Bilateral Deep Brain Stimulation of the Ventral Intermediate Nucleus of the Thalamus Improves Objective Acoustic Measures of Essential Vocal Tremor.

BACKGROUND AND OBJECTIVES: Deep brain stimulation of the ventral intermediate nucleus of the thalamus (VIM-DBS) is an established treatment for medically refractory essential tremor. However, the effect of VIM-DBS on vocal tremor remains poorly understood, with results varying by method of vocal tremor assessment and stimulation laterality. This single-center study measures the effect of bilateral VIM-DBS on essential vocal tremor using blinded objective acoustic voice analysis. METHODS: Ten patients with consecutive essential tremor with comorbid vocal tremor receiving bilateral VIM-DBS underwent voice testing before and after implantation of DBS in this prospective cohort study. Objective acoustic measures were extracted from the middle one second of steady-state phonation including cepstral peak prominence, signal-to-noise ratio, percentage voicing, tremor rate, extent of fundamental frequency modulation, and extent of intensity modulation. DBS surgery was performed awake with microelectrode recording and intraoperative testing. Postoperative voice testing was performed after stable programming. RESULTS: Patients included 6 female and 4 male, with a mean age of 67 ± 6.7 years. The VIM was targeted with the following coordinates relative to the mid-anterior commissure:posterior commissure point: 13.2 ± 0.6 mm lateral, 6.2 ± 0.7 mm posterior, and 0.0 mm below. Mean programming parameters were amplitude 1.72.0 ± 0.6 mA, pulse width 63.0 ± 12.7 µs, and rate 130.6 ± 0.0 Hz. VIM-DBS significantly improved tremor rate from 4.43 ± 0.8 Hz to 3.2 ± 0.8 Hz (P = .001) CI (0.546, 1.895), jitter from 1 ± 0.94 to 0.53 ± 0.219 (P = .02) CI (-0.124, 1.038), cepstral peak prominence from 13.6 ± 3.9 to 18.8 ± 2.9 (P = .016) CI (-4.100, -0.235), signal-to-noise ratio from 15.7 ± 3.9 to 18.5 ± 3.7 (P = .02) CI (-5.598, -0.037), and articulation rate from 0.77 ± 0.2 to 0.82 ± .14 (P = .04) CI (-0.097, 0.008). There were no major complications in this series. CONCLUSION: Objective acoustic voice analyses suggest that bilateral VIM-DBS effectively reduces vocal tremor rate and improves voicing. Further studies using objective acoustic analyses and laryngeal imaging may help refine surgical and stimulation techniques and evaluate the effect of laterality on vocal tremor.

Fecal Microbiota Transplant in Recurrent Clostridium Difficile Infections: A Systematic Review.

Fecal Microbiota Transplantation (FMT) is the process of transferring the fecal microbiome from a healthy donor to an individual with repeated multiple episodes of Clostridium difficile infection. It is also known as stool transplant. Fecal microbiota transplant is effective and safe in various studies, the approval from the Food and Drug Administration (FDA) remains pending. The main objective of this systemic review is to evaluate the efficacy and safety of stool transplant in studies with only treatment groups (FMT) and studies with treatment (FMT) and antibiotic (AB) groups and previous studies. Online databases PubMed, PubMed Central, Science Direct, Google Scholar, and Embase were searched for relevant articles in the last five years (2016 to 2021) using automation tools. Following the removal of duplicates, screening of eligibility criteria, titles/abstracts, and quality appraisal were done by two authors independently. In total, seven observational studies are in this review article. Out of the seven observational studies, five are retrospective and two prospective. Two of the five retrospective and one of two prospective studies have a control group. In both the prospective studies and one retrospective study, FMT efficacy of (68% to 93%) was demonstrated in the elderly population despite high index comorbidities. In the younger individuals with inflammatory bowel disease, and efficacy of 90% or above was found. The most common side effects were minor such as fever, abdominal pain, bloating, and flatulence. In one study, two cases of aspiration events occurred attributed to the gastroscopy route of donor feces delivery. There was no statistical significance in the incidence of diseases such as (allergies, autoimmune diseases, cancer, inflammatory bowel diseases, and neurological diseases like dementia and migraine).  Fecal microbiota transplantation has shown to be effective and safe in recurrent Clostridium difficile infections. Since very few pragmatic studies have demonstrated its efficacy and safety, their application is not well established. Robust studies, both observation and experiment, are required in the future to well-establish its effectiveness, safety in the treatment of recurrent Clostridium difficile infection.

