[The hypolossal-facial anastomosis in man. A model for studying peripheral and central nervous system plasticity]. / L'anastomose hypoglosso-faciale chez l'homme: un modèle d'etude de la plasticité du système nerveux périphérique et central.

Hypoglossal-facial anastomosis (HFA) is a cross-over between the proximal stump of the hypoglossal nerve (XII) and the distal one of the facial nerve (VII). The hypoglossal axons regrow within the sheaths of facial fibres, allowing the progressive reinnervation of the facial muscles. This model is interesting to study some mechanisms of plasticity of the nervous system for several reasons: 1) It is a quite simple and reproducible model of pathophysiological state. It allows the study of 2) the modifications of the nervous system induced by the HFA, both upwards and downwards to the lesion and 3) the modifications of reflex activities involving intrapontine connections such as the blink reflex. The electrophysiological features of the trigemino-facial (TF) and trigemino-hypoglossal (TG) connections demonstrated that a central reorganisation of the blink reflex (BR) was induced by HFA: the afferent volleys of the TF and TH reflexes elicited by cutaneous and mucosal trigeminal afferents respectively have been shown to project onto common interneurones located within the trigeminal principal sensory nucleus. A long-term prospective study showed: 1) a reinnervation of the facial muscles by the hypoglossal axons is a necessary perequisite for the central reorganisation of BR, 2) a hyperinnervation of the facial muscles by the hypoglossal axons, 3) a transient and regressive cross-innervation of paralyzed face by the healthy contralateral facial nerve.

Hypoglossal-facial nerve anastomosis: dynamic insight into the cross-innervation phenomenon.

The authors investigated the evolution of the dynamic features of the cross-innervation process in patients with complete facial palsy due to facial nerve transection during surgery for acoustic neuroma removal followed by a hypoglossal-facial nerve anastomosis (HFA). Clinical and electrophysiologic investigations were carried out before and over a 3-year period after HFA. Cross-innervation had started by the 10th day, progressed to the seventh to eighth month, then decreased and finally disappeared by the 12th month after HFA. Ipsilateral reinnervation was observed by the fourth month, progressed to the 12th to 18th month, and remained stable for the remainder of the follow-up period.

[Comparative evaluation of speech disorders and verbal and non verbal communication within two groups of patients: patients with facial paralysis (FP) and those who had undergone hypoglosso-facial anastomosis (HFA)]. / Evaluation comparative des troubles articulatoires et de la communication verbale et non-verbale entre patients porteurs d'une paralysie faciale (PF) et ceux opérés ayant subi une anastomose hypoglossso-faciale (AHF).

INTRODUCTION: Speech disorders were often allotted to hypoglossal-facial anastomosis (HFA) without being clearly shown. We have compared patients with a peripheral facial paralysis at those with HFA. AIMS OF THE STUDY: Retrospective study comparing verbal communication (articulation) and non-verbal within two groups of patients: patients with patient FP versus with HFA. PATIENTS AND METHODS: 10 patients with idiopathic FP versus 7 patients with HFA took part in this study. The series of tests includes an evaluation of the motor possibilities, bilabial pressure measurement (for the patients with FP), speech capacities and finally an evaluation of the verbal and non-verbal communication from a scale of satisfaction. RESULTS: The results highlight: the presence of real speech disorders (permanent) among patients with FP and their absence among patients having profited from HFA; a real satisfaction of the HFA versus FP on the quality of life compared to daily tasks, more specifically concerning verbal and food skills. CONCLUSION: The HFA is not responsible for speech disorders, and makes undeniable improvements confirmed subsequently by the patients.

[Parapharyngeal chondrosarcoma and Ollier's disease: a case report and review of the literature]. / Chondrosarcome para-pharyngé et maladie d'Ollier.

