Madhavan, Ajay A.

Tolosa–Hunt syndrome is characterized by unilateral retro-orbital headaches and cranial nerve palsies, usually involving cranial nerves III–VI. It is rare for other cranial nerves to be involved, although this has previously been reported. We report a 19-year-old woman presenting with typical features of Tolosa–Hunt syndrome but ultimately developing bilateral facial nerve palsies and enhancement of both facial nerves on magnetic resonance imaging. The patient presented with unilateral retro-orbital headaches and palsies of cranial nerves III–VI. She was diagnosed with Tolosa–Hunt syndrome but was non-compliant with her corticosteroid treatment due to side effects. She returned with progressive left followed by right facial nerve palsy. Her corresponding follow-up magnetic resonance imaging scans showed sequential enhancement of the left and right facial nerves. She ultimately had clinical improvement with IV methylprednisolone. To our knowledge, Tolosa–Hunt syndrome associated with bilateral facial nerve palsy and corroborative facial nerve enhancement on magnetic resonance imaging has not previously been described. Moreover, our patient’s clinical course is instructive, as it demonstrates that this atypical presentation of Tolosa–Hunt syndrome can indeed respond to corticosteroid treatment and should not be mistaken for other entities such as Bell’s palsy.

A 69-year-old female presented with subacute onset ascending weakness and paraesthesias. She was initially diagnosed with Guillain–Barré syndrome (GBS) based on her clinical presentation and cerebrospinal fluid (CSF) analysis showing albuminocytological dissociation. However, she was later found to have anti-neuronal nuclear antibody 1 (ANNA-1/anti-Hu)-positive CSF and was subsequently diagnosed with small-cell lung cancer. Her neurological symptoms were ultimately attributed to ANNA-1/anti-Hu-associated paraneoplastic polyneuropathy. During the course of her evaluation, she had magnetic resonance imaging findings of dorsal predominant cauda equina nerve root enhancement, which has not been previously described. The only previously reported case of cauda equina enhancement due to ANNA-1-associated polyneuropathy described ventral predominant findings. The distinction between ventral and dorsal enhancement is important, since it suggests that different patterns of nerve root involvement may be associated with this paraneoplastic syndrome. Therefore, ANNA-1-associated paraneoplastic inflammatory polyneuropathy can be considered in the differential diagnosis of cauda equina nerve root enhancement with ventral and/or dorsal predominance. This can potentially be helpful in differentiating ANNA-1 polyneuropathy from GBS, which classically has ventral predominant enhancement.

Stem cell treatment outside of studied and approved medical indications can have unforeseen adverse consequences. Here, we present a 74-year-old male that underwent such therapy. The patient presented to our institution with progressive lower extremity weakness and urinary incontinence. He had previously undergone intrathecal stem cell therapy in Moscow, Russia for weakness and fatigue. Magnetic resonance imaging of his thoracic and lumbar spine showed marked enlargement of the cauda equina nerve roots and abnormal mass-like soft tissue involving the thoracolumbar thecal sac. Surgical biopsy of the intrathecal soft tissue showed polyclonal lymphocytic and glial cell proliferation. The patient’s symptoms did not improve with medical treatment or radiation, and he is currently under observation after multidisciplinary evaluation. Our patient’s experience illustrates one of the potential risks of “stem cell tourism” and exemplifies the imaging and histopathologic features of this rare entity. We also compare our patient’s treatment with other similar examples of stem cell treatments in our institution and others. These have had a wide spectrum of results. In some instances, intrathecal stem cells have caused abnormal imaging findings without any associated patient symptoms. In extreme examples, however, stem cell treatments have resulted in central nervous system neoplasms. Our patient’s lesion is quite unique, with only one similar lesion having been previously published.

Background: Different clinical syndromes can arise from Alzheimer’s disease (AD) neuropathology, including dementia of the Alzheimer’s type (DAT), logopenic primary progressive aphasia (lvPPA), and posterior cortical atrophy (PCA). Objective: To assess similarities and differences in patterns of white matter tract degeneration across these syndromic variants of AD. Methods: Sixty-four subjects (22 DAT, 24 lvPPA, and 18 PCA) that had diffusion tensor imaging and showed amyloid-β deposition on PET were assessed in this case-control study. A whole-brain voxel-based analysis was performed to assess differences in fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity across groups. Results: All three groups showed overlapping diffusion abnormalities in a network of tracts, including fornix, corpus callosum, posterior thalamic radiations, superior longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and uncinate fasciculus. Subtle regional differences were also observed across groups, with DAT particularly associated with degeneration of fornix and cingulum, lvPPA with left inferior fronto-occipital fasciculus and uncinate fasciculus, and PCA with posterior thalamic radiations, superior longitudinal fasciculus, posterior cingulate, and splenium of the corpus callosum. Conclusion: These findings show that while each AD phenotype is associated with degeneration of a specific structural network of white matter tracts, striking spatial overlap exists among the three network patterns that may be related to AD pathology.

The di‐2‐pyridylketone thiosemicarbazone Dp44mT is a metal‐chelating compound that has been demonstrated to have potent activity as an anticancer agent. Here we report that it also has a dramatic inhibitory effect on T‐cell activation in vitro. We found that 10 nM Dp44mT (IC 50 3.2 nM) prevented the up‐regulation of surface CD25, and completely suppressed the activation and proliferation of splenic T cells isolated from Mus musculus that were stimulated with either T‐cell receptor (TCR) cross‐linking antibodies or phorbol ester plus ionomycin. In contrast, Dp44mT had no adverse effects on the survival of resting T cells. In addition, T cells stimulated in the presence of Dp44mT maintained the ability to upregulate CD69 surface expression and secrete interleu‐kin‐2. Consistent with these observations, Dp44mT did not inhibit multiple canonical signals downstream of the TCR, including the nuclear factor of activated T cells. The effects of Dp44mT were easily mitigated by addition of nontoxic copper chelators or N ‐acetylcysteine, indicating a role for copper and reactive oxygen species in its actions. Together, these findings suggest that Dp44mT may serve as a potent immunosuppressive agent that could complicate its use as a cancer therapeutic agent, but might have utility in the treatment of autoimmunity.—Gundelach, J. H., Madhavan, A. A., Wettstein, P. J., Bram, R. J. The anticancer drug Dp44mT inhibits T‐cell activation and CD25 through a copper‐dependent mechanism. FASEB J. 27, 782–792 (2013). www.fasebj.org