Current Treatment Options for Bilateral Vocal Fold Paralysis: A State-of-the-Art Review

Vocal fold paralysis (VFP) refers to neurological causes of reduced or absent movement of one or both vocal folds. Bilateral VFP (BVFP) is characterized by inspiratory dyspnea due to narrowing of the airway at the glottic level with both vocal folds assuming a paramedian position. The primary objective of intervention for BVFP is to relieve patients’ dyspnea. Common clinical options for management include tracheostomy, arytenoidectomy and cordotomy. Other options that have been used with varying success include reinnervation techniques and botulinum toxin (Botox) injections into the vocal fold adductors. More recently, research has focused on neuromodulation, laryngeal pacing, gene therapy, and stem cell therapy. These newer approaches have the potential advantage of avoiding damage to the voicing mechanism of the larynx with an added goal of restoring some physiologic movement of the affected vocal folds. However, clinical data are scarce for these new treatment options (i.e., reinnervation and pacing), so more investigative work is needed. These areas of research are expected to provide dramatic improvements in the treatment of BVFP.

Electro-acupuncture upregulates CGRP expression after rat spinal cord transection.

Calcitonin gene-related peptide (CGRP) plays a variety of important roles within the nervous system. Increasing CGRP expression could improve the survival of injured neurons and prevent neuronal loss. In this study, we first evaluated in vitro the neuroprotective function of CGRP on mechanically injured cerebellar granule neurons (CGNs) of rats. We then verified this result through exogenous administration of CGRP in a spinal cord transected completely in rats. Finally, we investigated the effect of electro-acupuncture (EA) on CGRP expression following the spinal cord transected completely in rats. We found that EA can improve CGRP expression, and exogenous CGRP may promote the survival of injured neurons, both in vivo and in vitro. Our results suggest that CGRP may be a specific neuropeptide expressed in GV-EA treatment of spinal cord injuries (SCI), and that CGRP may play a neuroprotective role in survival of neurons injured mechanically.

Ablative procedures for chronic pain.

The advent of neuroaugmentative techniques has reduced the application of neuroablative procedures, especially as regards pain of functional origin. Although intracranial ablative procedures are now rarely performed, spinal ablative procedures, such as anterolateral cordotomies or midline myelotomies, remain important in the management of cancer pain. These procedures produce immediate and satisfactory pain relief with acceptable complication rates. An important future trend will be the application of radiosurgery guided by functional imaging (eg,fMRI, PET) to place such intracranial lesions as cingulotomies or medial thalamotomies.

The roles of pathways in the spinal cord lateral and dorsal funiculi in signaling nociceptive somatic and visceral stimuli in rats.

The spinothalamic tract (STT) is a major ascending nociceptive pathway, interruption of which by cordotomy is used for pain relief, whereas the dorsal column (DC) pathway is usually not considered to be involved in pain transmission. However, recent clinical studies showed good relief of visceral pain in cancer patients after a DC lesion. Electrophysiological recordings in animals suggest that the analgesic effect is due to interruption of axons ascending from postsynaptic dorsal column (PSDC) neurons located in the vicinity of the central canal. In this behavioral study, we used a decrease in exploratory activity in rats after a noxious stimulus as an indicator of perceived pain, independent of withdrawal reflexes. Intradermal capsaicin injection almost abolished exploratory activity in naïve animals or in rats after a DC lesion, but did not change it in rats after ipsilateral dorsal rhizotomy or a lesion of the lateral funiculus on the side opposite to the injection. In contrast, a bilateral DC lesion counteracted the decrease in exploratory activity induced by noxious visceral stimuli for at least 180 days after the surgery. Although neurons projecting in both the STT and the PSDC path can be activated by noxious stimuli of cutaneous or visceral origin, our results suggest that the STT plays a crucial role in the perception of acute cutaneous pain and that the DC pathway is important for transmission of visceral pain.

[Contribution of thalamotomy, cordotomy and dorsal root entry zone Caudalis trigeminalis lesions in the treatment of chronic pain]. / Le rôle de la thalamotomie, de la cordotomie et de la lésion de la dorsal root entry zone (DREZ) Caudalis trigeminalis dans le traitement de la douleur chronique.

