Neural activity in trigeminal neuralgia patients with sensory and motor stimulations: A pilot functional MRI study.

OBJECTIVE: Trigeminal neuralgia (TN) is a neuropathic pain syndrome that typically exhibits paroxysmal pain. However, the true mechanism of pain processing is unclear. We aim to evaluate the neural activity changes, before and after radiofrequency rhizotomy, in TN patients using functional MRI (fMRI) with sensory and motor stimulations. METHODS: Six patients with classical TN participated in the study. Each patient underwent two boxcar paradigms of fMRI tasks: air-sensation and jaw-clenching around 1-3 weeks before and after the surgical intervention. McGill Pain Questionnaire (MPQ) was used to evaluate the pain intensity prior to fMRI study. RESULTS: Before rhizotomy, the jaw-clenching stimulation yielded reduced brain activation in primary motor (M1) and primary (SI) and secondary somatosensory (SII) cortices. Following intervention, activation in those regions returned to near normal levels observed in healthy subjects. For air-sensation stimulation, several pain and pain modulation regions such as right thalamus, right putamen, insula, and brainstem, were activated before the intervention, but subsided after the intervention. This correlated well with the change of MPQ scores (p < 0.01). CONCLUSIONS: In our study, we observed significant pain reduction accompanied by increased motor activities after rhizotomy in patients with TN. We hypothesize that the reduced motor activities identified in fMRI may be reversed after the treatment with radiofrequency rhizotomy. More research is warranted.

Acute Psychosis as Main Manifestation of Central Pontine Myelinolysis.

Central pontine myelinolysis (CPM) is an acute demyelinating neurological disorder affecting primarily the central pons and is frequently associated with rapid correction of hyponatremia. Common clinical manifestations of CPM include spastic quadriparesis, dysarthria, pseudobulbar palsy, and encephalopathy of various degrees; however, coma, "locked-in" syndrome, or death can occur in most severe cases. Rarely, CPM presents with neuropsychiatric manifestations, such as personality changes, acute psychosis, paranoia, hallucinations, or catatonia, typically associated with additional injury to the brain, described as extrapontine myelinolysis (EPM). We present a patient with primarily neuropsychiatric manifestations of CPM, in the absence of focal neurologic deficits or radiographic extrapontine involvement. A 51-year-old female without significant medical history presented with dizziness, frequent falls, diarrhea, generalized weakness, and weight loss. Physical examination showed no focal neurological deficits. Laboratory data showed severe hyponatremia, which was corrected rather rapidly. Subsequently, the patient developed symptoms of an acute psychotic illness. Initial brain magnetic resonance imaging (MRI) was unremarkable, although a repeat MRI two weeks later revealed changes compatible with CPM. This case demonstrates that acute psychosis might represent the main manifestation of CPM, especially in early stages of the disease, which should be taken into consideration when assessing patients with acute abnormalities of sodium metabolism.

Trigeminal and occipital peripheral nerve stimulation for craniofacial pain: a single-institution experience and review of the literature.

OBJECT: Treatment of chronic neuropathic pain in the region of the head and face presents a challenge for pain specialists; patients who do not respond to conventional treatment modalities usually continue to suffer from pain due to the lack of reliable medical and surgical approaches. Peripheral nerve stimulation (PNS) has been used to treat neuropathic pain for many decades, but only recently has it been applied systematically to the craniofacial region. To advance the study of this treatment option, the authors present their initial experience with this approach, summarize published data on the use of PNS in treatment of craniofacial pain, and discuss some technical details of the craniofacial PNS procedure. METHODS: A review of prospectively collected data in 30 patients who underwent PNS surgery for craniofacial pain was performed. The pain location, duration, cause, and previous treatments were analyzed, along with the surgical details, initial and long-term results, complications, and repeated operations. Stimulated nerves in this group included supraorbital (seven patients), infraorbital (six), and occipital (21); in 19 patients more than one nerve was stimulated. Twenty-two patients proceeded with implantation of a permanent system after the trial. Of these, at the time of the latest evaluation (mean follow-up duration 35 months), in two patients the devices had been removed because of pain improvement over time, in three the devices were removed due to loss of effectiveness (two cases) or late infection (one), and the rest are enjoying either complete (15 patients) or partial (two patients) pain relief. Three patients underwent repeated operation due to lead erosion, infection, or migration. CONCLUSIONS: Peripheral nerve stimulation appears to be a safe and effective approach in the treatment of craniofacial neuropathic pain. The growing body of literature supports a wider acceptance of this approach in the field of pain surgery.

Relative changes in cerebral blood flow and neuronal activity in local microdomains during generalized seizures.