Case Report: Novel Anchoring Technique and Surgical Nuances for Trigeminal Ganglion Stimulation in the Treatment of Post-Herpetic Trigeminal Neuropathic Facial Pain.

Introduction: Trigeminal ganglion stimulation is a neuromodulatory surgical procedure utilized to treat trigeminal neuropathic pain. This technique involves the placement of a stimulating electrode adjacent to the trigeminal ganglion and can be trialed before permanent implantation. Wider adoption by surgical practitioners is currently limited by complications such as lead migration from the trigeminal ganglion, which can result in loss of therapy and cannot be rectified without repeat surgery. We describe a novel surgical modification that successfully anchors the trigeminal ganglion electrode long-term. Objective: To describe a novel surgical technique for the anchoring of trigeminal ganglion stimulation electrodes and a case report of a patient with post-herpetic trigeminal neuropathic pain treated with this approach. Methods: An electrode was inserted percutaneously through the foramen ovale into Meckel's cave, adjacent to the trigeminal ganglion. The lead was anchored using a modification of an existing anchoring device, which was inserted into the buccal incision. The lead was connected to a generator for therapeutic stimulation. The location of the lead was followed radiographically using serial lateral skull radiographs. Results: A 74-year-old male with post-herpetic trigeminal neuropathic pain, who had failed prior surgical therapies, underwent trigeminal ganglion stimulation. The trial lead was anchored using standard techniques and migrated outward within 7 days, rendering the trial electrode ineffective. The permanent lead was anchored using the described novel technique and remained in position without clinically significant outward migration nor loss in targeted stimulation until the last follow-up at 6 months. Conclusion: Trigeminal ganglion stimulation is an effective therapeutic option for medically refractory trigeminal neuropathic pain. The novel surgical adaptation described prevents the outward migration of the lead and enables stable long-term lead placement.

Soybean-Oil Lipid Minimization for Prevention of Intestinal Failure-Associated Liver Disease in Late-Preterm and Term Infants With Gastrointestinal Surgical Disorders.

BACKGROUND: Intestinal failure-associated liver disease (IFALD), a multifactorial disease, is common among infants with gastrointestinal surgical disorders (GISDs). Prolonged soy-based intravenous lipid emulsion (S-ILE) intake is associated with IFALD, but preventive studies of limiting S-ILE have been inconclusive. Furthermore, a double-blind, randomized preventive trial (DBRPT) of S-ILE intake has not been performed in infants with GISDs. Our objective was to compare the effect of 1 g/kg/d vs 2 g/kg/d S-ILE intake for 6 weeks on the incidence of IFALD and the rate of rise of direct bilirubin (DB) in infants with GISDs. METHODS: A DBRPT was conducted in infants with GISDs at ≥34 weeks' gestational age (GA) admitted to the NICU within 72 hours after birth. Infants were randomized in a 1:1 ratio to receive either 1 or 2 g/kg/d S-ILE for 6 weeks. IFALD was defined as DB ≥2 mg/dL. RESULTS: Forty infants were studied. The 2 groups had similar clinical characteristics except for GA and blood group incompatibility. Thirty percent of infants in each group developed IFALD (P = .94). However, infants in the group receiving 1 g/kg/d S-ILE (n = 20) had a lower rate of rise of DB compared with infants in the group receiving 2 g/kg/d S-ILE (n = 20). CONCLUSIONS: Reducing S-ILE intake for 6 weeks in infants with GISD at ≥34 weeks' GA may not prevent IFALD. The extrapolated data on the rate of rise of DB suggest a possible risk of earlier development of IFALD with S-ILE intake of 2 g/kg/d, as compared with 1 g/kg/d, beyond the 6-week study period.

