Electrical stimulation of the trigeminal tract in chronic, intractable facial neuralgia

In this paper the treatment of patients with chronic, intractable trigeminal neuralgia by invasive electrical stimulation of the Gasserion ganglion is reviewed. Two different surgical techniques are employed in this treatment. Most frequently, a method similar to the traditional technique for percutaneous glycerol and radiofrequency trigeminal rhizolysis is used: a small percutaneous stimulation electrode is advanced under fluoroscopic control through a thin needle via the foramen ovale to the Gasserian cistern. Some neurosurgeons use an open surgical technique by which the Gasserian ganglion is approached subtemporally and extradurally, and the bipolar pad electrode is sutured to the dura. When percutaneous test stimulation is successful (at least 50% pain relief) the electrode is internalized and connected to a subcutaneous pulse generator or RF-receiver. Data from 8 clinical studies, including 267 patients have been reviewed. Of all 233 patients with medication-resistant atypical trigeminal neuralgia 48% had at least 50% long term pain relief. The result of test stimulation is a good predictor of the long term effect, because 83% of all patients with successful test stimulation had at least 50% long term relief, and 70% had at least 75% long term relief. Patients generally preferred this invasive method over TENS. The success rate in patients with postherpetic trigeminal neuralgia was very low (less than 10%). It is suggested that the likelihood of pain relief by electrical stimulation is inversely related to the degree of sensory loss. It is concluded that invasive stimulation of the Gasserian ganglion is a promising treatment modality for patients with chronic, intractable, atypical trigeminal neuralgia.     

Low back pain in the workman in Canada.

Groups of 25 Workmen''s Compensation Board patients (WCP group) and 25 non-Workmen''s Compensation Board patients (NWCP group) hospitalized because of low back pain were compared. The WCP group had a significantly higher male:female ratio, incidence of sudden onset and precipitating factors, and prevalence of weakness, decreased reflexes and sensory loss. Surgical treatment and multiple operations were significantly more frequent in the WCP group, as was complete long-term relief or worsening after operation. Adequate partial relief was significantly more frequent in the NWCP group. The differences suggest more severe conditions in the workmen. Prevalence of psychological factors was not significantly different, although a trend was observed for this to be greater in the WCP group.     

Percutaneous Radiofrequency Trigeminal Gangliolysis in the Treatment of Tic Douloureux

The treatment of tic douloureux was dramatically altered in 1962 with the demonstration that carbamazepine (Tegretol®) alone or in combination with diphenylhydantoin sodium (Dilantin®) was effective in controlling the painful paroxysms. However, 30 percent of the patients so treated have not been successfully managed and some type of surgical therapy is required to control their pain. A wide variety of surgical alternatives are available but they all trade a sensory deficit for pain relief and have a significant risk of morbidity and mortality.Experience with percutaneous radiofrequency trigeminal gangliolysis has indicated that this new technique is capable of producing lasting relief of tic douloureux in as many as 95 percent of the patients. To date there have been no deaths from this procedure and a very low incidence of minor complications. It achieves this high success rate at the expense of only partial sensory deficits restricted to a circumscribed area of the face. No other surgical alternative carries such a high long-term success rate with a low complication rate. We believe that percutaneous radiofrequency trigeminal gangliolysis has become the surgical treatment of choice for tic douloureux.     

Long-term Ventricular Pacing in Treatment of Sinoatrial Block

Six patients with symptoms due to sinoatrial block are described in whom no relief or improvement in block occurred when they were treated with isoprenaline or ephedrine. All six patients were treated by ventricular cardiac pacing with complete relief of symptoms. Despite the theoretical disadvantages of parasystole and loss of accrochage in treating these patients by ventricular pacing they have survived for periods of 18 months to over five years.     

Peripheral neuropathy does not alter the fractal dynamics of stride intervals of gait.