There is broad agreement that generalized tonic-clonic seizures (GTCS) and normal somatosensory stimulation are associated with increases in regional CBF. However, the data regarding CBF changes during absence seizures are controversial. Electrophysiologic studies in WAG/Rij rats, an established animal model of absence seizures, have shown spike-wave discharges (SWD) that are largest in the perioral somatosensory cortex while sparing the visual cortex. Recent functional magnetic resonance imaging (fMRI) studies in the same model have also shown localized increases in fMRI signals in the perioral somatosensory cortex during SWD. Because fMRI signals are only indirectly related to neuronal activity, the authors directly measured CBF and neuronal activity from specific microdomains of the WAG/Rij cortex using a specially designed probe combining laser-Doppler flowmetry and extra-cellular microelectrode recordings under fentanyl/haloperidol anesthesia. Using this approach, parallel increases in neuronal activity and CBF were observed during SWD in the whisker somatosensory (barrel) cortex, whereas the visual cortex showed no significant changes. For comparison, these measurements were repeated during somatosensory (whisker) stimulation, and bicuculline-induced GTCS in the same animals. Interestingly, whisker stimulation increased neuronal activity and CBF in the barrel cortex more than during SWD. During GTCS, much larger increases that included both the somatosensory and visual cortex were observed. Thus, SWD in this model produce parallel localized increases in neuronal activity and CBF with similar distribution to somatosensory stimulation, whereas GTCS produce larger and more widespread changes. The normal response to somatosensory stimulation appears to be poised between two abnormal responses produced by two physiologically different types of seizures.

Dynamic fMRI and EEG recordings during spike-wave seizures and generalized tonic-clonic seizures in WAG/Rij rats.

Generalized epileptic seizures produce widespread physiological changes in the brain. Recent studies suggest that "generalized" seizures may not involve the whole brain homogeneously. For example, electrophysiological recordings in WAG/Rij rats, an established model of human absence seizures, have shown that spike-and-wave discharges are most intense in the perioral somatosensory cortex and thalamus, but spare the occipital cortex. Is this heterogeneous increased neuronal activity matched by changes in local cerebral blood flow sufficient to meet or exceed cerebral oxygen consumption? To investigate this, we performed blood oxygen level-dependent functional magnetic resonance imaging (fMRI) measurements at 7T with simultaneous electroencephalogram recordings. During spontaneous spike-wave seizures in WAG/Rij rats under fentanylhaloperidol anesthesia, we found increased fMRI signals in focal regions including the perioral somatosensory cortex, known to be intensely involved during seizures, whereas the occipital cortex was spared. For comparison, we also studied bicuculline-induced generalized tonic-clonic seizures under the same conditions, and found fMRI increases to be larger and more widespread than during spike-and-wave seizures. These findings suggest that even in regions with intense neuronal activity during epileptic seizures, oxygen delivery exceeds metabolic needs, enabling fMRI to be used for investigation of dynamic cortical and subcortical network involvement in this disorder.

Dysregulation of sodium channel expression in cortical neurons in a rodent model of absence epilepsy.

Due to the involvement of cortical neurons in spike-wave discharge (SWD) initiation, and the contribution of voltage-gated sodium channels (VGSCs) to neuronal firing, we examined alterations in the expression of VGSC mRNA and protein in cortical neurons in the WAG/Rij absence epileptic rat. WAG/Rij rats were compared to age-matched Wistar control rats at 2, 4, and 6 months. Continuous EEG data was recorded, and percent time in SWD was determined. Tissue from different cortical locations from WAG/Rij and Wistar rats was analyzed for VGSC mRNA (by quantitative PCR) and protein (by immunocytochemistry). SWDs increased with age in WAG/Rij rats. mRNA levels for sodium channels Nav1.1 and Nav1.6, but not Nav1.2, were found to be up-regulated selectively within the facial somatosensory cortex (at AP +0.0, ML +6.0 mm). Protein levels for Nav1.1 and Nav1.6 were up-regulated in layer II-IV cortical neurons in this region of cortex. No significant changes were seen in adjacent regions or other brain areas, including the pre-frontal and occipital cortex. In the WAG/Rij model of absence epilepsy, we identified a specific region of cortex, in layer II-IV neurons on the lateral convexity of the cortex in the facial somatosensory area, where mRNA and protein expression of sodium channel genes Nav1.1 and Nav1.6 are up-regulated. This region of cortex approximately matches the electrophysiologically determined region of seizure onset. Changes in the expression of Nav1.1 and Nav1.6 parallel age-dependent increases in seizure frequency and duration.

Early treatment suppresses the development of spike-wave epilepsy in a rat model.

