Riluzole in Spinal Cord Injury Study (RISCIS)-Pharmacokinetic (PK) Sub-Study: An Analysis of Pharmacokinetics, Pharmacodynamics, and Impact on Axonal Degradation of Riluzole in Patients With Traumatic Cervical Spinal Cord Injury Enrolled in the RISCIS Phase III Randomized Controlled Trial.

To date, no drug therapy has shown significant efficacy in improving functional outcomes in patients with acute spinal cord injury (SCI). Riluzole is an approved benzothiazole sodium channel blocker to attenuate neurodegeneration in amyotrophic lateral sclerosis (ALS) and is of interest for neuroprotection in SCI. In a Phase I clinical trial (ClinicalTrials.gov Identifier: NCT00876889), riluzole was well tolerated with a 2-week treatment at the dose level approved for ALS and exhibited potential efficacy in patients with SCI. The acute and progressive nature of traumatic SCI and the complexity of secondary injury processes alter the pharmacokinetics (PK) of therapeutics. In the PK sub-study of the multi-center, randomized, placebo-controlled, double-blinded Riluzole in Spinal Cord Injury Study (RISCIS) Phase II/III trial (ClinicalTrials.gov Identifier: NCT01597518), a total of 32 SCI patients were enrolled, and most of our patients were middle-age Caucasian males with head and neck injuries. We studied the PK and pharmacodynamics (PD) of riluzole on motor recovery, measured by International Standards for Neurological Classification of SCI (ISNCSCI) Motor Score at injury and at 3-month and 6-month follow-ups, along with levels of the axonal injury biomarker phosphorylated neurofilament heavy chain (pNF-H), during the 2-week treatment. PK modeling, PK/PD correlations were developed to identify the potential effective exposure of riluzole for intended PD outcomes. The longitudinal impacts of SCI on the PK of riluzole are characterized. A time-varying population PK model of riluzole is established, incorporating time-varying clearance and volume of distribution from combined data of Phase I and Phase II/III trials. With the developed model, a rational, optimal dosing scheme can be designed with time-dependent modification to preserve the required therapeutic exposure of riluzole. The PD of riluzole and the relationship between PK and neurological outcomes of the treatment were established. The time course of efficacy in total motor score improvement (ΔTMS) and pNF-H were monitored. A three-dimensional (3D) PK/PD correlation was established for ΔTMS at 6 months with overall riluzole exposure area under the curve for Day 0-Day14 (AUCD0-D14) and baseline TMS for individual patients. Patients with baseline TMS between 1 and 36 benefited from the optimal exposure range of 16-48 mg*h/mL. The PD models of pNF-H revealed the riluzole efficacy, as treated subjects exhibited a diminished increase in progression of pNF-H, indicative of reduced axonal breakdown. The independent parameter of area between effective curves (ABEC) between the time profiles of pNF-H in placebo and treatment groups was statistically identified as a significant predictor for the treatment effect on the biomarker. A mechanistic clinical outcomes (CO)/PD (pNF-H) model was established, and the proposed structure demonstrated the feasibility of PK/PD/CO correlation model. No appreciable hepatic toxicity was observed with the current riluzole treatment regimen. The development of effective treatment for SCI is challenging. However, the future model-informed and PK-guided drug development and regimen modification can be rationally executed with the optimal dosing regimen design based on the developed 3D PK/PD model. The PK/PD/CO model can serve as a rational guide for future drug development, PKPD model refinement, and extension to other studies in SCI settings.

A new treatment for cervical vertigo with botulinum toxin.

A new and unique treatment for cervical vertigo with botulinum toxin is presented for a woman who sustained neck trauma from being hit by a wave. A diagnosis of cervical vertigo and cervical dystonia was confirmed by history, physical exam, dystonia on EMG exam, and a negative test for benign paroxysmal positional vertigo. She experienced consistent resolution of her vertigo symptoms and pain after each treatment for a total of 5 treatments with botulinum toxin to the upper cervical muscles.This report appears to be the first to demonstrate the missing link between vertigo and cervical dystonia with pain. Chemodenervation was effective in treating cervical vertigo and is likely to have altered the cervical proprioceptive input by relaxing the overactive muscles and/or by decompression of cervical nerves.

