Newly Diagnosed Glioblastoma in Elderly Patients.

PURPOSE OF REVIEW: Elderly patients with newly diagnosed glioblastoma (eGBM) carry a worse prognosis compared with their younger counterparts. eGBM garners special attention due to the unique challenges, including increased treatment-associated toxicity, less relative benefit from aggressive therapy, medical comorbidities, and immunosuppression. The pivotal GBM trials excluded patients > 70 years old and the optimal treatment approach remains unsettled for eGBM. In this review, we analyze the historical evidence-based data for treating eGBM and discuss the future direction for managing this vulnerable population. RECENT FINDINGS: Treatment for eGBM continues to evolve. Therapy choice is guided by performance status and presence of O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation. For eGBM with good performance status, combinatorial hypofractionated radiation therapy (hRT) and temozolomide should be recommended. For those with poor performance status, further stratification based on MGMT promoter methylation test result is recommended. Single-agent temozolomide is a viable treatment option for MGMT methylated tumors (mMGMT); in particular, those classified with receptor tyrosine kinase II methylation. hRT alone can be considered in MGMT unmethylated (uMGMT) eGBM patients. As precision oncology continues to advance, effective targeted and immunotherapy may emerge as new treatment options for eGBM. Management of elderly patients with newly diagnosed GBM carries a unique set of challenges. Progress has been made in defining the optimal therapeutic approach for these patients, but many questions remain to be answered.

Approximal plaque pH lowering after sugar intake in a periodontally infected dentition.

OBJECTIVES: The aim of this study was to evaluate the effect of periodontal inflammation on the approximal plaque pH after a sucrose rinse. MATERIALS AND METHODS: Thirty-two periodontitis patients (aged 38-72 years; 9M/23F) were included. All patients were in need of periodontal surgery. Two non-adjacent interdental spaces, one healthy (no bleeding on probing [BoP] and probing pocket depth [PPD] < 4 mm) and one periodontally diseased (BoP and PPD ≥5 mm) were selected. Before and after surgery, the approximal plaque pH was measured before and after 2, 5 and 10 min after a 1-min rinse with sucrose solution. RESULTS: In periodontally diseased interdental spaces, a significant pH drop was seen 5 min after rinsing. In healthy spaces and after surgery, a significant pH drop was seen after 2 min. A multilevel regression analysis showed that greater probing pocket depths were significantly associated with pH change measured 5 min after rinsing (p < .05). Further on, the approximal pH drop after a sucrose rinse tended to be delayed in dentitions with ≥10% of PPD ≥5 mm (p = .052). CONCLUSIONS: The results suggest that an ongoing periodontal inflammation could temporarily neutralize acidic metabolic products after a sugar challenge. This may further suggest that plaque pH measured after a sugar rinse might be used to identify an ongoing periodontal disease.

Mucosal microflora in head and neck cancer patients.

OBJECTIVE: To analyse the tongue and buccal microflora prospectively in head and neck cancer patients treated with radiation therapy (RT). METHODS: In 33 dentate patients, microbial samples from the tongue and buccal mucosa were collected pretreatment, during treatment, and 6 months, 1 year and 2 years post-treatment. Microorganisms associated with oral health and oral disorders were analysed using cultivation technique. Oral mucositis was scored at the appointment during treatment. RESULTS: Compared with pretreatment, lactobacilli and Candida increased on the tongue, while streptococci and Neisseria decreased during treatment. Two years post-treatment, Neisseria and Prevotella were decreased and Candida increased. On the buccal mucosa, an increased growth of lactobacilli and increased detection frequencies of the opportunistic bacteria Staphylococcus aureus, Gram-negative enteric rods and enterococci were seen during treatment compared with pretreatment. Seventy per cent showed severe mucositis during treatment. Two years post-treatment the total count as well as streptococci, Neisseria and Fusobacterium nucleatum were decreased and lactobacilli increased compared with pretreatment. CONCLUSION: Despite improvements in treatment for cancer in the head and neck region, microorganisms associated with oral health decrease during treatment and mucosal pathogens increase. Two years post-treatment, levels of acid-tolerant (lactobacilli and Candida) were increased, while acid-sensitive microorganisms (Neisseria and F. nucleatum) were decreased, plausibly due to persisting decreased salivary secretion rate.

Explorative study on mucosal and major salivary secretion rates, caries and plaque microflora in head and neck cancer patients.