The purpose of this study was to determine the effect (if any) of significant sensory loss on the long-range correlations normally observed in the stride intervals of human gait. Fourteen patients with severe peripheral neuropathy and 12 gender-, age-, height-, and weight-matched nondiabetic controls participated. Subjects walked around an approximately 200-m open-level walkway for 10 min at their comfortable pace. Continuous knee joint kinematics were recorded and used to calculate a stride interval time series for each subject. Power spectral density and detrended fluctuation analyses were used to determine whether these stride intervals exhibited long-range correlations. If the loss of long-range correlations indicates deterioration of the central control of gait, then changes in peripheral sensation should have no effect. If instead the loss of long-range correlations is a consequence of a general inability to regulate gait cycle timing, then a similar loss should occur in patients with peripheral locomotor disorders. Both power spectral density analyses and detrended fluctuation analyses showed that temporal correlations in the stride times of neuropathic and control subjects were statistically identical (P = 0.954 and P = 0.974, respectively), despite slower gait speeds (P = 0.008) and increased stride time variability (P = 0.036) among the neuropathy patients. All subjects in both groups exhibited long-range correlations. These findings demonstrate that the normal long-range correlation structure of stride intervals is unaltered by significant peripheral sensory loss. This further supports the hypothesis that the central nervous system is involved in the regulation of long-range correlations.     

Sulfite intolerance: A cause of tinnitus?

Tinnitus is a common disorder characterized by a ringing or buzzing in the ear, and is poorly understood. Recent studies have linked tinnitus with impairment of the nucleus accumbens, an area of the brain responsible for filtering sensory information. It is hypothesized that in individuals with sulfite intolerance, elevated serum sulfite levels inhibit enzymes related to the synthesis or activation of neurotransmitters active in the nucleus accumbens, resulting in tinnitus. Avoidance of sulfites in food and drugs may potentially bring relief to sulfite intolerant patients experiencing tinnitus, hyperacusis or other illnesses associated with decreased dopaminergic or serotonergic activity.     

Nerve decompression at the wrist in patients with Charcot-Marie-Tooth disease

Studies evaluating the effects of nerve release in patients with Charcot-Marie-Tooth disease have been extremely limited to date. This series attempts to evaluate the clinical and electrophysiologic effect of nerve release at the wrist in a series of patients with this disease. Five patients with documented Charcot-Marie-Tooth disease of the upper extremity were followed clinically and had nerve conduction testing both before and after surgery. This study shows that there was an improvement in both sensory and motor testing after release in a significant proportion of patients (p < 0.05). All patients documented improvement in their sensory latency response postoperatively (100 percent) and most showed improvement in motor latency responses (87 percent). More importantly, however, there seems to be an even greater clinical improvement in preoperative complaints (e.g., paresthesia and pain) in the majority of the extremities that underwent surgery with all patients experiencing initial relief and the majority showing no recurrence (63 percent) at last follow-up. From these results, this relief can be variable, but has lasted for a significant duration postoperatively in the majority, necessitating careful consideration for surgery as a legitimate option for patients with Charcot-Marie-Tooth.     

A prospective study to assess the outcome of steroid injections and wrist splinting for the treatment of carpal tunnel syndrome

Surgery is the definitive treatment for carpal tunnel syndrome. Conservative treatments, such as wrist splinting and steroid injections, are also effective for the relief of carpal tunnel symptoms, but their use remains controversial because they only offer long-term relief in a minority of patients. A prospective study was performed to assess the role of steroid injections combined with wrist splinting for the management of carpal tunnel syndrome. A total of 73 patients with 99 affected hands were studied. Patients presenting with known medical causes or muscle wasting were excluded. Diagnosis was made clinically and electrodiagnostic studies were performed only when equivocal clinical signs were present. Each patient received up to three betamethasone injections into the carpal tunnel and wore a neutral-position wrist splint continuously for 9 weeks. After that period, symptomatic patients received an open carpal tunnel release, and those who remained asymptomatic were followed up regularly for at least 1 year. Patients who relapsed were scheduled for surgery. At a minimum follow-up of 1 year, seven patients (9.6 percent) with 10 affected hands (10.1 percent) remained asymptomatic. This group had a significantly shorter duration of symptoms (2.9 months versus 8.35 months; p = 0.039, Mann-Whitney test) and significantly less sensory change (40 percent versus 72 percent; p = 0.048, Fisher's exact test) at presentation when compared with the group who had surgery. It is concluded that steroid injections and wrist splinting are effective for relief of carpal tunnel syndrome symptoms but have a long-term effect in only 10 percent of patients. Symptom duration of less than 3 months and absence of sensory impairment at presentation were predictive of a lasting response to conservative treatment. It is suggested that selected patients (i.e., with no thenar wasting or obvious underlying cause) presenting with mild to moderate carpal tunnel syndrome receive either a single steroid injection or wear a wrist splint for 3 weeks. This will allow identification of the 10 percent of patients who respond well to conservative therapy and do not need surgery.     