OBJECTIVES: Ollier's disease is a constitutional pathology of unknown etiology. It is characterized by bone dysplasia generating numerous enchondromas. The malignant degeneration of this dysplasia is well known. The aim of this article is to study the diagnostic, therapeutic and prognostic characteristics of these lesions. MATERIAL AND METHODS: We report a case of parapharyngeal chondrosarcoma extended to the base of the skull in a patient with Ollier's disease. The treatment was a surgical removal by a cervicotransoral incision combined with a preauricular incision and with a mastoidectomy. It was therefore possible to control the skull base, the parapharyngeal space, the infratemporal fossa and the major neurovascular structures. The removal of the lesion was completed at the level of the clivus and sphenoid with optics (30 and 70 degrees ). We discuss this treatment and the follow up on the bases of literature data. RESULTS: The neoplastic degeneration of enchondromas is estimated between 25 to 50% of cases. The most frequent location is the pelvic bones. Chondrosarcomas are slow growing tumors and their metastatic potential is less significant as we note it in our case report. Their diagnostic is essentially based on histological criteria's and their treatment is surgical. CONCLUSION: Chondrosarcomas of the ENT area occurring with Ollier's disease is rare. Their prognostic is good if the surgical treatment is well done.

[Treatment of Bell's palsy with acyclovir and methylprednisolone]. / Traitement des paralysies faciales idiopathiques par méthylprednisolone et aciclovir.

OBJECTIVE: An open therapeutic trial was conducted in patients with Bell's palsy. Results were compared with data in the literature. MATERIALS AND METHODS: Between 1997 and 2000, 76 patients with Bell's palsy were treated with intravenous methylprednisolone (2 mg/kg/day) and acyclovir (5-10 mg/kg/8 hours) for 7 days. Treatment was initiated in all patients before the 14th day of illness. Severity of the palsy was scored on the first day of treatment and again one year later using the House and Brackman scale. RESULTS: Grade II or III palsy were observed in 38% of the patients at initial presentation, grades IV to VI in 62%. After treatment, 92% of the patients had reverted to grades I and II (good outcome) and only 8% had sequelae at 1-year follow-up. All patients with initial grade I or II recovered completely. For patients with grade IV, V, or VI complete recovery at 1 year was observed in 94, 86 and 50% respectively. CONCLUSION: Data in the literature suggest that corticosteroids should improve recovery in Bell's plasy. In our study, adjunction of acyclovir did not demonstrate any clear improvement in the cure rate. Benefit could depend on early prescription.

Midbrain deafness with normal brainstem auditory evoked potentials.

The authors report two cases of patients with word deafness. The word deafness occurred after a head injury for the first patient and after an arterio venous malformation embolization for the second patient. MRI demonstrated bilateral lesions of the inferior colliculi but brainstem auditory-evoked potentials (BAEP) were within normal limits. These cases demonstrated that lesions involving the two inferior colliculi induced pure word deafness but do not affect BAEP.

No evidence of measles virus in stapes samples from patients with otosclerosis.

Otosclerosis is a localized bone dystrophy of unknown etiology mainly involving the stapes. The hypothesis of a persistent infection by the measles virus was based on the inconstant detection of the virus by various methods, including reverse transcription-PCR (RT-PCR) of patients' stapes samples. The aim of this work was to investigate the presence of the measles virus in stapedial otosclerosis foci by different sensitive methods. Pathologic stapes samples were obtained from 35 patients suffering from otosclerosis. Measles virus detection was performed by (i) cocultures of Vero cells and primary cell cultures of bone samples (n = 7), (ii) immunofluorescence study of these cocultures (n = 3), and (iii) RT-PCR on RNA directly obtained from fresh frozen samples (n = 28) and on RNA extracted from the primary cell cultures (n = 2). Viral genomic regions coding for N (nucleoprotein) and M (matrix) proteins were separately amplified. PCR sensitivity was optimized on the measles virus Edmonston strain. Glyceraldehyde-3-phosphate dehydrogenase mRNA was used as a marker of total RNA recovery. PCR products were tested by Southern blot hybridization technique to improve sensitivity and specificity. PCRs amplifying the M and the N protein genes were able to detect the control measles virus RNA at titers as low as 0.1 and 0.01 50% tissue culture infective dose, respectively. With these highly sensitive methods, we could not evidence the presence of the measles virus in any of our bone samples or primary bone cell cultures. Our results do not confirm the hypothesis of persistent measles virus infection in otosclerosis.

