Platelet Rich Plasma in the Treatment of Frontal Fibrosing Alopecia

Frontal Fibrosing Alopecia (FFA) represents a form of scaring alopecia more frequent in postmenopausal women that presents with frontal hairline recession. It is typically classified as a variant of lichen planopilaris. Treatment of FFA can be challenging with poor long-term outcomes. Platelet-Rich Plasma (PRP) consists of an autologous concentration of platelets in a small volume of plasma. Activated platelets secrete cytokines and growth factors and thus may have a potential role in the treatment of inflammatory scarring alopecia such as FFA. A 68-year-old female with multi-resistant FFA was treated with lesional PRP injections every 4 weeks for 16 weeks. Baseline LPPAI score and phototrichograms targeting a representative area of disease activity were compared at baseline and at 16 weeks. After 16 weeks, no significant change in follicular units or follicular density from baseline to week 16 was noted. Only a minimal improvement in inflammatory activity observed clinically and through the Lichen Planopilaris Activity Index was observed. The discordance between the follicular density count and observed inflammatory activity suggests a longer treatment and observational period is needed. Additionally, the frequency of PRP injections potentially may also need to be increased. Given the limited efficacy of current therapies for FFA, PRP injections may be an option in patients with refractory disease, as an adjunct to systemic therapy. Additional investigation is needed to optimize frequency of PRP injections in FFA and to better assess its true anti-inflammatory effect.

Cell-free DNA technologies for the analysis of brain cancer

Survival for glioma patients has shown minimal improvement over the past 20 years. The ability to detect and monitor gliomas relies primarily upon imaging technologies that lack sensitivity and specificity, especially during the post-surgical treatment phase. Treatment-response monitoring with an effective liquid-biopsy paradigm may also provide the most facile clinical scenario for liquid-biopsy integration into brain-tumour care. Conceptually, liquid biopsy is advantageous when compared with both tissue sampling (less invasive) and imaging (more sensitive and specific), but is hampered by technical and biological problems. These problems predominantly relate to low concentrations of tumour-derived DNA in the bloodstream of glioma patients. In this review, we highlight methods by which the neuro-oncological scientific and clinical communities have attempted to circumvent this limitation. The use of novel biological, technological and computational approaches will be explored. The utility of alternate bio-fluids, tumour-guided sequencing, epigenomic and fragmentomic methods may eventually be leveraged to provide the biological and technological means to unlock a wide range of clinical applications for liquid biopsy in glioma.

NCMP-19. RADIATION-INDUCED CRANIAL NEUROPATHY PRESENTING AS PROGRESSIVE BULBAR SYNDROME

Neuropathy is a well-known complication of radiation, especially when administered in proximity to the brachial plexus (BC), with symptoms usually appearing years after radiation. Pain is a less prominent feature when compared to neoplastic infiltration, with numbness and weakness being a more common and disabling complaint. Radiation-induced neuropathies tend to reach clinical stabilization after several months with por response to treatment. This is a case report of a 59 year-old Malaysian man who was diagnosed with nasopharyngeal carcinoma in 2002 treated with radiation to the nasopharynx in China. He has no evidence of disease to this date. In 2016 he started to develop progressive bulbar symptoms, such as hoarseness, hypophonia, and dysphagia. Symptoms worsened over the subsequent 18 months after presentation with clinical stabilization thereafter. Following the initial bulbar symptoms, he also developed bilateral hearing loss, atrophy of bilateral sternocleidomastoid muscles, significant tongue atrophy with fasciculations and tongue deviation. His clinical picture was consistent with bulbar amyotrophic lateral sclerosis. MRI brain and total spine did not show any intraparenchymal or nerve disease. An electromyography test was performed, which showed myokymia of the tongue and trapezius consistent with radiation-induced cranial neuropathy (CN). He received steroids without any clinical improvement, followed by hyperbaric oxygen with minimal improvement of his dysphagia, hoarseness and hypophonia. On last follow up his symptoms continued to be stable. Radiation to nasopharynx can cause radiation-induced CN with similar electromyographic findings to radiation-induced brachial plexopathy, such as myokymia. Symptoms can appear more than 10 years from radiotherapy, with progression over several months followed by clinical stabilization. Treatment with steroids, bevacizumab or hyperbaric oxygen only provide minimal benefit on this population.