Programming Parameters and Techniques in Trigeminal Ganglion Stimulation for Intractable Facial Pain.

OBJECTIVES: Atypical facial pain syndromes are challenging disorders to manage and often incur limited benefit with surgery for classical trigeminal neuralgia presentations, such as microvascular decompression or ablative procedures. Neurostimulation of the trigeminal ganglion and peripheral nerves can be effective at treating atypical presentations of trigeminal facial pain affecting the V1-3 dermatomes, and the surgical techniques are well described. The stimulation parameters, however, have thus far received limited description; we therefore sought to describe programming strategies. MATERIALS AND METHODS: We performed a retrospective chart review, examining patients that underwent trigeminal ganglion stimulation (TGS) and nerve branch stimulation for atypical facial pain and trigeminal neuropathic pain, and describe the programming strategies in detail. RESULTS: We describe the use of high-frequency stimulation (1000 Hz), with alteration in pulse width (60-220 msec) and amplitude (0.5-3 V) to achieve effective treatment of refractory trigeminal facial pain. These parameters differ from existing published parameters for trigeminal nerve branch stimulation. We also describe the programming of specific contacts on each lead to target specific aspects of the individual patients' facial pain. CONCLUSIONS: The use of effective programming strategies is critical to the success of neurostimulation surgical treatments; however, the critical details in programming strategies typically receive limited description. We report on the use of several successful programming strategies for TGS, to assist pain providers in successfully applying these surgical techniques in these difficult to manage atypical facial pain syndromes.

Retrospective Analysis of Subtarsal Incision in Maxillofacial Trauma.

INTRODUCTION: Subciliary, subtarsal and infraorbital incisions are the conventional cutaneous approaches to infraorbital rim and floor. MATERIALS AND METHODS: A retrospective study was developed with 30 patients reviewed over a period of 12 months. RESULT: No cases showed ectropion in minimum 12-month follow-up. Mild scleral show was present in 3 cases. At the end of 12 months, scar was invisible in 25 patients, mild in 4 patients and moderate in 1 patient who developed wound infection. CONCLUSION: Subtarsal incision shows good result with very minimal post-operative complications.

Stereotactic MRI-guided laser interstitial thermal therapy for extratemporal lobe epilepsy.

OBJECTIVE: Magnetic resonance imaging (MRI)-guided laser interstitial thermal therapy (MRg-LITT) is an alternative to open epilepsy surgery. We assess safety and effectiveness of MRg-LITT for extratemporal lobe epilepsy (ETLE) in patients who are considered less favorable for open resection. METHODS: We retrospectively reviewed sequential cases of patients with focal ETLE who underwent MRg-LITT between 2012 and 2019. Epileptogenic zones were determined from standard clinical and imaging data ± stereoelectroencephalography (SEEG). Standard stereotactic techniques, MRI thermometry, and a commercial laser thermal therapy system were used for ablations. Anatomic MRI was used to calculate ablation volumes. Clinical outcomes were determined longitudinally. RESULTS: Thirty-five patients with mean epilepsy duration of 21.3 ± 12.2 years underwent MRg-LITT for focal ETLE at a mean age 36.4 ± 12.7 years. A mean 2.59 ± 1.45 trajectories per patient were used to obtain ablation volumes of 8.8 ± 7.5 cm3 . Mean follow-up was 27.3 ± 19.5 months. Of 32 patients with >12 months of follow-up, 17 (53%) achieved good outcomes (Engel class I + II) of whom 14 (44%) were Engel class I. Subgroup analysis revealed better outcomes for patients with lesional ETLE than for those who were nonlesional, multifocal, or who had failed prior interventions (P = .02). Of 13 patients showing favorable seizure-onset patterns (localized low voltage fast activity or rhythmic spiking on SEEG) prior to ablation, 9 (69%) achieved good outcomes, whereas only 3 of 11 (27%) who show other slower onset patterns achieved good outcomes. Minor adverse events included six patients with transient sensorimotor neurologic deficits and four patients with asymptomatic hemorrhages along the fiber tract. Major adverse events included one patient with a brain abscess that required stereotactic drainage and one patient with persistent hypothalamic obesity. Three deaths-two seizure-associated and one suicide-were unrelated to surgical procedures. SIGNIFICANCE: MRI-guided laser interstitial thermal therapy (or MRg-LITT) was well-tolerated and yielded good outcomes in a heterogeneous group of ETLE patients. Lesional epilepsy and favorable seizure-onset patterns on SEEG predicted higher likelihoods of success.