Further evidence for a central reorganisation of synaptic connectivity in patients with hypoglossal-facial anastomosis in man.

In normal subjects, electrical stimulation of trigeminal mucosal afferents (lingual nerve - V3) can elicit a short latency (12.5+/-0. 3 ms; mean+/-S.D.) reflex response in the ipsilateral genioglossus muscle (Maisonobe et al., Reflexes elicited from cutaneous and mucosal trigeminal afferents in normal human subjects. Brain Res. 1998;810:220-228). In the present study on patients with hypoglossal-facial (XII-VII) nerve anastomoses, we were able to record similar R1-type blink reflex responses in the orbicularis oculi muscles, following stimulation of either supraorbital nerve (V1) or lingual nerve (V3) afferents. However, these responses were not present in normal control subjects. Voluntary swallowing movements produced clear-cut facilitations of the R1 blink reflex response elicited by stimulation of V1 afferents. In a conditioning-test procedure with a variable inter-stimulus interval, the R1 blink reflex response elicited by supraorbital nerve stimulation was facilitated by an ipsilateral mucosal conditioning stimulus in the V3 region. This facilitatory effect was maximal when the two stimuli (conditioning and test) were applied simultaneously. This effect was not observed on the R1 component of the blink reflex in the normal control subjects. These data strongly suggest that in patients with XII-VII anastomoses, but not in normal subjects, both cutaneous (V1) and mucosal (V3) trigeminal afferents project onto the same interneurones in the trigeminal principal sensory nucleus. This clearly supports the idea that peripheral manipulation of the VIIth and the XIIth nerves induces a plastic change within this nucleus.

Combined intratumor cisplatinum injection and Nd:YAG laser therapy.

OBJECTIVES/HYPOTHESIS: Interstitial laser therapy (ILT) has become useful for tumor palliation in patients with advanced head and neck cancer. Cisplatinum chemotherapy also is a frequent adjuvant treatment for recurrent tumors, but systemic toxicity limits application. Intratumor cisplatinum injection combined with ILT may improve therapy of these recurrent tumors with reduced toxicity. STUDY DESIGN: Prospective. Tumor transplants were injected with cisplatinum in a gel implant before ILT to evaluate treatment response and toxicity in a preclinical study. METHODS: UCLA-P3 human squamous cell carcinoma tumors were grown as subcutaneous transplants in nude mice and treated by intratumor injection of 2 mg/mL cisplatinum in a slow-release, collagen-based gel carrier 4 hours before interstitial implantation of Nd:YAG laser fiberoptics to induce local tumor hyperthermia. Treatment efficacy and toxicity were followed for 12 weeks after combined drug and laser therapy compared with ILT alone. RESULTS: Combined cisplatinum gel and ILT was a significant improvement (P < .01 by chi-square test) and induced 57% complete responses without regrowth in 21 transplanted tumors compared with only 24% in 21 tumors after ILT alone during 12-week follow-up. Recurrences in both cases appeared to result from nonuniform laser energy delivery within tumors via the implanted fiberoptic tip. CONCLUSIONS: The results of this experimental combined cisplatinum and ILT study suggest it may be possible to improve treatment of advanced head and neck cancer by intratumor injection of gel implants containing the drug followed by interstitial Nd:YAG laser hyperthermia.

Reflexes elicited from cutaneous and mucosal trigeminal afferents in normal human subjects.