Multiple cranial nerve injuries and neck abscesses caused by a transorally penetrating organic stick.

Foreign bodies cause a remarkable number of otolaryngological emergency visits and occasionally result in life-threatening conditions and later-emerging complications. Patient recovery depends on the detection and proper extraction of all foreign materials. Despite various obtainable diagnostic tools, adequate anamnesis forms the basis of clinical reasoning and should direct later examinations and radiological imaging. This case report describes a challenging patient with a unique trauma mechanism: many pieces of a fragmented organic foreign body emerged within 1 year of the initial injury, leading to repeated operations, a long period in an intensive care unit and a long-term swallowing and speech dysfunction.

Subcutaneous emphysema to the head and neck: an unlikely traumatic origin.

Subcutaneous emphysema to the neck represents a rare entity mainly derived from iatrogenic and traumatic origin. We report a case of a subcutaneous emphysema resulted from an intraoral injury aiming to emphasise the significance of precise medical history to identify an unlikely mechanism. A 40-year-old female patient was presented with subcutaneous emphysema extending from the region underneath the left eye up to the submandibular area of the neck. The patient complained of painful, swollen neck. The patient mentioned that the symptoms began after an intraoral injury accidentally caused by the use of a high-pressure water jet device meant for car wash. The patient was managed conservatively and was discharged after 2 days. This case highlights the urgency for clinical suspicion for unlikely mechanisms. Moreover, the manufacturer companies should alert and give official warning for the contingency of injury due to incorrect or careless usage.

Fatores de risco para lesões cervicais e câncer cervical em Mulheres com diagnóstico citológico de células escamosas Atípicas, maputo-moçambique, 2013 - 2015 / Risk factors for cervical lesions and cervical cancer in women with cytological diagnosis of atypical squamous cells, maputo-mozambique, 2013 - 2015

Introdução: O diagnóstico e o rastreamento das lesões cervicais são de suma importância. O método padrão de rastreamento do câncer do colo do útero e de suas lesões precursoras é o exame citológico pelo método de Papanicolaou. Objetivos: Estimar a prevalência das lesões cervicais de baixo e alto grau e câncer cervical em mulheres com diagnóstico citológico de células escamosas atípicas, verificar a influência dos agentes etiológicos de doenças com a presença das lesões cervicais e câncer cervical. Método: estudo transversal com abordagem quantitativa, coleta de dados retrospectiva, realizado no Departamento de ginecologia e obstetrícia, e no serviço de anatomia patológica do Hospital Central de Maputo, em Moçambique. Foram estudados 358 prontuários de Janeiro de 2013 a Dezembro de 2015 de mulheres com diagnóstico citológico de células escamosas atípicas. Considerouse como estatisticamente significante as variáveis p<0,05, calculou se a frequência de diagnósticos com seus respectivos intervalos de confiança (IC95%). A presença das lesões e o grau de associação entre as variáveis dependentes e independentes foi verificada através do cálculo do coeficiente de correlação de Pearson e razão de prevalência (RP). Resultados: a média da idade foi de 38,1 anos, mediana 36,6 e o desvio padrão de 12,3. A idade variou entre 17 a 71 anos. A prevalência das lesões cervicais foi de 153 casos (63%), sendo lesão de baixo grau (NIC I) 50 (32,7%) e lesão de alto grau /carcinoma invasor (NIC 2+) 103 (67,3%). Os fatores de risco associados às lesões cervicais e câncer cervical foram: idade (40-49) (P=0,001), profissão (doméstica) (P=0,016), Paridade (+de 5) (P=0,001), menopausa (P=0,001), HPV (P=0,001), e Tricomonas vaginalis (P=0,001).Conclusão: A prevalência das lesões cervicais de alto grau em mulheres com diagnóstico citológico de células escamosas atípicas foi alta. Os fatores de risco associados às lesões cervicais mais severas em pacientes com citologia de células escamosas atípicas foram: idade paridade, profissão, menopausa. Os agentes etiológicos de doenças que influenciaram no desenvolvimento das lesões cervicais e câncer cervical foram o HPV e Tricomonas vaginalis.