Signaling by sensory receptors

Sensory systems detect small molecules, mechanical perturbations, or radiation via the activation of receptor proteins and downstream signaling cascades in specialized sensory cells. In vertebrates, the two principal categories of sensory receptors are ion channels, which mediate mechanosensation, thermosensation, and acid and salt taste; and G-protein-coupled receptors (GPCRs), which mediate vision, olfaction, and sweet, bitter, and umami tastes. GPCR-based signaling in rods and cones illustrates the fundamental principles of rapid activation and inactivation, signal amplification, and gain control. Channel-based sensory systems illustrate the integration of diverse modulatory signals at the receptor, as seen in the thermosensory/pain system, and the rapid response kinetics that are possible with direct mechanical gating of a channel. Comparisons of sensory receptor gene sequences reveal numerous examples in which gene duplication and sequence divergence have created novel sensory specificities. This is the evolutionary basis for the observed diversity in temperature- and ligand-dependent gating among thermosensory channels, spectral tuning among visual pigments, and odorant binding among olfactory receptors. The coding of complex external stimuli by a limited number of sensory receptor types has led to the evolution of modality-specific and species-specific patterns of retention or loss of sensory information, a filtering operation that selectively emphasizes features in the stimulus that enhance survival in a particular ecological niche. The many specialized anatomic structures, such as the eye and ear, that house primary sensory neurons further enhance the detection of relevant stimuli.     

Multiple sclerosis and neuro-ophthalmologic manifestations

The authors report clinical features of ocular manifestations in patients with multiple sclerosis (MS), those that affect the visual sensory system and those that affect the ocular motor system. Disturbances of visual sensory function may precede, manifest coincidentally or follow the neurologic manifestations. Visual disturbances are common in MS and often a result of acute demyelinating optic neuropathy. Careful examination of MS patients, who have never suffered optic neuritis, may also reveal asymptomatic visual loss. Asymptomatic visual loss seems to be a universal feature of MS. Patients with multiple sclerosis may develop disorders of fixation, ocular motility and ocular alignment. Disorders of ocular motor system are frequently the initial sign of multiple sclerosis and occur as its presenting sign weeks, month, or years before other neurologic symptoms and signs develop.     

Combined electrical stimulation of the periaqueductal gray matter and sensory thalamus

11 patients with chronic intractable pain of at least 3 years' duration underwent a morphine infusion test, the results of which suggested a syndrome of superimposed somatogenic and neurogenic pain components. They then underwent stereotactic implantation of a dual-channel brain stimulation system with two brain electrodes, one in the left periaqueductal gray matter (PAG) and the other in the sensory thalamus contralateral to the neurogenic pain. Using this system, all patients have obtained excellent simultaneous relief of both pain components (follow-up 12-36 months). The findings support a notion of two separate sensory modulating systems. They indicate that combined electrical stimulation of the PAG and sensory thalamus is a technically feasible and clinically satisfactory modality for the control of pain in humans, and they appear to indicate that better pain control is obtained by continuous, cycled stimulation of the PAG than by the conventional mode of stimulation.     

Somatosensory profiles but not numbers of somatosensory abnormalities of neuropathic pain patients correspond with neuropathic pain grading