It has been shown that in patients in whom the central stump of the hypoglossal nerve has been anastomosed to the peripheral stump of a lesioned facial nerve, supraorbital nerve stimulation can elicit a short-latency reflex (12.5+/-0.6 ms; mean+/-S.D.) in facial muscles similar to the R1 disynaptic blink reflex response, but not followed by an R2 blink reflex component46. Thus in addition to replacing the facial neurons at peripheral synapses, these hypoglossal nerves contribute to a trigemino-hypoglossal reflex. The aim of this work was to study the type of reflex activities which can be elicited in both facial and tongue muscles by electrical stimulation of cutaneous (supraorbital nerve) or mucosal (lingual nerve) trigeminal (V) afferents in normal subjects. The results show that although stimulation of cutaneous V1 afferents elicits the well-known double component (R1-R2) blink reflex response in the orbicularis oculi muscles, it does not produce any detectable reflex response in the genioglossus muscle, even during experimental paradigms designed to facilitate the reflex activity. Conversely, stimulation of mucosal V3 afferents can elicit a single reflex response of the R1 type in the genioglossus muscle but not in the orbicularis oculi muscles, even during experimental paradigms designed to facilitate the reflex activity. These data are discussed in terms of two similar but separate circuits for the R1 responses of cutaneous (blink reflex) and mucosal (tongue reflex) origins. They suggest that in patients with hypoglossal-facial (XII-VII) nerve anastomosis, the short-latency trigemino-'hypoglossal-facial' reflex of the R1 blink reflex type observed in facial muscles following supraorbital nerve stimulation could be due to changes in synaptic effectiveness of the central connectivity within the principal trigeminal nucleus where both cutaneous and mucosal trigeminal afferents project.

Palliative laser therapy for recurrent head and neck cancer: a Phase II clinical study.

OBJECTIVES: Laser therapy is becoming a more precise, minimally invasive alternative for tumor ablation. Recent reports confirm successful palliation of pain and functional disabilities in patients with advanced deep carcinoma of the head and neck using interstitial laser phototherapy (ILT). STUDY DESIGN, PATIENTS, AND METHODS: The current study describes an ongoing Phase II trial of neodymium/yttrium-aluminum-garnet (Nd:YAG) laser therapy for palliation of advanced head and neck cancer. A total of 40 advanced cancer patients have been entered into this protocol (25 men and 15 women). RESULTS: Nineteen of these patients had no evidence of recurrence after ILT with an average follow-up of 11 months (range, 2 to 24 mo). Currently, 19 of these patients are alive, 14 with tumor remission and six with persistent disease. A total of 79 tumor sites received ILT with 43 (54.5%) completely ablated. Stratified by tumor site, ILT led to a complete response in 21 of 24 in the oral cavity, eight of 28 neck tumors, four of 10 in skin, and 10 of 17 in other sites. The procedure was well tolerated in most cases and was repeated at intervals in patients with residual disease or recurrences for a total of 118 laser treatments (average, 2.95 treatments per patient). CONCLUSIONS: The results suggest that ILT can be performed safely and repeated as needed, and may be less costly than conventional surgery for head and neck cancer. However, additional follow-up is needed to obtain convincing evidence of long-term therapeutic benefits.

Electrophysiological determination of the site involved in generating abnormal muscle responses in hemifacial spasm.

In patients with hemifacial spasm (HFS), abnormal muscle responses due to abnormal cross-transmission are observed in facial muscles. However, the site in the facial nerve responsible for the cross-transmission remains a matter of controversy. We have developed a model in which by considering the electrophysiological parameters involved in producing the abnormal muscle response, we can determine the site of the abnormal cross-transmission within the facial nerve. This model was applied to HFS patients with three different etiologies: idiopathic, post-Bell's palsy, and post-XII-VII anastomosis. Our data show that: in idiopathic HFS, the cross-transmission may occur in the facial nerve at the level of the pontocerebellar angle; in post-Bell's palsy, it is inside the petrous bone; and in XII-VII anastomosis, it must be in the extracranial part of the facial nerve. The possible mechanisms for this cross talk are discussed in terms of ephaptic transmission or of a central hyperexcitability in the facial motor nucleus.

Laser chemotherapy of human carcinoma cells with three new anticancer drugs.