Traumatic bilateral carotid artery dissection following severe blunt trauma: a case report on the difficulties in diagnosis and therapy of an often overlooked life-threatening injury.

BACKGROUND: Traumatic carotid artery dissections are very rare, often overlooked and life-threatening injuries. Diagnosis and treatment are difficult especially in multiple injured patients. CASE PRESENTATION: We report on a 28-year-old female major trauma patient (injury severity score, ISS 50) who was involved in a motor vehicle accident. She was primarily transferred to a level II trauma center. After initial assessment and operative management, an anisocoria was diagnosed on the intensive care unit. Subsequent CT angiography and extracranial duplex sonography revealed a bilateral internal carotid artery dissection. The patient was transferred to our level I trauma center where conservative treatment with high-dose heparin therapy was started at day two after trauma. Outcome after 6 months was very good. CONCLUSION: Besides presenting the case and outcome of this patient, the article discusses the diagnostic and therapeutic management of this extremely rare and often overlooked dangerous injury. To avoid overlooking carotid artery dissections, CT angiography of the neck region should be generously included into the initial multislice CT whole-body scan, when the injury results from an according trauma. For the best outcome, sites of hemorrhage should be abolished quickly and the anticoagulative therapy should be initiated as soon as possible. Interdisciplinary treatment of trauma surgeons and neurologists is crucial.

Infarto cerebeloso debido a disección de la arteria vertebral extracraneal causada por rotación brusca delcuello: reporte de caso / Cerebellar infarct due to extracranial vertebral artery dissection caused by sudden neck rotation: a case report

Introducción: La disección de las arterias carótidas y vertebrales representa una causa rara de ictus, y su mayor incidencia se reporta en los pacientes jóvenes y en la edad media de la vida. La presentación de este caso tiene como objetivo mostrar la variedad de manifestaciones clínicas de la disección de la arteria vertebral y algunos de los problemas actuales en su manejo.Caso clínico: Paciente masculino de 42 años que luego de un giro brusco de la cabeza comenzó con un cuadro de mareos que mejoraban con el decúbito y se exacerbaban con los cambios de posición. En la exploración neurológica se encontraron signos de focalización neurológica como ataxia de la marcha, dismetría, disdiadococinesia, hipotonía muscular derecha, y paresia del músculo recto lateral derecho por afectación del VI nervio craneal. En las imágenes de resonancia magnética se encontró un infarto en el hemisferio cerebeloso derecho y la angioTAC multicorte de cráneo permitió observar los signos de la disección de la arteria vertebral derecha. Se decidió el ingreso en la sala de Neurología con el diagnóstico de ictus isquémico del territorio posterior de causa inhabitual. Se comenzótratamiento con aspirina (125 mg/día). A los 10 días de evolución comenzó con mejoría importante y paulatinamente ocurrió la desaparición de los síntomas focales neurológicos.Conclusiones: Este caso de disección arterial reafirma la necesidad de considerar esta entidad como causa de ictus isquémico en el adulto joven. La atribución de los síntomas a procesos menos graves y la variabilidad de los síntomas enseñan que al interrogar yexaminar a un paciente se requiere de gran pericia y de la correlación neuroanatómica y cronológica de los hallazgos. Asimismo, es fundamental un diagnóstico rápido y el inicio precoz de una terapia con el potencial de cambiar el curso de esta entidad(AU)

Introduction: Carotid and vertebral arteries dissection represents a rare cause of stroke, and it´s reported mainly in young and middle age patients. This case shows the variable resentation of vertebral artery dissection and some current management problems.Clinical case: 42-year-old male patient who began in the morning after a sudden head rotation with dizziness that improved with decubitus and were exacerbated with the changes of position. Neurological examination revealed focal signs as ataxic gait, dysmetria, dysdiadochokinesis, right muscle hypotonia, and paresis of right abducens muscle due cranial nerve VI lesion. Magnetic resonance imagesshowed an infarct in right cerebellar hemisphere and angioCT scan showed right vertebral artery dissection. It was decided hospitalization in neurology service with diagnosis of ischemic stroke of posterior territory. Then the patient received treatment with aspirin (125 mg/day).After 10 days of evolution, he began with improvement of the neurological focal symptoms, and later with disappearance of neurological signs.Conclusions: This case reaffirms the need to consider this entity as cause of ischemic stroke in young adults. The attribution of symptoms to minor conditions and symptoms variability teach the value of capacity for history collection and examination, anatomic correlation and chronologic approach. Also, is fundamental a rapid diagnosis and the early beginning of therapy, that can potentially change the evolutionof this entity(AU)

Treatment of cervicogenic headache with cervical epidural steroid injection.