Highly Active Multiple Sclerosis

A 16-year-old girl was evaluated for symptoms of thoracic myelitis with sensory loss below T12, gait difficulty, constipation, and incomplete bladder emptying. On evaluation, she had a flat affect, normal cranial nerve function, and normal motor examination findings. Deep tendon reflexes were symmetric, and plantar responses were flexor. She had a sensory level at T12 with diminished vibratory sense distal to the knees and normal coordination and gait. Magnetic resonance imaging of the brain, cervical spine, and thoracic spine showed a high burden of disease, with multiple enhancing lesions indicative of highly active disease. Spinal fluid analysis showed 16 white blood cells/µL with 95% lymphocytes; protein, 70 mg/dL; 7 unique oligoclonal bands; and immunoglobulin G index, 0.87. Neurocognitive testing showed normal scores overall, and psychiatric evaluation indicated major depressive disorder. She was given a diagnosis of relapsing-remitting multiple sclerosis, highly active. On initial evaluation for thoracic myelitis, intravenous methylprednisolone was given, with resolution of bladder and bowel symptoms and 75% recovery of sensory loss. High-dose interferon beta-1a was then initiated. At age 28 years, she had worsening left hemiparesis of 1 month’s duration. Neurologic examination showed word-finding difficulty, gaze-evoked horizontal nystagmus, moderate left-sided spastic hemiparesis in a pyramidal distribution, brisk reflexes with an extensor plantar response on the left, sensory ataxia in the left leg, and a hemiparetic gait. Intravenous methylprednisolone was given, with minimal improvement. She then received plasmapheresis with about 50% recovery of power. The patient was seropositive for antibodies to JC polyoma virus. Despite the increased risk of progressive multifocal leukoencephalopathy, natalizumab was reinitiated considering the even higher risk of long-term disability due to continued active disease (highly active multiple sclerosis). Her therapy was transitioned to teriflunomide. Six months later she returned with new right leg weakness and received high-dose intravenous corticosteroids for 5 days, followed by rituximab infusion. On follow-up neuroimaging, breakthrough disease activity was noted, and her therapy was switched to alemtuzumab. Highly active multiple sclerosis is characterized by frequent clinical episodes, with or without high disease activity on neuroimaging as evidenced by multiple enhancing lesions or interval new lesion formation, and disability accrual. It includes a spectrum of patients with clinical and radiologic evidence of ongoing disease activity who have no response to adequate treatment with multiple sclerosis disease-modifying therapy.

The possible protective role of Vitamin C versus Mesna against effect of Cyclophosphamide on the Urinary Bladder of Adult Male Albino Rats (A Histological and Immunohistochemical Study)