A new experimental therapy for squamous carcinoma was tested by sensitizing human tumor cells with light-sensitive anticancer drugs followed by laser illumination at visible or infrared wavelengths. The anthrapyrazole DUP-941 and the isoquinoline derivative DUP-840 were compared with the dianthraquinone hypericin. P3 human squamous carcinoma cells were incubated for 2 h with the drugs at escalating doses ranging from 5 to 100 micrograms/ml, then exposed to visible green 532-nm or infrared 1064-nm light at 300 J output from a KTP/Nd:YAG laser. Tumor cell toxicity measured by in vitro MTT viability assays was minimal after DUP-840 uptake but was slightly enhanced by infrared laser emissions. By contrast, the strong tumoricidal effects seen after DUP-941 uptake were amplified over 10-fold by 532-nm light and up to 2-fold by 1064-nm light. Hypericin-sensitized tumor cells were killed after 532 nm irradiation even at the lowest drug dose but were not affected by 1064-nm illumination. The results suggest that laser chemotherapy with drugs sensitive to photothermal energy could become a useful new treatment modality for cancer.

The concept of laser phototherapy.

Laser phototherapy and diagnosis are emerging as new tools for cancer detection and treatment. Tumor uptake of laser dyes and chemotherapy drugs followed by laser fiberoptic insertion provides a less invasive and more effective treatment option for many cancer patients. Further development will be needed to identify optimal drug and laser combinations before this new approach becomes clinically useful.

Hypericin: a new laser phototargeting agent for human cancer cells.

Laser activation of anthracycline-related drugs combines chemotherapy with photoablation for improved treatment. Hypericin, a structurally related anthraquinone, was tested for laser activation and cytotoxicity in human cancer cells. Viability of P3 squamous cell carcinoma cells incubated with 1 to 20 microgram/mL hypericin was reduced by more than 95% after 1 minute exposure at 4 degrees C to an argon laser (514 nm, 5 W), a KTP-532 laser (532 nm, 5 W), or a 20-A xenon lamp. Viability was reduced over 90% in six human carcinoma, sarcoma, and melanoma cell lines by this combined treatment, but only trace toxicity was seen after separate exposure to hypericin or light alone. These results show that hypericin is a sensitive agent for phototherapy of human cancer cells in vitro and indicate that this drug may be useful for tumor targeting via minimally invasive imaging-guided laser fiber optics.

Laser photochemotherapy with anthracyclines on cultured human squamous carcinoma cells.

A new treatment for cancer has been tested in vitro using light-sensitive anthracyclines followed by laser photoactivation, as described by several investigators. We previously reported 10-fold enhanced laser killing after 2 hours of incubation with daunomycin by cultured human carcinoma cells. This short-term uptake leads to drug localization in cytoplasmic and membrane sites prior to nuclear accumulation and topoisomerase inhibition. In the present study, daunomycin was incubated for 2 or 24 hours with P3 squamous carcinoma cells to directly compare cytoplasmic vs. nuclear drug targeting before and after KTP-532 laser activation. Monolayer cultures of the P3 cells sensitized with daunomycin for 2 hours, then chilled (4 degree C), and exposed to the KTP laser (532 nm, 94.2 J/cm2) had a 2- to 10-fold increased therapeutic response compared with drug or laser alone when measured by MTT tetrazolium assays. After 24 hours of incubation with daunomycin, the chemotherapeutic response of P3 tumor cells was amplified 2-fold by laser exposure. The results suggest that daunomycin and laser treatment can be combined for improved therapy of human cancer.

Dynamic MRI-guided interstitial laser therapy: a new technique for minimally invasive surgery.