Due to the lack of a specific diagnostic tool for neuropathic pain, a grading system to categorize pain as 'definite', 'probable', 'possible' and 'unlikely' neuropathic was proposed. Somatosensory abnormalities are common in neuropathic pain and it has been suggested that a greater number of abnormalities would be present in patients with 'probable' and 'definite' grades. To test this hypothesis, we investigated the presence of somatosensory abnormalities by means of Quantitative Sensory Testing (QST) in patients with a clinical diagnosis of neuropathic pain and correlated the number of sensory abnormalities and sensory profiles to the different grades. Of patients who were clinically diagnosed with neuropathic pain, only 60% were graded as 'definite' or 'probable', while 40% were graded as 'possible' or 'unlikely' neuropathic pain. Apparently, there is a mismatch between a clinical neuropathic pain diagnosis and neuropathic pain grading. Contrary to the expectation, patients with 'probable' and 'definite' grades did not have a greater number of abnormalities. Instead, similar numbers of somatosensory abnormalities were identified for each grade. The profiles of sensory signs in 'definite' and 'probable' neuropathic pain were not significantly different, but different from the 'unlikely' grade. This latter difference could be attributed to differences in the prevalence of patients with a mixture of sensory gain and loss and with sensory loss only. The grading system allows a separation of neuropathic and non-neuropathic pain based on profiles but not on the total number of sensory abnormalities. Our findings indicate that patient selection based on grading of neuropathic pain may provide advantages in selecting homogenous groups for clinical research.     

Sensory Neurons Do Not Induce Motor Neuron Loss in a Human Stem Cell Model of Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is an autosomal recessive disorder leading to paralysis and early death due to reduced SMN protein. It is unclear why there is such a profound motor neuron loss, but recent evidence from fly and mouse studies indicate that cells comprising the whole sensory-motor circuit may contribute to motor neuron dysfunction and loss. Here, we used induced pluripotent stem cells derived from SMA patients to test whether sensory neurons directly contribute to motor neuron loss. We generated sensory neurons from SMA induced pluripotent stem cells and found no difference in neuron generation or survival, although there was a reduced calcium response to depolarizing stimuli. Using co-culture of SMA induced pluripotent stem cell derived sensory neurons with control induced pluripotent stem cell derived motor neurons, we found no significant reduction in motor neuron number or glutamate transporter boutons on motor neuron cell bodies or neurites. We conclude that SMA sensory neurons do not overtly contribute to motor neuron loss in this human stem cell system.     

Electrical stimulation of the posterior limb of the internal capsule for treatment of thalamic pain

Electrical stimulation of the posterior limb of the internal capsule was performed in 7 patients with thalamic pain who had developed dysesthesia, hyperpathia and/or spontaneous burning pain. Ramped bipolar stimulation elicited sensory responses, such as warm or comfortable sensation. Follow-up from 9 months to 2 years and 7 months showed that 3 patients had a good result, two had fair and the remaining two had poor results. No serious side effects were seen. The mechanism of pain relief by the internal capsule stimulation is discussed.     

Dental topography of platyrrhines and prosimians: Convergence and contrasts

Dental topographic analysis is the quantitative assessment of shape of three‐dimensional models of tooth crowns and component features. Molar topographic curvature, relief, and complexity correlate with aspects of feeding behavior in certain living primates, and have been employed to investigate dietary ecology in extant and extinct primate species. This study investigates whether dental topography correlates with diet among a diverse sample of living platyrrhines, and compares platyrrhine topography with that of prosimians. We sampled 111 lower second molars of 11 platyrrhine genera and 121 of 20 prosimian genera. For each tooth we calculated Dirichlet normal energy (DNE), relief index (RFI), and orientation patch count (OPCR), quantifying surface curvature, relief, and complexity respectively. Shearing ratios and quotients were also measured. Statistical analyses partitioned effects of diet and taxon on topography in platyrrhines alone and relative to prosimians. Discriminant function analyses assessed predictive diet models. Results indicate that platyrrhine dental topography correlates to dietary preference, and platyrrhine‐only predictive models yield high rates of accuracy. The same is true for prosimians. Topographic variance is broadly similar among platyrrhines and prosimians. One exception is that platyrrhines display higher average relief and lower relief variance, possibly related to lower relative molar size and functional links between relief and tooth longevity distinct from curvature or complexity. Explicitly incorporating phylogenetic distance matrices into statistical analyses of the combined platyrrhine‐prosimian sample results in loss of significance of dietary effects for OPCR and SQ, while greatly increasing dietary significance of RFI. Am J Phys Anthropol 153:29–44, 2014. © 2013 Wiley Periodicals, Inc.     