Ablative neurosurgical methods are mainly proposed in cases of nociceptive pain, but, at present, medical treatments and local pharmacotherapy (intrathecal and intracerebroventricular) are often very effective in this context. Moreover, neuropathic pain is well controlled by äugmentative techniques, except painful paroxysms. If a destructrive method is necessary, it is selective, performed according to precise neurophysiological and anatomical data with the frequent use of percutaneous and/or stereotactic techniques: the lesion of caudalis DREZ in treatment of neuropathic trigeminal pain, the antero-lateral cordotomy in the treatment of unilateral severe cancer pain and several kinds of thalamotomy.

Substance P is a possible neurotransmitter in the rat spinothalamic tract.

In order to shed some light on the neurotransmitters in the spinothalamic tract (STT), we examined, biochemically and immunohistochemically, the contents of various neurotransmitter candidates in the terminal field of the STT after cervical hemi-chordotomy (HC) and dorsal quadrant-chordotomy (dQC) in the rat. Substance P (SP), calcitonin gene-related peptide (CGRP), enkephalin, neuropeptide Y, neurotensin, oxytocin and dynorphin A were analyzed immunohistochemically. The contents of neuropeptides (SP, CGRP and cholecystokinin octapeptide) were measured by radioimmunoassay and those of amino acids (aspartic acid, glutamic acid, gamma-aminobutyric acid (GABA) and glycine) and noradrenaline were determined using high-performance liquid chromatography. Cervical hemi-chordotomy, but not dQC, caused significant decreases of the SP-like immunoreactivity in and SP content of the ventral thalamus on the ipsilateral side, compared with that on the contralateral side and of rats subjected to sham-operation. However, neither HC nor dQC resulted in any changes in the ventral thalamic contents of other putative neurotransmitters examined. These results suggest that, in rats, the STT contains SP and that SP-positive fibers run in the ventral half of the ascending spinal tract at the cervical level.

Axonal sprouting in the hemisected adult rat spinal cord.

The morphological and biochemical changes were studied in adult Sprague-Dawley rats after hemisection at the L3 spinal cord level. After survival periods of one, two and three months, fluorescent tracers, FluoroGold or rhodamine B, were implanted into the dorsal white columns of these rats at the positions of the corticospinal tract below the lesion. Following uptake of the tracer, the rats were killed and the motor cortices and spinal cords of both control and hemisected rats were analysed for positively labelled neurons. The highest number of labelled cells were found two months after hemisection. They were present in both sides of the cortices, particularly in the contralateral cortex, and also in the gray matter of the spinal cord above the hemisection. A few rats which were subjected to complete transection of the spinal cord also showed labelling of neurons in the motor cortex two months after lesion. The Protargol silver technique and the [3H]choline uptake study confirmed the presence of nerve fibres traversing the lesion site in the hemisected spinal cord. Furthermore, when the rats that had been hemisected two months earlier were subjected to a second cut at the same site, chromatolytic neurons were observed in the spinal cord as well as in the motor cortices of both sides. The hemisected rats demonstrated limited recovery in limb movement. The evidence of this study clearly shows that sprouting of nerve fibres has occurred in the lesioned adult rat spinal cord.

Treatment of cancer-related pain: when orally administered medications fail.

OBJECTIVE: To summarize the available pain-relieving interventions other than oral medications for cancer-related pain. DESIGN: The pertinent literature is reviewed, and the various options for treating pain in patients with cancer are discussed. MATERIAL AND METHODS: The appropriate situations for use of parenteral administration of opioids, spinal analgesia, neural blockade, and neurosurgical treatment are outlined, and the potential problems and complications associated with these techniques are described. RESULTS: The basic approach to the management of pain in patients with cancer is to begin treatment with less potent analgesic agents early and to progress toward use of more potent pharmaceutical agents, adjuvant drugs, and invasive procedures as needed for alleviation of pain. With parenteral administration of opioids, the dosage can be adjusted rapidly, and therapy can be continued even though a patient may have gastrointestinal dysfunction. A portable ambulatory infusion pump can be used in selected patients. The major advantage of spinal opioid analgesia is the intense analgesia provided with minimal side effects. The potential complications and the availability of treatment alternatives have limited the use of neurolytic blocks, which usually provide only temporary relief of pain. In carefully selected patients with pancreatic or other upper gastrointestinal neoplasms, however, neurolytic celiac plexus and splanchnic nerve blocks are effective. Patients who fail to respond to conservative interventions may be candidates for neurosurgical procedures, such as spinal cord, cortical, or brain-stem stimulation or neuroablative operations (most commonly, cordotomy). CONCLUSION: Cancer-related pain continues to be a major problem, and clinicians should be aware of the availability of effective treatment strategies and techniques. When orally administered medications fail to control pain or cause excessive side effects, patients should be referred to an appropriate specialist or medical center for consideration of other pain-relieving techniques.