Interstitial laser therapy (ILT) is a promising therapeutic technique in which laser energy is delivered percutaneously to various depths in tissue. In this study, the authors compared high-speed magnetic resonance imaging (MRI) of ILT in tissues during treatment with post-treatment histopathologic specimens. The use of 5-second MRI scans allowed detection of thermal damage by the 1064-nm neodymium:yttrium-aluminum-garnet laser in ex vivo liver and brain tissues. These tissues were treated by ILT with 20 W of laser output for 5 to 30 seconds via a 600-microns fiberoptic inserted 1 cm into the specimens at a power density of 7 kW/cm2 at the tip of the bare fiber. Sequential MRI measurements of lesion areas made during and after treatment were compared to measurements of laser-induced tissue damage in histopathologic sections. Fast MRI scans and tissue histology both demonstrated increased lesion size with time of ILT. Serial images obtained during ILT detected thermal changes as areas of low signal intensity that exceeded the size of the post-treatment lesions as measured on either final MRI or histology. The thermal effects detectable by these high-speed MRI sequences can be used to monitor laser-induced tissue changes during therapy, thereby providing a valuable noninvasive method for the intraoperative assessment of heat distribution during ILT.

Interstitial laser photochemotherapy with new anthrapyrazole drugs for the treatment of xenograft tumors.

Photodynamic therapy (PDT) with lasers and new dyes has gained popularity in recent years as a minimally invasive technique with high tumoricidal effects in vitro and in some cancer patients. However, because new laser dyes are not FDA approved at present, the clinical evaluation of PDT may be years away. During the past 6 years we have used laser alone for photothermal ablation in both preclinical studies and in a large number of patients with an observed 60% tumor response rate. The 40% treatment failure led us to explore the possibility of combined therapy with lasers and standard chemotherapeutic drugs. We have recently tested a promising preclinical alternative using implantation of a bare 600-microns KTP 532 laser fiberoptic in multiple tumor sites 30 min after intratumor injection of the anthrapyrazole DUP-941. As a control, this drug was injected in 3 sites of P3 human squamous cell tumor transplants in nude mice, which led to tumor stasis without regression. Similar 400-600 mm3 tumors exposed to laser illumination alone (0.8 W for 5 sec) at multiple sites resulted in tumor regrowth after 10 weeks in 80% of the animals. However, combining interstitial laser illumination with intratumor DUP-941 injections led to complete tumor regression in 85% of the mice. We propose that intratumor drug injection followed by interstitial laser fiberoptic treatment represents a potentially useful new method for tumor ablation in advanced cancer patients.

Partial restoration of blink reflex function after spinal accessory-facial nerve anastomosis.

Functional motor control requires perfect matching of the central connections of motoneurons with their peripheral inputs. It is not known, however, to what extent these central circuits are influenced by target muscles, either during development or after a lesion. Surgical interventions aimed at restoring function after peripheral nerve lesions provide an opportunity for studying this interaction in the mature human nervous system. A patient was studied in whom the spinal accessory nerve was anastomosed into a lesioned facial nerve, allowing voluntary contractions of the previously paralysed muscles. This procedure, in addition to replacing the facial neurons at peripheral synapses, allowed a new short latency trigeminospinal accessory reflex of the R1 blink reflex type to be demonstrated, implying that trigeminal neurons had sprouted towards spinal accessory motoneurons over a distance of at least 1 cm. These results show an unexpected influence of the periphery in remodelling central connectivity in humans. The motoneuronal excitability for this R1 reflex response was therefore studied to compare the convergent properties of facial motoneurons (normal side) with those of the spinal accessory motoneurons (operated side) using a classic double shock technique with variable interstimulus intervals (conditioning test stimulus). On the normal side, conditioning stimuli (to the ipsilateral or contralateral infraliminar supraorbital nerve) produced a clearcut facilitation of the R1 blink reflex when the interstimulus interval was 30-80 ms. By contrast, a similar procedure had no effect on the R1 blink reflex mediated via the trigeminal-spinal accessory reflex arc. These data indicate that despite the heterotopic sprouting of some axons from neurons in the XIth nucleus, motoneurons involved in the newly formed reflex arc remain totally inexcitable by other trigeminal afferents and seem unable to ensure a physiological functioning of the normal blink reflex. Thus the functional relevance of the recovered R1 blink response remains unclear.