) axons from one hemisphere normally extend and terminate predominantly in the contralateral spinal cord. We previously showed that deleting the gene phosphatase and tensin homolog (PTEN) in the sensorimotor cortex enables CST axons to regenerate after spinal cord injury and that some regenerating axons extend along the "wrong" side. Here, we characterize the degree of specificity of regrowth in terms of laterality. PTEN was selectively deleted via cortical adeno-associated virus (AAV)-Cre injections in neonatal PTEN-floxed mice. As adults, mice received dorsal hemisection injuries at T12 or complete crush injuries at T9. CST axons from one hemisphere were traced by unilateral biotinylated dextran amine (BDA) injections in PTEN-deleted mice with spinal cord injury and in noninjured PTEN-floxed mice that had not received AAV-Cre. In noninjured mice, 97.9 ± 0.7% of BDA-labeled axons in white matter and 88.5 ± 1.0% of BDA-labeled axons in gray matter were contralateral to the cortex of origin. In contrast, laterality of CST axons that extended past a lesion due to PTEN deletion varied across animals. In some cases, regenerated axons extended predominantly on the ipsilateral side; in other cases, axons extended predominantly contralaterally, and in others, axons were similar in numbers on both sides. Similar results were seen in analyses of cases from previous studies using short hairpin (sh)RNA-mediated PTEN knock-down. These results indicate that CST axons that extend past a lesion due to PTEN deletion or knock-down do not maintain the contralateral rule of the noninjured CST, highlighting one aspect of how the resultant circuitry from regenerating axons may differ from that of the uninjured CST. J. Comp. Neurol. 524:2654-2676, 2016. © 2016 Wiley Periodicals, Inc.

Nonspecific labeling limits the utility of Cre-Lox bred CST-YFP mice for studies of corticospinal tract regeneration.

Studies of axon regeneration in the spinal cord often assess regeneration of the corticospinal tract (CST). Emx1-Cre x Thy1-STOP-YFP mice have been reported to have yellow fluorescent protein (YFP) selectively expressed in forebrain neurons leading to genetic labeling of CST axons in the spinal cord, and it was suggested that these CST-YFP mice would be useful for studies of CST regeneration. Because regeneration past a lesion may involve only a few axons, the presence of labeled non-CST axons compromises interpretation. We show here that in CST-YFP mice, some YFP-labeled axons are not from the CST. Specifically, YFP-labeled axons are present in regions beyond those with anterogradely labeled CST axons, most YFP-labeled axons beyond established CST locations do not undergo Wallerian degeneration following a large lesion of the sensorimotor cortex, some rubrospinal and reticulospinal neurons are labeled with YFP, and some YFP-labeled cells in the spinal gray matter have YFP-labeled projections into the spinal cord white matter. We further demonstrate that the density of YFP-labeled axon arbors hinders tracing of single axons to their point of origin in the main descending tracts. In light of recent advances in 3D imaging for visualizing axons in unsectioned blocks of spinal cord, we also assessed CST-YFP mice for 3D imaging and found that YFP fluorescence in CST-YFP mice is faint for clearing-based 3D imaging in comparison with fluorescence in Thy1-YFP-H mice and fluorescence of mini-ruby biotinylated dextran amine (BDA). Overall, the nonspecific and faint YFP labeling in CST-YFP mice limits their utility for assessments of CST axon regeneration.

PTEN deletion enhances the regenerative ability of adult corticospinal neurons.

Despite the essential role of the corticospinal tract (CST) in controlling voluntary movements, successful regeneration of large numbers of injured CST axons beyond a spinal cord lesion has never been achieved. We found that PTEN/mTOR are critical for controlling the regenerative capacity of mouse corticospinal neurons. After development, the regrowth potential of CST axons was lost and this was accompanied by a downregulation of mTOR activity in corticospinal neurons. Axonal injury further diminished neuronal mTOR activity in these neurons. Forced upregulation of mTOR activity in corticospinal neurons by conditional deletion of Pten, a negative regulator of mTOR, enhanced compensatory sprouting of uninjured CST axons and enabled successful regeneration of a cohort of injured CST axons past a spinal cord lesion. Furthermore, these regenerating CST axons possessed the ability to reform synapses in spinal segments distal to the injury. Thus, modulating neuronal intrinsic PTEN/mTOR activity represents a potential therapeutic strategy for promoting axon regeneration and functional repair after adult spinal cord injury.

Unexpected survival of neurons of origin of the pyramidal tract after spinal cord injury.

There is continuing controversy about whether the cells of origin of the corticospinal tract (CST) undergo retrograde cell death after spinal cord injury (SCI). All previous attempts to assess this have used imaging and/or histological techniques to assess upper motoneurons in the cerebral cortex. Here, we address the question in a novel way by assessing Wallerian degeneration and axon numbers in the medullary pyramid of Sprague Dawley rats after both acute SCI, either at cervical level 5 (C5) or thoracic level 9 (T9), and chronic SCI at T9. Our findings demonstrate that only a fraction of a percentage of the total axons in the medullary pyramid exhibit any sign of degeneration at any time after SCI--no more so than in uninjured control rats. Moreover, design-based counts of myelinated axons revealed no decrease in axon number in the medullary pyramid after SCI, regardless of injury level, severity, or time after injury. Spinal cord-injured rats had fewer myelinated axons in the medullary pyramid at 1 year after injury than aged matched controls, suggesting that injury may affect ongoing myelination of axons during aging. We conclude that SCI does not cause death of the CST cell bodies in the cortex; therefore, therapeutic strategies aimed at promoting axon regeneration of the CST in the spinal cord do not require a separate intervention to prevent retrograde degeneration of upper motoneurons in the cortex.