[Treatment of pain in advanced-stage intra-abdominal neoplasms]. / Il trattamento del dolore nelle neoplasie endoaddominali in fase avanzata.

Different types of pain are present in far advanced intra-abdominal cancer, sometimes in the same site too. An accurate semeiological analysis of pain is important because different types of pain often differently respond to the available therapeutical tools. In this paper the results and the complications of the most important methods of pain management in far advanced intra-abdominal cancer are examined. Analysis of the data reveals that the association of more methods, pharmacological and non, should be a rule rather than the exception.

Chronic benign cervical pain syndromes. Surgical considerations.

The results of surgical intervention for chronic benign pain syndromes are generally poor. In this review, pertinent ablative and modulatory techniques are reviewed, with specific reference to their utility for benign pain syndromes. With the possible exception of facet rhizotomy, the ablative modalities have little role in the management of benign pain syndromes. The more extensive techniques of cordotomy, dorsal root entry zone lesioning, ganglionectomy, and rhizotomy, have erratic results and high rates of complication. No long-term studies exist to support the use of facet rhizotomy. It is minimally invasive, however, and has little morbidity. In patients with benign refractory posterior column pain, facet rhizotomy may be worth consideration. Modulatory devices may have a role in benign pain syndromes. While the use of indwelling epidural catheters remains investigational, dorsal column stimulation has been widely studied. In representative reports, significant pain relief has been observed in up to 60% of patients (mean follow-up of two years). In the carefully selected patient, this may represent a valuable therapeutic adjunct.

Substance P innervation of the rat and cat thalamus. II. Cells of origin in the spinal cord.

Evidence in the preceding paper suggests that fibers and terminals immunopositive for substance P (SP) in somatosensory thalamic nuclei are part of the spinothalamic tract (STT). In this paper, more direct evidence on this point is provided by immunocytochemistry for SP on the cervical spinal cord, alone or combined with the retrograde transport of colloidal gold-labeled wheat germ agglutinin conjugated to enzymatically inactive horseradish peroxidase (WGAapoHRP-Au). In cats and rats pretreated with colchicine and/or anterolateral chordotomy (to increase SP content in cell bodies), many small to large cell bodies are SP-immunopositive especially in laminae I and V, but also in more ventral laminae of the upper cervical cord. SP neurons are also present in the dorsolateral funiculus (in the lateral spinal nucleus, LSN, in rats) but not in the lateral cervical nucleus or in the internal basilar nucleus. In both species there is a considerable degree of overlap in the distribution of SP-positive neurons and that of STT neurons. SP immunocytochemistry in rats after WGAapoHRP-Au injection in the somatosensory thalamus reveals SP-positive STT neurons in LSN, in lamina I and in lamina V, and, to a lesser extent, in more ventral laminae. These results demonstrate that SP is a marker and/or neuromediator for some STT neurons. Together with the evidence discussed in the preceding paper, the results also suggest that SP-positive neurons may be involved in the transmission of nociceptive input.

[Neurosurgery in old age. II: CNS tumors--cerebrospinal-vascular diseases--pain surgery--conclusions]. / Neurochirurgie im Alter. Teil II: Tumoren des ZNS--zerebrospinale vaskuläre Erkrankungen--Schmerzchirurgie--Schlussfolgerungen.