Novel Use of Stimulating Fence-Post Technique for Functional Mapping of Subcortical White Matter During Tumor Resection: A Technical Case Series.

BACKGROUND: Maximal safe resection remains a key principle in infiltrating glioma management. Stimulation mapping is a key adjunct for minimizing functional morbidity while "fence-post" procedures use catheters or dye to mark the tumor border at the start of the procedure prior to brain shift. OBJECTIVE: To report a novel technique using stereotactically placed electrodes to guide tumor resection near critical descending subcortical fibers. METHODS: Navigated electrodes were placed prior to tumor resection along the deep margin bordering presumed eloquent tracts. Stimulation was administered through these depth electrodes for subcortical motor and language mapping. RESULTS: Twelve patients were included in this preliminary technical report. Seven patients (7/12, 58%) were in asleep cases, while the other 5 cases (5/12, 42%) were performed awake. Mapping of motor fibers was performed in 8 cases, and language mapping was done in 1 case. In 3 cases, both motor and language mapping were performed using the same depth electrode spanning corticospinal tract and the arcuate fasciculus. CONCLUSION: Stereotactic depth electrode placement coupled with stimulation mapping of white matter tracts can be used concomitantly to demarcate the border between deep tumor margins and eloquent brain, thus helping to maximize extent of resection while minimizing functional morbidity.

Elucidating Pro-Inflammatory Cytokine Responses after Traumatic Brain Injury in a Human Stem Cell Model.

Cytokine mediated inflammation likely plays an important role in secondary pathology after traumatic brain injury (TBI). The aim of this study was to elucidate secondary cytokine responses in an in vitro enriched (>80%) human stem cell-derived neuronal model. We exposed neuronal cultures to pre-determined and clinically relevant pathophysiological levels of tumor necrosis factor-α (TNF), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß), shown to be present in the inflammatory aftermath of TBI. Data from this reductionist human model were then compared with our in vivo data. Human embryonic stem cell (hESC)-derived neurons were exposed to recombinant TNF (1-10,000 pg/mL), IL-1ß (1-10,000 pg/mL), and IL-6 (0.1-1000 ng/mL). After 1, 24, and 72 h, culture supernatant was sampled and analyzed using a human cytokine/chemokine 42-plex Milliplex kit on the Luminex platform. The culture secretome revealed both a dose- and/or time-dependent release of cytokines. The IL-6 and TNF exposure each resulted in significantly increased levels of >10 cytokines over time, while IL-1ß increased the level of C-X-C motif chemokine 10 (CXCL10/IP10) alone. Importantly, these patterns are consistent with our in vivo (human) TBI data, thus validating our human stem cell-derived neuronal platform as a clinically useful reductionist model. Our data cumulatively suggest that IL-6 and TNF have direct actions, while the action of IL-1ß on human neurons likely occurs indirectly through inflammatory cells. The hESC-derived neurons provide a valuable platform to model cytokine mediated inflammation and can provide important insights into the mechanisms of neuroinflammation after TBI.

Neurosurgical management in lateral meningocele syndrome: case report.