Changes in adjacent-level disc pressure and facet joint force after cervical arthroplasty compared with cervical discectomy and fusion.

OBJECT: The authors of previous in vitro investigations have reported an increase in adjacent-level intradiscal pressures (IDPs) and facet joint stresses following cervical spine fusion. This study was performed to compare adjacent-level IDPs and facet force following arthroplasty with the fusion model. METHODS: Eighteen human cadaveric cervical spines were tested in the intact state for different modes of motion (extension, flexion, bending, and rotation) up to 2 Nm. The specimens were then divided into three groups: those involving the ProDisc-C cervical artificial disc, Prestige cervical artificial disc, and cervical fusion. They were load tested after application of instrumentation or surgery at the C6-7 level. During the test, IDPs and facet forces were measured at adjacent levels. RESULTS: In arthroplasty-treated specimens, the IDP showed little difference from that of the intact spine at both proximal and distal levels. In fusion-treated specimens, the IDP increased at the posterior anulus fibrosus on extension and at the anterior anulus fibrosus on flexion at the proximal level. At the distal level, the IDP change was not significant. The facet force changes were minimal in flexion, bending, and rotation modes in both arthroplasty- and fusion-treated spines. Significant changes were noted in the extension mode only. In extension, arthroplasty models exhibited significant increases of facet force at the treated level. In the fusion model the facet forces decreased at the treated segment and increased at the adjacent segment. CONCLUSIONS: The two artificial discs of the semiconstrained systems maintain adjacent-level IDPs near the preoperative values in all modes of motion, but with respect to facet force pressure tended to increase after arthroplasty.

Range of motion change after cervical arthroplasty with ProDisc-C and prestige artificial discs compared with anterior cervical discectomy and fusion.

OBJECT: Range of motion (ROM) changes were evaluated at the surgically treated and adjacent segments in cadaveric specimens treated with two different cervical artificial discs compared with those measured in intact spine and fusion models. METHODS: Eighteen cadaveric human cervical spines were tested in the intact state for the different modes of motion (extension, flexion, lateral bending, and axial rotation) up to 2 Nm. Three groups of specimens (fitted with either the ProDisc-C or Prestige II cervical artificial disc or submitted to anterior cervical discectomy and fusion [ACDF]) were tested after implantation at C6-7 level. The ROM values were measured at treated and adjacent segments, and these values were then compared with those measured in the intact spine. RESULTS: At the surgically treated segment, the ROM increased after arthroplasty compared with the intact spine in extension (54% in the ProDisc-C group, 47% in the Prestige group) and in flexion (27% in the ProDisc-C group, 10% in the Prestige group). In bending and rotation, the postarthroplasty ROMs were greater than those of the intact spine (10% in the ProDisc-C group and 55% in the Prestige group in bending, 17% in the ProDisc-C group and 50% in the Prestige group in rotation). At the adjacent levels the ROMs decreased in all specimens treated with either artificial disc in all modes of motion (< 10%) except for extension at the inferior the level (29% decrease for ProDisc-C implant, 12% decrease for Prestige disc). The ROM for all motion modes in the ACDF-treated spine decreased at the treated level (range 18-44%) but increased at the adjacent levels (range 3-20%). CONCLUSIONS: Both ProDisc-C and Prestige artificial discs were associated with increased ROM at the surgically treated segment compared with the intact spine with or without significance for all modes of testing. In addition, adjacent-level ROM decreased in all modes of motion except extension in specimens fitted with both artificial discs.

Comparison of the biomechanical stability of dense cancellous allograft with tricortical iliac autograft and fibular allograft for cervical interbody fusion.

Several choices are available for cervical interbody fusion after anterior cervical discectomy. A recent option is dense cancellous allograft (CS) which is characterized by an open-matrix structure that may promote vascularization and cellular penetration during early osseous integration. However, the biomechanical stability of CS should be comparable to that of the tricortical iliac autograft (AG) and fibular allograft (FA) to be an acceptable alternative to these materials. The purpose of this study was to compare the initial biomechanical stability of CS to that of AG and FA in a one-level anterior cervical discectomy and interbody fusion (ACDF) model. Twelve human cervical spines (C3-T1) were loaded in six modes of motion and evaluated under three conditions: (1) intact, (2) after ACDF using CS, AG, and FA in alternating sequences, and (3) after ACDF with anterior plating. Three reflective markers were placed on the adjacent vertebral bodies. Intervertebral motion was measured with a video-based motion-capture system (MacReflex, Qualisys, Sweden). Torques were applied to a maximum of 2.0 N m. The range-of-motion and neutral-zone values measured in each loading mode were compared. No graft material displayed significant differences in biomechanical stability in any of the tested loading modes, suggesting that the initial stability of CS is comparable to that of AG and FA. Anterior cervical plating significantly increased biomechanical stability in all modes.