PURPOSE: Current treatments for epilepsy may control seizures, but have no known effects on the underlying disease. We sought to determine whether early treatment in a model of genetic epilepsy would reduce the severity of the epilepsy phenotype in adulthood. METHODS: We used Wistar albino Glaxo rats of Rijswijk (WAG/Rij) rats, an established model of human absence epilepsy. Oral ethosuximide was given from age p21 to 5 months, covering the usual period in which seizures develop in this model (age approximately 3 months). Two experiments were performed: (1) cortical expression of ion channels Nav1.1, Nav1.6, and HCN1 (previously shown to be dysregulated in WAG/Rij) measured by immunocytochemistry in adult treated rats; and (2) electroencephalogram (EEG) recordings to measure seizure severity at serial time points after stopping the treatment. RESULTS: Early treatment with ethosuximide blocked changes in the expression of ion channels Nav1.1, Nav1.6, and HCN1 normally associated with epilepsy in this model. In addition, the treatment led to a persistent suppression of seizures, even after therapy was discontinued. Thus, animals treated with ethosuximide from age p21 to 5 months still had a marked suppression of seizures at age 8 months. DISCUSSION: These findings suggest that early treatment during development may provide a new strategy for preventing epilepsy in susceptible individuals. If confirmed with other drugs and epilepsy paradigms, the availability of a model in which epileptogenesis can be controlled has important implications both for future basic studies, and human therapeutic trials.

Current aproach to cancer pain management: Availability and implications of different treatment options.

Despite tremendous progress in medicine during last couple of decades, cancer still remains the most horrifying diagnosis for anybody due to its almost inevitable futility. According to American Cancer Society Statistics, it is estimated that only in the United States more than half a million people will die from cancer in 2006. For those who survive, probably the most fearsome symptom regardless of cancer type will be the pain. Although most pain specialists and oncologists worldwide are well aware of the importance to adequately treat the pain, it was yet established that more than half of cancer patients have insufficient pain control, and about quarter of them actually die in pain. Therefore, in this review article we attempted to provide the comprehensive information about different options available nowadays for treating cancer pain focusing on most widely used pharmacologic agents, surgical modalities for intractable pain control, their potential for adverse effects, and ways to increase the effectiveness of treatment maximally optimizing analgesic regimen and improving compliance.

Current algorithm for the surgical treatment of facial pain.

BACKGROUND: Facial pain may be divided into several distinct categories, each requiring a specific treatment approach. In some cases, however, such categorization is difficult and treatment is ineffective. We reviewed our extensive clinical experience and designed an algorithmic approach to the treatment of medically intractable facial pain that can be treated through surgical intervention. METHODS: Our treatment algorithm is based on taking into account underlying pathological processes, the anatomical distribution of pain, pain characteristics, the patient's age and medical condition, associated medical problems, the history of previous surgical interventions, and, in some cases, the results of psychological evaluation. The treatment modalities involved in this algorithm include diagnostic blocks, peripheral denervation procedures, craniotomy for microvascular decompression of cranial nerves, percutaneous rhizotomies using radiofrequency ablation, glycerol injection, balloon compression, peripheral nerve stimulation procedures, stereotactic radiosurgery, percutaneous trigeminal tractotomy, and motor cortex stimulation. We recommend that some patients not receive surgery at all, but rather be referred for other medical or psychological treatment. RESULTS: Our algorithmic approach was used in more than 100 consecutive patients with medically intractable facial pain. Clinical evaluations and diagnostic workups were followed in each case by the systematic choice of the appropriate intervention. The algorithm has proved easy to follow, and the recommendations include the identification of the optimal surgery for each patient with other options reserved for failures or recurrences. Our overall success rate in eliminating facial pain presently reaches 96%, which is higher than that observed in most clinical series reported to date CONCLUSION: This treatment algorithm for the intractable facial pain appears to be effective for patients with a wide variety of painful conditions and may be recommended for use in other institutions.

Peripheral neurostimulation for treatment of intractable occipital neuralgia.

OBJECTIVE: Medically intractable pain caused by occipital neuralgia (ON) can be very difficult to control with traditional pain management. Peripheral nerve stimulation (PNS) may serve as a good alternative to destructive surgical manipulations used currently for the treatment of severe ON. METHODS: We analyzed records of 14 consecutive patients (9 women and 5 men; mean age, 43.3 yr) with intractable ON treated with PNS during the period from April 2002 to November 2004. Five patients had unilateral and nine had bilateral PNS electrodes inserted for trial, which was considered successful if patient reported at least 50% decrease of pain on the visual analogue scale. Ten patients proceeded with system internalization, and their long-term results were analyzed. RESULTS: At the time of the last follow-up examination (5-32 mo, mean 22 mo), seven patients (70%) with implanted PNS systems continue to experience beneficial effects of stimulation, including adequate pain control, continuous employment, and decrease in oral pain medications intake. Two patients had their systems explanted because of loss of stimulation effect or significant improvement of pain, and one patient had part of his hardware removed because of infection. CONCLUSION: Overall, the beneficial effect from chronic stimulation in our series persisted in more than half of the patients for whom procedure was considered and in 80% of those who significantly improved during the trial and proceeded with internalization. Thus, chronic PNS may be a safe and relatively effective method for long-term treatment of chronic pain syndrome in patients with medically intractable ON.