Lateral meningocele syndrome (LMS) is a rare genetic connective tissue disorder. It is associated with morphological changes similar to those of other connective tissue disorders, with the unique distinction of multiple, often bilateral and large, lateral meningoceles herniating through the spinal foramina. In some cases, these lateral meningoceles can cause pain and discomfort due to their presence within retroperitoneal tissues or cause direct compression of the spinal nerve root exiting the foramen; in some cases compression may also involve motor weakness. The presence of lateral meningoceles imposes unique challenges related to CSF flow dynamics, especially with concurrent Chiari malformation, which also occurs with increased frequency in individuals with LMS. The authors present the case of a 6-month-old female with LMS with multiple lateral meningoceles throughout the thoracic and lumbar spine. The infant experienced a focal neurological abnormality due to enlargement of her lateral meningoceles following decompression of a symptomatic Chiari malformation and endoscopic third ventriculostomy. The finding was reversed through implantation of a ventriculoperitoneal shunt, which reduced the burden of CSF upon the lateral meningoceles. Such a case compels consideration that CSF flow dynamics in addition to altered connective tissue play a role in the presence of lateral meningoceles in patients within this and similar patient populations.

Classification of middle fossa floor dehiscence syndromes.

OBJECT: Middle fossa floor dehiscence (MFFD) can present as multiple syndromes depending on dehiscence location, tissue herniation, and dural integrity. The authors propose a classification system for MFFD with the potential to guide clinical decision making. METHODS: A retrospective analysis of the electronic medical records (years 1995-2012) of patients who had undergone temporal craniotomy for the surgical repair of an MFFD syndrome at a single institution was undertaken. Reviewed data included demographic, operative, presentation, and outcome details. Middle fossa floor dehiscence was classified as follows: Class A, bony dehiscence without herniation of the brain and/or meninges; Class B, herniation of the brain and/or meninges through the middle fossa floor without CSF leakage; Class C, dehiscence with CSF leakage without meningitis; or Class D, dehiscence with meningitis. RESULTS: Fifty-one patients, 22 males and 29 females, were included in the analysis. The mean age was 48.7 ± 15.5 years, mean body mass index was 32.65 ± 6.86 kg/m(2), and mean symptom duration was 33 ± 42 months. Seven patients underwent repeat surgery for symptomatic recurrence; therefore, there were 58 surgical encounters. Repair included bony reconstruction with hydroxyapatite with or without resection of encephaloceles and/or repair of a dural defect. According to the MFFD classification system described, 15, 8, 27, and 8 cases were categorized as Class A, B, C, and D, respectively. The prevalence of hearing loss was 87%, 63%, and 70% in Classes A, B, and C, respectively. Vestibular symptoms were more prevalent in Class A. Seven patients reported persistent symptoms at the last follow-up. Transient complications were similar in each classification (13%-25%), and a single permanent complication related to anesthesia was observed. There were no mortalities or severe neurological morbidities in the series. CONCLUSIONS: Middle fossa floor dehiscence has a spectrum of clinical presentations. A classification system may help to clarify the diagnosis and guide therapy. Surgery, the mainstay of treatment, is safe and well tolerated.

Provider-verified HPV vaccine coverage among a national sample of Hispanic adolescent females.

BACKGROUND: Hispanic females have the highest cervical cancer incidence rate of any racial or ethnic group in the United States, yet relatively little research has examined human papillomavirus (HPV) vaccination among this fast-growing population. We examined HPV vaccination among a national sample of Hispanic adolescent females. METHODS: We analyzed provider-verified vaccination data from the 2010-2011 National Immunization Survey-Teen for Hispanic females ages 13 to 17 years (n = 2,786). We used weighted logistic regression to identify correlates of HPV vaccine initiation (receipt of one or more doses), completion (receipt of three doses), and follow-through (receipt of three doses among those who initiated the series). RESULTS: HPV vaccine initiation was 60.9%, completion was 36.0%, and follow-through was 59.1%. Initiation and completion were more common among older daughters and those whose parents had received a provider recommendation to vaccinate (all P < 0.05). Completion was less common among daughters who had moved from their birth state (P < 0.05). All vaccination outcomes were less common among daughters without health insurance (all P < 0.05). Vaccination did not differ by parents' preferred language (all P > 0.05), although intent to vaccinate was higher among Spanish-speaking parents (P < 0.01). Spanish-speaking parents were more likely to indicate lack of provider recommendation (20.2% vs. 5.3%) and cost (10.9% vs. 1.8%) as main reasons for not intending to vaccinate (both P < 0.05). CONCLUSIONS: Many Hispanic females have not received HPV vaccine. Several factors, including provider recommendation and health insurance, are key correlates of vaccination. IMPACT: HPV vaccination programs targeting Hispanics are needed and should consider how potential barriers to vaccination may differ by preferred language.

