Recurrent Spontaneous Paresthesia in the Upper Limb Could Be Due to Migraine: A Case Series

Transient neurologic dysfunction is a characteristic feature of migraine. About 20% of migraineurs may experience various symptoms in the absence of any headache at one time or another. Visual auras are the most common auras of migraine, and migraine is considered as the most common cause of transient vision loss in young patients. Sensory auras are the second most common migrainous auras. However, the literature is silent for isolated sensory aura as a migraine equivalent. Herein we report 14 patients with recurrent episodic paresthesia in the limbs and other body parts. All patients fulfilled the diagnostic criteria of “typical aura without headache” of ICHD‐3β. All patients were subjected to various investigations to rule out secondary causes. Ten patients received antimigraine drugs and all showed a positive response to therapy. Recurrent spontaneous paresthesia is quite common in the general population and many patients remain undiagnosed. We speculate that a subset of patients might be related to migrainous sensory auras.     

Parkin cooperates with GDNF/RET signaling to prevent dopaminergic neuron degeneration

Parkin and the glial cell line–derived neurotrophic factor (GDNF) receptor RET have both been independently linked to the dopaminergic neuron degeneration that underlies Parkinson’s disease (PD). In the present study, we demonstrate that there is genetic crosstalk between parkin and the receptor tyrosine kinase RET in two different mouse models of PD. Mice lacking both parkin and RET exhibited accelerated dopaminergic cell and axonal loss compared with parkin-deficient animals, which showed none, and RET-deficient mice, in which we found moderate degeneration. Transgenic expression of parkin protected the dopaminergic systems of aged RET-deficient mice. Downregulation of either parkin or RET in neuronal cells impaired mitochondrial function and morphology. Parkin expression restored mitochondrial function in GDNF/RET-deficient cells, while GDNF stimulation rescued mitochondrial defects in parkin-deficient cells. In both cases, improved mitochondrial function was the result of activation of the prosurvival NF-κB pathway, which was mediated by RET through the phosphoinositide-3-kinase (PI3K) pathway. Taken together, these observations indicate that parkin and the RET signaling cascade converge to control mitochondrial integrity and thereby properly maintain substantia nigra pars compacta dopaminergic neurons and their innervation in the striatum. The demonstration of crosstalk between parkin and RET highlights the interplay in the protein network that is altered in PD and suggests potential therapeutic targets and strategies to treat PD.     

Anti-inflammatory and anti-arthritic effects of 3-hydroxy, 2-methoxy sodium butanoate from the leaves of Clerodendrum phlomidis L.f.

Introduction

The leaves of Clerodendrum phlomidis L.f. have been used in the Indian traditional system of medicine to treat several inflammatory diseases and arthritis. The aim of the present study was to assess the anti-inflammatory and anti-arthritic activities of the leaves of C. phlomidis and to isolate the active principle by bioactivity guided fractionation.

Materials and methods

To find the anti-inflammatory constituents from this plant, fractionations were performed with concurrent bioassays. Carrageenan-induced inflammation and Freund complete adjuvant (FCA)-induced arthritic rat models were used. The anti-inflammatory and anti-arthritic activities of the isolated compound were studied by assessing the histology of the joints, levels of lysosomal enzymes, protein-bound carbohydrates, acute phase protein, etc., in plasma, as well as by estimating the levels and expression of pro-inflammatory cytokines in the joints.

Results

Repeated fractionations and bioassays yielded a novel bioactive compound: 3-hydroxy, 2-methoxy-sodium butanoate. Treatment with this compound reduced the paw edema induced by carrageenan and FCA dose dependently. The levels of lysosomal enzymes and protein-bound carbohydrates decreased significantly upon treatment with the compound. The level of plasma acute phase protein was also decreased compared with control animals. Protein levels and mRNA expression of pro-inflammatory cytokines TNF, IL-1 and IL-6 in the joints were decreased significantly in a dose-dependent manner and the histopathological data also added evidence of the anti-arthritic property of the compound.

Conclusion

The 3-hydroxy,2-methoxy sodium butanoate isolated from plant leaves displays considerable potency in anti-inflammatory action and has a prominent anti-arthritic effect. This is the first report of this natural compound with bioactivity.