OBJECTIVE: To analyse mucosal and major salivary secretion rates, caries and plaque microflora in connection with treatment for cancer in the head and neck region. METHODS: Thirty-three patients were included and the number of teeth, filled surfaces and caries lesions registered. The labial and buccal gland secretion and stimulated whole salivary secretion rates were determined. Supragingival plaque microflora was analysed using cultivation technique. Data were collected pretreatment, during treatment and 6 months, 1 year and 2 years post-treatment. RESULTS: Two years post-treatment, 36% had new caries lesions, which had been restored. The labial secretion was comparable with pretreatment, while the buccal secretion was lower (P < .001). The stimulated secretion rate was lower compared with pretreatment (P < .001) and was ≤0.7 mL/minute for 50%. Growth of lactobacilli increased during treatment (P < .001) and remained increased (P < .001), while growth of mutans streptococci was decreased (P < .01) 2 years post-treatment. Growth of Candida increased over time and was higher 2 years post-treatment compared with pretreatment (P < .001) while growth of Prevotella was lower (P < .01). CONCLUSIONS: Two years post-treatment, the stimulated salivary secretion rate was substantially decreased, acid-tolerant lactobacilli and Candida increased, acid-sensitive microorganisms decreased, and the caries prevalence was low.

Primary Ocular Adnexal Extranodal Marginal Zone Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma Presenting as Orbital Apex Syndrome.

A 75-year-old female with a past medical history significant for prior stroke and atrial fibrillation presented with acute onset of orbital apex syndrome with chemosis and periorbital ecchymosis. Following initial treatment to relieve intraocular pressure, she began spontaneously haemorrhaging retro-orbitally. Preliminary investigation with neuroimaging demonstrated a left orbital mass with extension into the orbital apex. A provisional diagnosis of cavernous haemangioma was made. She was treated with transorbital resection of the orbital mass. Subsequent histopathology revealed a diagnosis of ocular adnexal non-Hodgkin lymphoma of histologic type extranodal marginal zone of mucosa-associated lymphoid tissue (MALT lymphoma). MALT lymphoma should be considered in cases of orbital apex syndrome.

Using the Theories of Joseph Babinski to Manage Functional Vision Loss.

OBJECTIVE: To report our use of persuasion to treat patients with functional vision loss and to place them in the context of both Joseph Babinski's theories on hysteria and the current literature on management of functional vision loss. BACKGROUND: Conversion disorders, such as functional vision loss, can develop in response to a traumatic event. Recent functional imaging studies have found that, rather than being malingerers, patients with conversion disorders show changes within neuromodulatory pathways, suggesting organic dysfunction rather than a purely psychological disorder. METHODS: We conducted a retrospective analysis of 8 consecutive patients (7 female, 1 male; mean age 16 years) who had presented to a university-based neuro-ophthalmology clinic with vision loss from a conversion disorder. The patients had been given a lengthy visual task to perform at home, with the suggestion that their vision would improve by the time they completed the task. RESULTS: All 8 patients had evidence of a dissociation between real and perceived visual acuity and fields. All the patients performed the assigned visual task at home, and all either reported improvement or showed improved visual function at follow-up. CONCLUSIONS: A century after Joseph Babinski proposed using persuasion in managing patients with vision loss from a conversion disorder, we report that his method remains a viable and pathophysiologically sound option. Future case-controlled studies that include functional magnetic resonance imaging, other neurophysiologic imaging, and neuroradiographic evaluation may strengthen the correlation between persuasion therapy and recovery of normal vision.

A non-enhancing, T2 fluid-attenuated inversion recovery hyperintense, diffusion-restricting brainstem lesion in an EGFR tyrosine kinase inhibitor-treated non-small-cell lung cancer patient.

Leptomeningeal metastasis (LM) is a devastating complication of malignancy. Diagnosis relies on both contrast enhancement on imaging and malignant cells in cerebral spinal fluid cytology. Though early detection and prompt intervention improves survival, the detection of LM is limited by false negatives. A rare brainstem imaging finding uncovered specifically in EGFR mutation-positive lung cancer patients may represent an early sign of LM. This sign demonstrates high signal on T2 fluid-attenuated inversion recovery and diffusion-weighted imaging sequences, but paradoxically lacks correlative contrast enhancement. Here we report a case of a 72-year-old female EGFR-positive lung cancer patient who developed this lesion following treatment with two first-generation EGFR tyrosine kinase inhibitors then showed subsequent response to osimertinib, an irreversible third-generation EGFR tyrosine kinase inhibitor.

A non-enhancing, T2 FLAIR hyperintense, diffusion-restricting brainstem lesion in an EGFR-positive lung cancer patient may represent an early indicator of leptomeningeal metastases.

Pembrolizumab in an HIV-infected patient with glioblastoma.