Cervicogenic headache (CGH) is defined as referred pain from various cervical structures innervated by the upper three cervical spinal nerves. Such structures are potential pain generators, and include the atlanto-occipital joint, atlantoaxial joint, C2-3 zygapophysial joint, C2-3 intervertebral disc, cervical myofascial trigger points, as well as the cervical spinal nerves. Various interventional techniques, including cervical epidural steroid injection (CESI), have been proposed to treat this disorder. And while steroids administered by cervical epidural injection have been used in clinical practice to provide anti-inflammatory and analgesic effects that may alleviate pain in patients with CGH, the use of CESI in the diagnosis and treatment of CGH remains controversial. This article describes the neuroanatomy, neurophysiology, and classification of CGH as well as a review of the available literature describing CESI as treatment for this debilitating condition.

Impact of intravenous acetaminophen therapy on the necessity of cervical spine imaging in patients with cervical spine trauma.

OBJECTIVE: We evaluated a new hypothesis of acetaminophen therapy to reduce the necessity of imaging in patients with probable traumatic cervical spine injury. METHODS: Patients with acute blunt trauma to the neck and just posterior midline cervical tenderness received acetaminophen (15 mg/kg) intravenously after cervical spine immobilization. Then, all the patients underwent plain radiography and computerized tomography of the cervical spine. The outcome measure was the presence of traumatic cervical spine injury. Sixty minutes after acetaminophen infusion, posterior midline cervical tenderness was reassessed. RESULTS: Of 1 309 patients, 41 had traumatic cervical spine injuries based on imaging. Sixty minutes after infusion, posterior midline cervical tenderness was eliminated in 1 041 patients, none of whom had abnormal imaging. CONCLUSION: Patients with cervical spine trauma do not need imaging if posterior midline cervical tenderness is eliminated after acetaminophen infusion. This analgesia could be considered as a diagnostic and therapeutic intervention.

Riluzole effects on behavioral sensitivity and the development of axonal damage and spinal modifications that occur after painful nerve root compression.

OBJECT: Cervical radiculopathy is often attributed to cervical nerve root injury, which induces extensive degeneration and reduced axonal flow in primary afferents. Riluzole inhibits neuro-excitotoxicity in animal models of neural injury. The authors undertook this study to evaluate the antinociceptive and neuroprotective properties of riluzole in a rat model of painful nerve root compression. METHODS: A single dose of riluzole (3 mg/kg) was administered intraperitoneally at Day 1 after a painful nerve root injury. Mechanical allodynia and thermal hyperalgesia were evaluated for 7 days after injury. At Day 7, the spinal cord at the C-7 level and the adjacent nerve roots were harvested from a subgroup of rats for immunohistochemical evaluation. Nerve roots were labeled for NF200, CGRP, and IB4 to assess the morphology of myelinated, peptidergic, and nonpeptidergic axons, respectively. Spinal cord sections were labeled for the neuropeptide CGRP and the glutamate transporter GLT-1 to evaluate their expression in the dorsal horn. In a separate group of rats, electrophysiological recordings were made in the dorsal horn. Evoked action potentials were identified by recording extracellular potentials while applying mechanical stimuli to the forepaw. RESULTS: Even though riluzole was administered after the onset of behavioral sensitivity at Day 1, its administration resulted in immediate resolution of mechanical allodynia and thermal hyperalgesia (p < 0.045), and these effects were maintained for the study duration. At Day 7, axons labeled for NF200, CGRP, and IB4 in the compressed roots of animals that received riluzole treatment exhibited fewer axonal swellings than those from untreated animals. Riluzole also mitigated changes in the spinal distribution of CGRP and GLT-1 expression that is induced by a painful root compression, returning the spinal expression of both to sham levels. Riluzole also reduced neuronal excitability in the dorsal horn that normally develops by Day 7. The frequency of neuronal firing significantly increased (p < 0.045) after painful root compression, but riluzole treatment maintained neuronal firing at sham levels. CONCLUSIONS: These findings suggest that early administration of riluzole is sufficient to mitigate nerve root-mediated pain by preventing development of neuronal dysfunction in the nerve root and the spinal cord.

