Calcified Pseudoneoplasm of the Neuraxis (CAPNON)-A Rare Cause for Temporal Lobe Epilepsy: Not all Warrant a Surgical Intervention.

Epilepsy is a common neurological condition with varied etiological causes, with temporal lobe epilepsy being the most common. Among the varied etiologies of temporal lobe epilepsy, mesial temporal sclerosis is an important one and it presents as intractable epilepsy. However, we describe here a case of intractable temporal lobe epilepsy with a rather rare etiology, calcifying pseudo neoplasm of neuraxis (CAPNON) syndrome. CAPNON is a rare benign lesion that can occur anywhere in the central nervous system. The thought process till date is to excise any intracranial space occupying lesion to relieve pressure and for a better prognosis, which is not questionable. However, we feel in case of CAPNON, wait and watch protocol can be used to a better effect with radiological and clinical follow-up. Above all surgical excision was primarily done due to imaging confusion over CAPNON and this article comes up with few key findings to clinch the radiological diagnosis of CAPNON.

Genetic Prion Disease Caused by PRNP Q160X Mutation Presenting with an Orbitofrontal Syndrome, Cyclic Diarrhea, and Peripheral Neuropathy.

Patients with pathogenic truncating mutations in the prion gene (PRNP) usually present with prolonged disease courses with severe neurofibrillary tangle and cerebral amyloidosis pathology, but more atypical phenotypes also occur, including those with dysautonomia and peripheral neuropathy. We describe the neurological, cognitive, neuroimaging, and electrophysiological features of a 31-year-old man presenting with an orbitofrontal syndrome, gastrointestinal symptoms, and peripheral neuropathy associated with PRNP Q160X nonsense mutation, with symptom onset at age 27. The mutation was also detected in his asymptomatic father and a symptomatic paternal cousin; several members of prior generations died from early onset dementia. This is the first report of a family affected with the nonsense PRNP mutation Q160X displaying clear autosomal dominant disease in multiple family members and reduced penetrance. This case strengthens the evidence suggesting an association between PRNP truncating mutations and prion systemic amyloidosis. PRNP gene testing should be considered in any patient with atypical dementia, especially with early onset and neuropathy, even in the absence of a family history.

Adult-onset central nervous system hemophagocytic lymphohistiocytosis: a case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a clinical syndrome with both genetic and acquired causes characterized by elevated cytokine levels, hyperinflammation, and overactivation of lymphocytes and macrophages. It is typically a systemic disease with variable degrees of CNS involvement. Cases with predominantly central nervous system (CNS) involvement are very rare, with the vast majority of these occurring in infants and young children. This report documents a case of adult-onset CNS-HLH involving a middle-aged man. CASE PRESENTATION: A 55 year-old man developed progressive left hemiparesis and aphasia over the course of several months. Brain MRI showed multifocal, mass-like enhancing lesions with increased susceptibility consistent with blood products. An extensive workup for infectious, autoimmune, and neoplastic etiologies was significant only for a markedly elevated serum ferritin at 1456 ng/mL. Two brain biopsies showed a non-specific inflammatory process. The patient was treated empirically with steroids and plasmapheresis, but he continued to suffer a progressive neurological decline and died one year after onset of neurological symptoms. Autopsy revealed profound histiocytic infiltration, perivascular lymphocytosis, and emperipolesis, compatible with CNS-HLH. CONCLUSION: This case report describes an exceedingly rare presentation of an adult patient with CNS predominant HLH. This diagnosis should be considered in the differential diagnosis of adults presenting with progressive brain lesions, even in the absence of typical systemic signs of HLH.

Dual reinnervation of biceps muscle after side-to-side anastomosis of an intact median nerve and a damaged musculocutaneous nerve.

Traumatic peripheral nerve injury can lead to significant long-term disability for previously healthy persons. Damaged nerve trunks have been traditionally repaired using cable grafts, but nerve transfer or neurotization procedures have become increasingly popular because the axonal regrowth distances are much shorter. These techniques sacrifice the existing nerve pathway, so muscle reinnervation depends entirely on the success of the repair. Providing a supplemental source of axons from an adjacent intact nerve by using side-to-side anastomosis might reinnervate the target muscle without compromising the function of the donor nerve. The authors report a case of biceps muscle reinnervation after side-to-side anastomosis of an intact median nerve to a damaged musculocutaneous nerve. The patient was a 34-year-old man who had sustained traumatic injury primarily to the right upper and middle trunks of the brachial plexus. At 9 months after the injury, because of persistent weakness, the severely damaged upper trunk of the brachial plexus was repaired with an end-to-end graft. When 8 months later biceps function had not recovered, the patient underwent side-to-side anastomosis of the intact median nerve to the adjacent distal musculocutaneous nerve via epineural windows. By 9 months after the second surgery, biceps muscle function had returned clinically and electrodiagnostically. Postoperative electromyographic and nerve conduction studies confirmed that the biceps muscle was being reinnervated partly by donor axons from the healthy median nerve and partly by the recovering musculocutaneous nerve. This case demonstrates that side-to-side anastomosis of an intact median to an injured musculocutaneous nerve can provide dual reinnervation of the biceps muscle while minimizing injury to both donor and recipient nerves.

Discovery of GSK2656157: An Optimized PERK Inhibitor Selected for Preclinical Development.

We recently reported the discovery of GSK2606414 (1), a selective first in class inhibitor of protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), which inhibited PERK activation in cells and demonstrated tumor growth inhibition in a human tumor xenograft in mice. In continuation of our drug discovery program, we applied a strategy to decrease inhibitor lipophilicity as a means to improve physical properties and pharmacokinetics. This report describes our medicinal chemistry optimization culminating in the discovery of the PERK inhibitor GSK2656157 (6), which was selected for advancement to preclinical development.