Persons living with human immunodeficiency virus (PLWH) carry increased risk for developing malignancies, including glioblastoma. Despite extensive investigations, both human immunodeficiency virus (HIV) and glioblastoma are incurable. Treatment for a patient with combined glioblastoma and HIV remains an unexplored need. Preliminary evidence suggests that immunotherapy may be effective for the simultaneous treatment of both HIV and cancer by reversing HIV latency and T cell exhaustion. We present a case of glioblastoma in a PLWH who was treated with pembrolizumab. Treatment was well tolerated and safe with a mixed response. Our patient did not develop any opportunistic infections, immune-related adverse events, or worsening of his immunodeficiency. To our knowledge, this is the first reported case of a PLWH and glioblastoma treated with immunotherapy.

Persons living with human immunodeficiency virus (PLWH) are at increased risk for cancers, including glioblastoma. Despite extensive research, both human immunodeficiency virus (HIV) and glioblastoma are incurable. The optimal treatment for concurrent HIV and glioblastoma is unknown. Early evidence suggests that immunotherapy can deplete residual HIV and restore immune function. We present a case of glioblastoma in a PLWH treated with immunotherapy. Treatment was well tolerated and safe. To our knowledge, this is the first reported case of a PLWH and glioblastoma treated with immunotherapy.

Metastatic glioblastoma to the lungs: a case report and literature review.

Glioblastoma is the most common malignant primary brain tumor. Despite its infiltrative nature, extra-cranial glioblastoma metastases are rare. We present a case of a 63-year-old woman with metastatic glioblastoma in the lungs. Sarcomatous histology, a reported risk factor for disseminated disease, was found. Genomic alterations of TP53 mutation, TERT mutation, PTEN mutation, and +7/-10 were also uncovered. Early evidence suggests these molecular aberrations are common in metastatic glioblastoma. Treatment with third-line lenvatinib resulted in a mixed response. This case contributes to the growing body of evidence for the role of genomic alterations in predictive risk in metastatic glioblastoma. There remains an unmet need for treatment of metastatic glioblastoma.

Glioblastoma is the most common malignant primary brain tumor. Glioblastoma can spread into healthy tissue, but metastases beyond the brain are rare. We present a case of a 63-year-old woman with metastatic glioblastoma in the lungs. We identified risk factors associated with spread beyond the brain, including factors related to tissue structure and specific molecular alterations. Treatment with third-line lenvatinib resulted in a mixed response. This case adds to the limited existing data for the use of molecular alterations to serve as risk factors for metastatic glioblastoma. Treatment options are needed for this devastating disease.

Dabrafenib and steroids for the treatment of Erdheim-Chester disease with extensive CNS involvement: a case report.

Erdheim-Chester disease (ECD) is an exceedingly rare non-Langerhans cell CD68+ CD1a- S100- histiocytic multi-organ disease. Diagnosis of ECD is often delayed due to non-specific radiographic findings and heterogeneous lesional tissue. Increasingly, the role of genomic alterations is being recognized for both diagnosis and treatment of ECD. More than half of ECD patients harbor the BRAFV600E mutation. Evaluation for this mutation be can falsely negative on immunohistochemical staining and confirmation with molecular analyses is recommended. We present a case of the 44 year-old male with BRAFV600E-positive ECD treated successfully with steroids followed by single-agent dabrafenib.

Erdheim-Chester disease (ECD) is an exceedingly rare type of histiocytosis (a disorder of white blood cells). The diagnosis of ECD can be challenging because tissue biopsy may not provide a definitive diagnosis. Currently, genetic mutations can be used to support both diagnosis and treatment. We present a case of the 44 year-old male with BRAF V600E -positive ECD who was treated successfully with steroids followed by dabrafenib.

Axicabtagene Ciloleucel in Patients Ineligible for ZUMA-1 Because of CNS Involvement and/or HIV: A Multicenter Experience.

Secondary central nervous system lymphoma (SCNSL) is associated with poor prognosis and new therapeutic approaches are needed. The pivotal trial that led to US Food and Drug Administration (FDA) approval of axicabtagene ciloleucel excluded patients with SCNSL and human immunodeficiency virus. In this multi-institutional retrospective study, 14 SCNSL patients treated with axicabtagene ciloleucel, 3 of whom had human immunodeficiency virus, experienced rates of severe neurotoxicity and complete response of 32% and 58%, respectively. This is similar to rates observed in the pivotal ZUMA-1 trial that led to the approval of axi-cel at median follow-up of 5.9 months. Chimeric antigen receptor T-cell therapy is potentially a life-saving therapy for SCNSL patients and should not be withheld.

Metal-ion susceptibility of oral bacterial species.