Vertebral artery dissection after neck extension in an adult patient with Klippel-Feil syndrome.

The association between Klippel-Feil syndrome and vertebral artery dissection is quite rare. We report an adult patient with vertebral artery dissection and Klippel-Feil syndrome, to our knowledge only the third reported case of its kind. A 45-year-old woman with a known history of Klippel-Feil syndrome presented with occipital head and neck pain following forced neck extension. Diagnostic cerebral angiography revealed a high grade vertebral artery stenosis, consistent with vertebral artery dissection. Following 6 months of medical management, a repeat diagnostic angiogram revealed complete healing of the vessel. While cervical fusion, as seen in Klippel-Feil syndrome, has previously been shown to cause neurologic injury secondary to hypermobility, the association with vertebral artery dissection is incredibly rare. We hypothesize that this hypermobility places abnormal shear force on the vessel, causing intimal injury and dissection. Patients with seemingly spontaneous vertebral artery dissection may benefit from cervical spine radiography, and this predisposition to cerebrovascular injury strongly suggests further evaluation of vascular injury following trauma in patients with Klippel-Feil syndrome or other cervical fusion as clinically warranted.

[Medical honey in the treatment of wound-healing disorders in the head and neck area]. / Erste Erfahrungen mit medizinischem Honig in der Wundbehandlung im Kopf-Hals-Bereich.

BACKGROUND: Already in ancient times honey was used as a drug and for the treatment of wounds. In recent years the different effects of honey on wound-healing processes have been reexamined. Based on this, the antibacterial and fungicidal qualities of honey could be confirmed. PATIENTS AND METHODS: Between January 2009 and July 2011 medical honey was used on 36 patients suffering from different wound-healing disorders in the head and neck area after unsuccessful conventional treatment. The healing process was registered by microbiological investigations, measurements of the wound edges and adequate photo documentation. RESULTS: Medical honey can be used without problems or detectable side effects on problematic wounds of the head and neck area. Constant treatment leads to fast wound lavation, granulation, reduction of putrid smells and a decrease in inflammation. CONCLUSIONS: In the treatment of poorly healing and infected wounds within the head and neck area, medical honey can be used successfully without problems as an effective alternative to conventional treatment options.

[Cervico-facial traumatic injuries at the Donka national hospital of the teaching hospital of Conakry]. / Les Plaies Traumatiques Cervico-Faciales A L'Hopital National Donka Du CHU De Conakry.

The Cervico-Facial Traumatic Injuries (CFTI) can entrain complications and serious aesthetic and functional sequella. The objectives of this study were to determine the frequency of CFTI, to describe the clinical forms and to evaluate the treatment. It was a prospective study conducted from February to July 2010 in the National Donka hospital of the Teaching Hospital of Conakry. The study concerned 265 patients, who benefited a treatment and reevaluated. The young adults aged between 21-30 years were the most affected (38.49%). 74.34 % were men and 25.66 % were females with a sex ratio of 2.9. Road accident was the etiology of injuries in 70.57% of cases. Clinically, the lesions were dominated by the wounds type II (49.05 %) followed by the wounds type I (48.30 %) and 2,65 % of wounds was type III. The treatment was medical and surgical. Evolution was considered favorable in 82.13 % of cases and disfavorable in 17.85 % of cases.

Pneumomediastinum and subcutaneous emphysema due to blunt neck injury: a case report and review of the literature.