Multifunctional roles for serum protein fetuin-a in inhibition of human vascular smooth muscle cell calcification.

Vascular calcification predicts an increased risk for cardiovascular events/mortality in atherosclerosis, diabetes, and ESRD. Serum concentrations of alpha(2)-Heremens-Schmid glycoprotein, commonly referred to as fetuin-A, are reduced in ESRD, a condition associated with an elevated circulating calcium x phosphate product. Mice that lack fetuin-A exhibit extensive soft tissue calcification, which is accelerated on a mineral-rich diet, suggesting that fetuin-A acts to inhibit calcification systemically. Western blot and immunohistochemistry demonstrated that serum-derived fetuin-A co-localized with calcified human vascular smooth muscle cells (VSMC) in vitro and in calcified arteries in vivo. Fetuin-A inhibited in vitro VSMC calcification, induced by elevated concentrations of extracellular mineral ions, in a concentration-dependent manner. This was achieved in part through inhibition of apoptosis and caspase cleavage. Confocal microscopy and electron microscopy-immunogold demonstrated that fetuin-A was internalized by VSMC and concentrated in intracellular vesicles. Subsequently, fetuin-A was secreted via vesicle release from apoptotic and viable VSMC. Vesicles have previously been identified as the nidus for mineral nucleation. The presence of fetuin-A in vesicles abrogated their ability to nucleate basic calcium phosphate. In addition, fetuin-A enhanced phagocytosis of vesicles by VSMC. These observations provide evidence that the uptake of the serum protein fetuin-A by VSMC is a key event in the inhibition of vesicle-mediated VSMC calcification. Strategies aimed at maintaining normal circulating levels of fetuin-A may prove beneficial in patients with ESRD.

Tumor suppressor activity and epigenetic inactivation of hepatocyte growth factor activator inhibitor type 2/SPINT2 in papillary and clear cell renal cell carcinoma.

Following treatment with a demethylating agent, 5 of 11 renal cell carcinoma (RCC) cell lines showed increased expression of hepatocyte growth factor (HGF) activator inhibitor type 2 (HAI-2/SPINT2/Bikunin), a Kunitz-type protease inhibitor that regulates HGF activity. As activating mutations in the MET proto-oncogene (the HGF receptor) cause familial RCC, we investigated whether HAI-2/SPINT2 might act as a RCC tumor suppressor gene. We found that transcriptional silencing of HAI-2 in RCC cell lines was associated with promoter region methylation and HAI-2/SPINT2 protein expression was down-regulated in 30% of sporadic RCC. Furthermore, methylation-specific PCR analysis revealed promoter region methylation in 30% (19 of 64) of clear cell RCC and 40% (15 of 38) of papillary RCC, whereas mutation analysis (in 39 RCC cell lines and primary tumors) revealed a missense substitution (P111S) in one RCC cell line. Restoration of HAI-2/SPINT2 expression in a RCC cell line reduced in vitro colony formation, but the P111S mutant had no significant effect. Increased cell motility associated with HAI-2/SPINT2 inactivation was abrogated by treatment with extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and phospholipase C-gamma inhibitors, but not by an inhibitor of atypical protein kinase C. These findings are consistent with frequent epigenetic inactivation of HAI-2/SPINT2, causing loss of RCC tumor suppressor activity and implicate abnormalities of the MET pathway in clear cell and papillary sporadic RCC. This information provides opportunities to develop novel targeted approaches to the treatment of RCC.