AIMS: This study aimed to evaluate the effect of lead (Pb) on growth of bacterial species related to dental diseases in vitro. METHODS AND RESULTS: The effects of lead acetate on representative species of the oral flora were examined at 0.1-10 mmol l(-1) and compared with the effect of silver nitrate and ferrous sulfate. The minimal inhibitory concentration of lead acetate was between 0.15 and 5 mmol l(-1) for the bacterial strains tested. The minimal bactericidal concentration of lead acetate for most oral species was detected in the range of 5-10 mmol l(-1). Silver nitrate at a concentration of 1.25 mmol l(-1) was sufficient to exhibit antibacterial activity against almost all bacteria tested. Ferrous sulfate had the lowest effect. CONCLUSIONS: The study indicated a general antimicrobial effect of lead on oral bacterial species in the range of 0.15-10 mmol l(-1). The toxicity of silver nitrate was the highest, whereas that of ferrous sulfate was the lowest. Gram-positive species had a tendency to be less susceptible for metals than Gram-negatives. SIGNIFICANCE AND IMPACT OF THE STUDY: The study shows that it is possible that microbiological changes may occur in the dental plaque in children because of toxic exposure of environmental lead.

Asymptomatic brainstem lesions and pachymeningeal enhancement after anti-PD-1 therapy.

Neurological immune-related adverse events (irAEs) are rare toxicities that occur following immune checkpoint inhibitor therapy. We propose that patients with thymic malignancies and graft-versus-host disease (GVHD) are predisposed to irAEs. We present two asymptomatic patients, one with thymoma and another with GVHD, who developed abnormal brain MRIs after treatment with programmed cell death protein 1 inhibitors. The first patient, with thymic cancer and thymoma, developed pontine enhancing MRI lesions following treatment with pembrolizumab. The second patient, with prior GVHD, developed pachymeningeal enhancement following treatment with nivolumab. IrAEs with abnormal MRI studies, despite asymptomatology, have significant impact on the treatment strategy for these patients.

Severity of Downgaze Palsy in the Context of Disease Duration Could Estimate Survival Duration in Patients With Progressive Supranuclear Palsy.

It is an unmet need to estimate survival duration for patients with progressive supranuclear palsy (PSP). The objective of this study was to identify factors associated with the survival duration in patients with PSP. We followed up 23 patients with probable PSP-RS (Richardson syndrome) or PSP-P (parkinsonism) in our PSP center until death from 2011 to 2019. We prospectively and quantitatively rated their downgaze palsy whenever first noticed in our clinic. This was utilized along with the disease duration, motor function, medication use for parkinsonism, sex, age at onset of PSP, comorbid pulmonary and cardiovascular diseases, and the total survival duration from the onset of PSP to death for prediction analysis. A well-fitted linear regression model and a multivariant Cox model were applied to identify predicting factors for total survival duration. All patients had the specific hummingbird sign on brain MRI for PSP when downgaze palsy was documented. We found that the severity of downgaze palsy and the disease duration at the assessment were consistently correlated with the total survival duration in both models. The total survival duration could be further estimated by a formed regression equation. We conclude that severity and time to develop downgaze palsy could help to estimate the total survival duration in patients with probable PSP-RS and PSP-P, the major forms of PSP, which has significant clinical applications in clinical counseling and trial enrollment.

An atypical presentation of primary central nervous system lymphoma: A case report.

RATIONALE: Primary central nervous system lymphoma (PCNSL) involving the choroid plexus is exceedingly rare. The differential diagnosis for choroid plexus enhancing lesions in addition to lymphoma includes infections, sarcoidosis, tuberculosis, papilloma, meningioma, subependymoma, and metastatic lesions. PATIENT CONCERNS: A 71-year-old man presented with 3 days of episodic memory loss and gait disturbance. Brain magnetic resonance imaging showed homogenously enhancing lesions with mildly restricted diffusion and T2 hypointensity in the lateral ventricles, as well as T2 hyperintensity and enhancement in the right hippocampus. His episodic memory loss was thought to be secondary to subclinical focal seizures, supported by EEG revealing right temporal lobe epileptiform discharges. DIAGNOSES: Large B-cell lymphoma, nongerminal center type was revealed on pathological examination. INTERVENTIONS: Stereotactic biopsy of his right thalamic lesion was performed. OUTCOMES: The patient underwent induction therapy with high-dose methotrexate, temozolomide, and rituximab, which resulted in complete resolution of the enhancing lesions. He then underwent conditioning chemotherapy with carmustine and thiotepa, followed by autologous stem cell transplantation. His PCNSL remains in remission 42 weeks after the onset of symptoms. LESSONS: We report a patient with multifocal PCNSL involving the choroid plexus, who presented with abnormal gait and episodic confusion and memory loss. PCNSL should be considered in the differential diagnosis of acute encephalopathy among immunocompetent older individuals who have choroid plexus enhancing lesions.