Background Cyclophosphamide (CYP) is considered one of the most successful chemotherapeutic drugs involved in anticancer regimens. However, it has multiple side effects. Mesna has an antiinflammatory effect and usually used in the treatment of cystitis. Vitamin C is a water-soluble vitamin which has a potent anti –oxidant effect that might protect cells against the oxidative damage caused by cyclophosphamide. Aim of the study The aim of the present study was comparing between the possible protective effect of vitamin C versus mesna and their combined therapy against the histological and immunohistochemical changes induced by cyclophosphamide on the urinary bladder of adult male albino rats. Material and methods Thirty adult male albino rats were divided into 5 groups, 6 rats each; (control(?), CYP-treated group (Пa), recovery group(Пb), mesna-treated group(???), vitamin C- treated group(?V) and the combined group (V). Histological examination of the H&Eand toluidine blue stained sections was done by light microscopy to assess the changes in the architecture of the urinary bladder. Avidin Biotin staining was performed for demonstration of iNOS immunoreactivity and histomorphometric analysis was done. Results Examination of H&E stained sections of cyclophosphamide- treated group (Пa) showed variable degrees of urothelial affection. Wide areas of urothelial cell degeneration with evident basal cytoplasmic vacoulatins, surface erosions and sloughed urothelial debris. Other Areas showed surface ulceration, completely denuded urothelium or the presence of multiple cysts replacing the urothelium and resting on the basement membrane. Semithin sections showed that the cytoplasmic microvesicles of umbrella cells were hardly detected. The Avidin Bioton stained sections showed intense positive immune reaction to iNOS in all layers of the urothelium. Scanning electron microscopy showed loss of the normal polygonal shape of the superficial epithelial cells, erosions, or deep ulcerations. Moreover, examination of the lamina propria by light microscopy showed multiple mononuclear inflammatory cells were detected, mast cells were seen in the lamina propria and some of them were invading the basement membrane of the urothelium. Dilated blood vessels and wide areas of extravasted blood (hemorrhage) were also observed. In addition, multiple epithelial cell nests of irregular shapes and sizes were deeply located in the lamina propria and exhibited pale esinophilic colloid discharge in their lumen. Scanning electron microscopy showed dense deposition of collagen fibers in both superficial and deep fibers of the lamina propria. Minimal improvement was observed in the recovery group (subgroup Пb). Mild to moderate improvement of the previous findings of CYP treated group was observed with each of mesna and vitamin C. Combined treatment of CYP with both of mesna and vitamin C induced apparent restoration of almost of the normal architecture of the urinary bladder. Conclusion CYP consumption developed morphologic and morphometric changes in the urinary bladder. The recovery group showed minimal improvement of the bladder architecture and increasing the period of recovery might produce better results. Each of vitamin C and mesna- treated groups induced mild to moderate improvement on the bladder architecture but treatment with combination of both of them offered remarkable improvement. Combined mesna and vitamin C induced significant protection via their combined anti-inflammatory and anti-oxidant proprieties.

Characterization of graphene-filled fluoropolymer coatings for condensing heat exchangers

Condensing heat exchangers are thermal devices subjected to extremely corrosive environments due to the formation of acidic condensates on the heat-exchange elements during service. To protect the heat exchangers from chemical attack, perfluoroalkoxy (PFA) coating has been applied as a barrier layer onto the surfaces of the heat-exchange elements to prevent corrosion. However, PFA has intrinsically poor thermal conductivity, and low wear resistance; thus, it is not naturally a good material for heat exchanger application. In this study, graphene nanoplatelets (GNPs) are incorporated into PFA powder as coating materials to improve the thermal properties of the fluoropolymer, for condensing heat exchangers application. Two grades of GNPs (8 nm and 60 nm layer thickness) are tested to evaluate the effect of graphene addition on the thermal, adhesion, electrical, and wear properties of the composites, which are compared to those mixed with multi-walled carbon nanotubes (MWCNTs). The results showed that both grades of GNPs significantly increased the thermal conductivity, i.e., ∼8× that of the virgin PFA. The composites incorporated with both grades of GNPs also demonstrated good coating adhesion strength and wear resistance, as well as excellent corrosion resistance. The composite filled with MWCNTs exhibited poor surface finish and minimal improvement in thermal performance.

TIO Associated with Hyperparathyroidism: A Rarity, a Rule, or a Novel HPT-PMT Syndrome—A Case Study with Literature Review