Loss of Olfactory Receptor Function in Hominin Evolution

The mammalian sense of smell is governed by the largest gene family, which encodes the olfactory receptors (ORs). The gain and loss of OR genes is typically correlated with adaptations to various ecological niches. Modern humans have 853 OR genes but 55% of these have lost their function. Here we show evidence of additional OR loss of function in the Neanderthal and Denisovan hominin genomes using comparative genomic methodologies. Ten Neanderthal and 8 Denisovan ORs show evidence of loss of function that differ from the reference modern human OR genome. Some of these losses are also present in a subset of modern humans, while some are unique to each lineage. Morphological changes in the cranium of Neanderthals suggest different sensory arrangements to that of modern humans. We identify differences in functional olfactory receptor genes among modern humans, Neanderthals and Denisovans, suggesting varied loss of function across all three taxa and we highlight the utility of using genomic information to elucidate the sensory niches of extinct species.     

Cell- and gene-therapy approaches to inner ear repair

Sensorineural hearing loss is the most common sensory disorder in humans. It is primarily due to the degeneration of highly specialised mechanosensory cells in the cochlea, the so-called hair cells. Hearing problems can also be caused or further aggravated by the death of auditory sensory neurons that convey the information from the hair cells to the brain stem. Despite the discovery of stem/progenitor cells in the mammalian cochlea, no regeneration of either damaged hair cells or auditory neurons has been observed in mammals, in contrast to what is seen in avians and non-mammalian vertebrates. The reasons for this divergence have not yet been elucidated, although loss of stem cells and/or loss of their phenotypic plasticity in adult mammals have been put forward as possible explanations. Given the high incidence of this disorder and its economic and social implications, a considerable number of research lines have been set up aimed towards the regeneration of cochlear sensory cell types. This review summarizes the various routes that have been explored, ranging from the genetic modification of endogenous cells remaining in the inner ear in order to promote their transdifferentiation, to the implantation of exogenous stem or progenitor cells and their subsequent differentiation within the host tissue. Prophylactic treatments to fight against progressive sensory cell degeneration in the inner ear are also discussed.     

Why do animals have so many receptors? The role of multiple chemosensors in animal perception

Many animals have an abundance and diverse assortment of peripheral sensors, both across and within sensory modalities. Multiple sensors offer many functional advantages to an animal's ability to perceive and respond to environmental signals. Advantages include extending the ability to detect and determine the spatial distribution of stimuli, improving the range and accuracy of discrimination among stimuli of different types and intensities, increasing behavioral sensitivity to stimuli, ensuring continued sensory capabilities when the probability of damage or other loss of function to some sensors is high, maintaining sensory function over the entire sensory surface during development and growth, and increasing the richness of behavioral output to sensory stimulation. In this paper, we use the crustacean chemosensory system as the primary example to discuss these functions of multiple sensors. These principles may be applicable to the function of autonomous robots and should be considered in their design.     

Death Following Inhalation of Mercury Vapor at Home.

Confusion exists among physicians over the legal requirements and appropriate prescribing of narcotics to addicted or habitual users of narcotics. The result has often been either (1) the deprivation of appropriate treatment for patients who desire detoxification or adequate pain relief, or (2) illegal prescribing by physicians. Because most narcotics are potent and dangerous substances, certain legal restrictions are necessary to protect the general public. State-approved programs have been established to prescribe methadone and propoxyphene napsylate for addiction treatment. Current laws and regulations in California permit every practicing physician to provide effective and safe treatment for addiction and pain relief.     

Fucosyl-GM1 in Human Sensory Nervous Tissue Is a Target Antigen in Patients with Autoimmune Neuropathies

Abstract: Several gangliosides of human nervous tissues have been reported to be potential target antigens in autoimmune neuropathies. To explain the diversity of clinical symptoms in patients with antiganglioside antibodies, we have searched for ganglioside antigens that are specific to individual nervous tissues such as motoneurons, peripheral motor nerves, and sensory nerves. Although the major ganglioside compositions were not different among human peripheral motor and sensory nerves, fucosyl-GM1 was found to be expressed in sensory nervous tissue but not in spinal cord, motor nerve, and sympathetic ganglia. Sera from several patients with sensory nerve involvement also reacted with fucosyl-GM1 as well as GM1. Thus, fucosyl-GM1 may be a responsible target antigen for developing sensory symptoms in some patients with autoimmune neuropathies.