A retrospective study on the microbiology in patients with oral complaints and oral mucosal lesions.

OBJECTIVE: The aim of this study was to microbiologically analyze oral mucosal samples collected during 2 years from patients with oral mucosal complaints. MATERIALS AND METHODS: Mucosal scraping samples were taken from 297 patients and semiquantified by culture for detection of opportunistic microorganisms e.g. Staphylococcus aureus, enterococci, aerobic Gram-negative bacilli (AGNB) and yeasts. Antibiotic susceptibility test was performed. RESULTS: Altogether 297 patients were sampled (mean age 56.8 +/- 20.7). Among the 110 patients with known medical condition, 48 were systemically immunocompromised, 35 had systemic diseases, and 27 had only local oral complaints. Opportunists in moderate growth or more were present commonly in all three groups and most frequent in the immunocompromised patients (66.7%). Candida species were the most frequent opportunist (68.8%), however, their level was low and combinations with bacterial opportunists were common (39.6%). All bacterial opportunists tested were antibiotic multiresistant. Follow-up samples were collected in 23 cases out of which seven showed still presence of opportunists in heavy growth despite repeated treatment with ciprofloxacin. CONCLUSIONS: This study showed a frequent presence of bacterial and fungal opportunists in patients with oral mucosal complaints, which were most common in immunocompromised individuals, however, also frequent in patients with local oral complaints only. Systematic evaluation of different treatment strategies is needed.

Anomalies of left coronary artery origin affecting surgical repair of hypoplastic left heart syndrome and Shone complex.

There has traditionally been less concern regarding coronary anomalies with left-sided congenital heart lesions such as hypoplastic left heart syndrome (HLHS)or Shone complex than with other lesions. However, coronary anomalies in this setting can profoundly affect surgical intervention, particularly when surgical repair involves the ascending aorta. We describe four patients with congenital left-sided heart lesions in which left coronary artery (LCA) anomalies substantially affected intervention and outcome. In the first two cases, the coronary anomalies were not identified prospectively and resulted in surgical injury directly to the coronary or to its surrounding region. In the latter two cases, successful identification of the coronary anomaly preoperatively allowed for modification of surgical technique and/or intervention. We conclude that detailed coronary artery assessment should be part of the routine echocardiographic evaluation of congenital left-sided heart lesions that require surgery.

Eyes and stroke: the visual aspects of cerebrovascular disease.

A large portion of the central nervous system is dedicated to vision and therefore strokes have a high likelihood of involving vision in some way. Vision loss can be the most disabling residual effect after a cerebral infarction. Transient vision problems can likewise be a harbinger of stroke and prompt evaluation after recognition of visual symptoms can prevent future vascular injury. In this review, we discuss the visual aspects of stroke. First, anatomy and the vascular supply of the visual system are considered. Then, the different stroke syndromes which involve vision are discussed. Finally, topics involving the assessment, prognosis, treatment and therapeutic intervention of vision-specific stroke topics are reviewed.

Cardiac dysfunction in hypertrophic cardiomyopathy mutant tropomyosin mice is transgene-dependent, hypertrophy-independent, and improved by beta-blockade.

Familial hypertrophic cardiomyopathy (FHC) has been linked to mutations in proteins of the cardiac contractile apparatus, including alpha-tropomyosin (Tm). Mice expressing alphaTm in the heart were developed to determine the effects of FHC mutant Tm on cardiac structure and function from single cardiac myocytes to whole organ function in vivo. Expression of E180G mutant Tm did not produce cardiac hypertrophy or detectable changes in cardiac muscle morphology. However, E180G mutant Tm expression increased the Ca2+ sensitivity of force production in single cardiac myocytes in a transgene expression-dependent manner. Contractile dysfunction in single myocytes manifested organ level dysfunction, as conductance-micromanometry showed E180G Tm mice had significantly slowed relaxation (diastolic dysfunction) under physiological conditions. The diastolic dysfunction in E180G Tm mice was no longer evident during beta-blockade because propranolol eliminated the effect of E180G Tm to slow myocardial relaxation. Cellular and organ level dysfunction were evident in E180G Tm mice in the absence of significant cardiac structural abnormalities normally associated with FHC. These findings therefore suggest that diastolic dysfunction in FHC may be a direct consequence of FHC mutant protein expression. In addition, because diastolic dysfunction in E180G Tm mice is dependent on inotropic status, cardiovascular stress may play an important role in FHC pathogenesis.