The relative percentage of patients who are admitted to our clinic with benign tumours often susceptible to therapy has increased from 23% (1974) to 55% (1989). In patients over 60 years old, these are above all cranial tumours (most frequently meningiomas), whereas metastases predominate at the spinal cord. 8% of the cranial meningiomas show an apoplectiform course (mostly steal effects). On the other hand, very large cranial meningiomas causing few symptoms are particularly frequent in elderly patients (larger reserve space, reduced tendency to edema). The use of minimally damaging surgical approaches, palliative operations and possibly a cautious radicality adapted to location and extent are especially important for tumour surgery in elderly patients, especially for tumours with a low tendency to proliferate. Our own experience in vascular pathology concern arteriovenous aneurysms and the diagnosis/therapy of spontaneous intracerebral hemorrhage and space-occupying malacia in the region of the cerebrum and the cerebellum. Epidural hematomas and the spinal dural arteriovenous fistulae which often become manifest at an advanced age owing to increasing medullary venous stasis are of particular therapeutic importance in elderly patients. Depending on the situation, direct surgical elimination or treatment by selective embolization may be considered. Typical trigeminal neuralgia is especially frequent in patients over 60 years in neurosurgical treatment of very severe therapy-resistant pain. Whereas the microvascular decompression of the trigeminal roots near the pons (compression by arterial loops) is most important in younger patients, we use the minimally invasive, relatively simple percutaneous thermo-rhizotomy in the Gasserian ganglion with selective functional elimination of the thinner pain fibers in elderly patients. Ablative measures are otherwise possible, above all in nociceptive pain, whereas the stimulation of the lemniscal system is of primary significance in deafferentation pain (e.g. causalgia). Spinal stimulation in inoperable peripheral arterial occlusive disease (leg, pelvis) to improve the microcirculation is of special importance: The prospect of success is greater than 80% in Fontain stage III. We do not apply subarachnoid spinal morphine administration only in malignancies, in contrast to intraventricular morphine administration (right anterior horn). For elderly patients with very severe inoperable lumbar stenosis (mostly spondylarthritis), the dosage-controlled continuous low-dose subarachnoid administration of morphine via a subcutaneously implanted programmable pump with a reservoir is suitable in some cases. These examples show that neurosurgery may be appropriate even in elderly patients. Today, more differentiated and at the same time minimally invasive diagnostic and surgical methods are available.

[Drug and non-drug tumor pain therapy in ENT medicine]. / Medikamentöse und nicht-medikamentöse Tumorschmerztherapie in der HNO-Heilkunde.

The basic of analgesic therapy in patients with advanced cancer of the head and neck is the regular application of analgesics and adjuvant analgesics. Radiotherapy is the treatment of choice in patients suffering from severe pain by bone metastases. Analgesic-resistant pain of dura in patients with tumour infiltration of the skull base is an indication for intraventricularly application of opioids by neurosurgeon.

Chronic pain: a PET study of the central effects of percutaneous high cervical cordotomy.

We have studied 5 patients with unilateral, severe chronic pain due to cancer before and after percutaneous, ventrolateral cervical cordotomy to investigate the central effects of the procedure. The aim was to identify the functional anatomical correlates of abolishing unilateral nociceptive input to the brain. Patients were investigated by positron emission tomography using C15O2 to evaluate cerebral blood flow. Comparisons were made between the patients with unilateral pain before cordotomy and normal volunteers. These demonstrated significantly less blood flow in 3 out of 4 of the individual quadrants of the hemithalamus contralateral to the side of pain (P less than 0.01-0.05). These differences were abolished by cordotomy. Comparison of the patients before and after cordotomy showed a significant decrease in blood flow in the dorsal anterior quadrant of the thalamus contralateral to the side of pain (P less than 0.05) which was normalised after cordotomy. There were no significant changes in the prefrontal or primary somatosensory cortex. We conclude that chronic pain results in a decrease of synaptic activity at thalamic level either from decreased activity in neurones projecting to that region and/or attenuated local neuronal firing. We have demonstrated no secondary remote effects in cortex, indicating the importance of subcortical mechanisms in central responses to chronic pain.

[The current significance of spinal cord stimulation in the framework of functional neurosurgery]. / Die heutige Bedeutung der Rückenmarkstimulation (DCS) im Rahmen der funktionellen Neurochirurgie.

Spinal cord stimulation (DCS) has proved effective in different types of Deafferentation Pain. Long-term results are good in 60-85% of cases. DCS improves microcirculation and ischemia in cases of inoperable peripheral vascular diseases. Advantages of this method are: Absence of severe complications and estimation of the effect during the test phase. - Nevertheless, other neurosurgical possibilities (destructive pain surgery, spinal/cerebral application of medicaments) continue to preserve their indications.