Objective. Association of primary hyperparathyroidism (pHPT) with phosphaturic mesenchymal tumors (PMT) is rarely reported. This report entertains the hypothesis of the causal association of HPT with tumor-induced osteomalacia (TIO) and of the existence of HPT-PMT syndrome. Case Presentation. A 49-year-old man presented with fragility rib fractures, generalized bone pain, and muscle weakness worsening over the past 3 years. Initial tests demonstrated hypophosphatemia and high PTH. The diagnosis of pHPT was entertained, but parathyroid scan was negative. During a 2-year follow-up, the patient reported minimal improvement of symptoms after intermittent treatment with calcitriol and phosphate. Biochemical evaluation showed persistent hypophosphatemia with renal phosphate wasting, elevated FGF23, and osteopenia on DXA scan. TIO was suspected. Multiple MRIs and whole-body FDG-PET scans were inconclusive. The patient subsequently underwent 68Ga-DOTATATE PET-CT, which revealed a somatostatin receptor-positive lesion in the lung. The resected mass was confirmed as PMT. The patient had dramatically improved symptoms, normal phosphate, calcium, and FGF23. During follow-up over 3 years postsurgery, the patient had slowly rising calcium and persistently elevated PTH. Conclusion. The debate whether the patient had pHPT or tertiary HPT prompted literature review showing that aberrant genes including FGFR1, FGF1, fibronectin 1, and Klotho were mechanistically involved in the HPT-PMT association. This case highlights the pitfalls contributing to delayed diagnosis and treatment of TIO and hypothesizes the association between pHPT and PMT.

Case of refractory delirious mania responsive to lithium

Delirious mania is an uncommon condition that is challenging to diagnose and treat. More often seen in patients with a history of bipolar disorder, it frequently presents with prominent catatonic features and overlaps with other diseases in the catatonic spectrum, such as neuroleptic malignant syndrome, serotonin syndrome and malignant catatonia. We present a case of delirious mania refractory to high doses of lorazepam, several antipsychotics and valproic acid, which responded dramatically to therapy with lithium after 26 days of minimal improvement with the other medications. The pathophysiology of delirious mania is reviewed, and the unique actions of lithium are discussed, highlighting possible reasons as to why lithium might offer advantages in the treatment of this disease.

Altitudinal Visual Field Defects Following Diagnostic Transfemoral Cerebral Angiography

Transfemoral cerebral angiography (TFCA) has been increasingly used as diagnostic method for the evaluation of cerebral vessels. Ophthalmologic complication after TFCA has rarely been reported, and most complications are associated with an intraoperative thrombo-embolic event. We reported a patient who developed a superior altitudinal visual field defect one day after diagnostic TFCA. The ophthalmic exam revealed a prominent inferior optic disc edema, and the fluorescein angiographic showed the non-perfusion of the corresponding inferior sectoral optic disc. Diffusion-weighted MRI on the day following cerebral angiography revealed multiple focal scattered acute infarctions. Even one month after steroid pulse therapy, the superior nasal field defect remained with minimal improvement. We believe this case was consistent with an acute anterior ischemic optic neuropathy (AION) due to thrombo-embolism after TFCA. Ophthalmic examinations and a visual field test should be performed before and immediately after the TFCA, particularly in the case with a high risk of thromboembolic events.

The Evaluation of Deformity Correction in Idiopathic Clubfoot During Ponseti Casting Sessions: Two Scoring Methods Depicted Graphically

Background We graphically analyzed the correction of total Pirani and Dimeglio scores and their subcomponents at sequential casting sessions for children with idiopathic clubfeet. Methods Correction of scores at weekly sessions was represented graphically. The tenotomy effect was accounted for separately. We classified 1st to 3rd casts as early, 4th and 5th cast midlevel, and beyond 5 as final casts to describe casting treatment. Results A total of 88 clubfeet (34 bilateral) in 54 patients were studied. Both total Pirani and Dimeglio graphs were characterized by a steep fall in early casts; subsequent minimal improvement in midlevel and final casts; later marked correction with tenotomy. Equinus in both scores stood as the most resistant deformity, showed full correction only following tenotomy. Dimeglio graphs captured coupling of various foot motions better over early casts than Pirani graphs. Conclusions Both Pirani and Dimeglio scores can adequately guide caregivers to progressive deformity correction in clubfoot. Keywords: Clubfoot, CTEV, Pirani, Dimeglio, Scores, Graphs