Minor blunt neck injury from childhood trauma is a relatively common condition which can be potentially life-threatening in only rare circumstances. Pneumomediastinum may develop in up to 10% patients who have sustained blunt cervical or thoracic trauma and may be a significant cause of morbidity and mortality in affected individuals because of the associated damage to the oesophagus, larynx or trachea. Management of this condition varies from conservative approach with close observation and antibiotherapy to surgical interventions, depending on the extent and severity of aerodigestive injuries. We present a paediatric blunt neck trauma accompanied by subcutaneous emphysema and pneumomediastinum secondary to a bicycle accident (neck striking the handlebar). Its radiologic appearance, clinical presentation, and the options for initial management in the emergency department (ED) are reviewed.

Evaluation of LHP® (1% hydrogen peroxide) cream versus petrolatum and untreated controls in open wounds in healthy horses: a randomized, blinded control study.

BACKGROUND: Treatment and protection of wounds in horses can be challenging; protecting bandages may be difficult to apply on the proximal extremities and the body. Unprotected wounds carry an increased risk of bacterial contamination and subsequent infection which can lead to delayed wound healing. Topical treatment with antimicrobials is one possibility to prevent bacterial colonization or infection, but the frequent use of antimicrobials ultimately leads to development of bacterial resistance which is an increasing concern in both human and veterinary medicine. METHODS: Standardized wounds were created in 10 Standardbred mares. Three wounds were made in each horse. Two wounds were randomly treated with LHP® or petrolatum and the third wound served as untreated control. All wounds were assessed daily until complete epithelization. Protocol data were recorded on day 2, 6, 11, 16, 21 and 28. Data included clinical scores for inflammation and healing, photoplanimetry for calculating wound areas and swab cytology to assess bacterial colonization and inflammation. Bacterial cultures were obtained on day 2, 6 and 16. RESULTS: Mean time to complete healing for LHP® treated wounds was 32 days (95%CI=26.9-37.7). Mean time to complete healing for petrolatum and untreated control wounds were 41.6 days (95%CI=36.2-47.0) and 44.0 days (95%CI=38.6-49.4) respectively. Wound healing occurred significantly faster in LHP® wounds compared to both petrolatum (p=0.0004) and untreated controls (p<0.0001). There was no significant difference in time for healing between petrolatum and untreated controls. Total scores for bacteria and neutrophils were significantly (p<0.0001) lower for LHP® treated wounds compared to petrolatum from day 16 and onwards. Staphylococcus aureus and Streptococcus zooepidemicus were only found in cultures from petrolatum treated wounds and untreated controls. CONCLUSIONS: Treatment with LHP® reduced bacterial colonization and was associated with earlier complete wound healing. LHP® cream appears to be safe and effective for topical wound treatment or wound protection.

[Traumatic vertebral artery dissection in an 8 year old boy]. / Traumatische Vertebralisdissektion bei einem 8-Jährigen.

Dissections of extracranial brain supplying arteries are a common cause of ischemic strokes in young patients. Accidents are often accountable for that. We report the case of an 8 year old boy with traumatic vertebral dissection after he was bumped while playing football. He developed an ischemia on both sides of the thalamus which was caused by a bilateral system of the vertebral artery. He showed motor eye and progressive neuropsychological deficits. The CT and MRI scan confirmed the diagnosis. The symptoms ameliorated under anticoagulation treatment with intravenous heparin. At the end of the hospital stay, neuropsychological deficits persisted. Doppler ultrasound showed recanalization of the vertebral artery. Further treatment consisted of anticoagulation with marcumar for 6 months.

[Effect of ozone on antibiotic sensitivity of microorganisms]. / Vliianie ozona ha chuvstvitel'nost' mikroorganizmov k antibiotikam.

Ozone therapy of wounds of the face and neck notably increased the sensitivity of microorganisms to antibiotics in 79% cases.

Necrotizing soft tissue infections of the head and neck: case reports and literature review.

A small but nevertheless important part of a surgeon's experience comprises necrotizing soft tissue infections of the head and neck. The purpose of this report is to heighten awareness of necrotizing soft tissue infections in any patient with an infection of the head and neck. The article also outlines an appropriate management strategy for use in the treatment of patients with this potentially fatal condition. Prompt diagnosis and early radical surgical debridement are significant factors in avoiding a fatal outcome in these patients. This article reviews the literature on necrotizing soft tissue infections of the head and neck and presents cases from our recent experience.