Benign Intracranial Hypertension Due to Hypoparathyroidism: A Case Report.

Objective: The objective of this study is to present the rare case of a young girl with idiopathic intracranial hypertension secondary to hypoparathyroidism. Background: Idiopathic intracranial hypertension is a neurological syndrome characterized by elevated intracranial pressure (> 25 cmH2O) in the absence of intracerebral abnormalities or hydrocephalus. The pathophysiology of idiopathic intracranial hypertension is unknown, and rare cases of idiopathic intracranial hypertension secondary to hypoparathyroidism have been described. It is supposed that hypocalcemia causes decrease in the absorption of cerebrospinal fluid in arachnoidal granulations. Methods: The workup of the girl with idiopathic intracranial hypertension and hypoparathyroidism included physical examination, blood tests, diagnostic imaging, and lumbar puncture. Results: We present a 9-year-old female patient who was hospitalized for headache associated with nausea and vomiting for 3 weeks. She underwent an ophthalmologic examination that revealed papilledema. Lumbar puncture revealed an opening pressure of 65 cm H2O; cerebrospinal fluid analysis and brain computed tomography scan were normal. The patient started taking acetazolamide. Blood tests revealed hypocalcemia associated with high phosphorus level and undetectable PTH hormone, which led us to suspect hypoparathyroidism. She had never had cramps, paraesthesias, or tetany. Chvostek's and Trousseau's signs were positive. In the neck ultrasonography, parathyroids were not visible. Oral supplementation with calcitriol and calcium was started. Headache, nausea, and vomiting immediately disappeared after the lumbar puncture, and the papilledema improved gradually. Conclusions: Several anecdotal cases of idiopathic intracranial hypertension secondary to hypoparathyroidism have been described. However, our case report is of particular interest, since the child did not present with typical neurological hypoparathyroidism symptoms. Therefore, we recommend that hypoparathyroidism should be included in diagnostic investigations on children with clinical findings of idiopathic intracranial hypertension, because clinical manifestations of hypoparathyroidism are variable and may involve almost all organ systems.

Homotopic reduction in laser-evoked potential amplitude and laser-pain rating by abdominal acupuncture.

BACKGROUND: The neural mechanism underlying the analgesic effect of acupuncture is largely unknown. We aimed at investigating the effect of abdominal acupuncture (AA) on the laser-evoked potential (LEP) amplitude and laser-pain rating to stimulation of body parts either homotopic or heterotopic to the treated acupoint. METHODS: Laser-evoked potentials were recorded from 13 healthy subjects to stimulation of the right wrist (RW), left wrist (LW) and right foot (RF). LEPs were obtained before, during and after the AA stimulation of an abdominal area corresponding to the representation of the RW. Subjective laser-pain rating was collected after each LEP recording. RESULTS: The amplitude of the N2/P2 LEP component was significantly reduced during AA and 15 min after needle removal to both RW (F = 4.14, p = .02) and LW (F = 5.48, p = .008) stimulation, while the N2/P2 amplitude to RF stimulation (F = 0.94, p = .4) remained unchanged. Laser-pain rating was reduced during AA and 15 min after needle removal only to RW stimulation (F = 5.67, p = .007). CONCLUSION: Our findings showing an AA effect on LEP components to both the ipsilateral and contralateral region homotopic to the treated area, without any LEP change to stimulation of a heterotopic region, suggest that the AA analgesia is mediated by a segmental spinal mechanism. SIGNIFICANCE: Although abdominal acupuncture has demonstrated to be effective in the reduction in laser-evoked potential (LEP) amplitude and laser-pain rating, the exact mechanism of this analgesic effect is not known. In the current study, we found that treatment of an area in the "turtle representation" of the body led to a topographical pattern of LEP amplitude inhibition that can be mediated by a segmental spinal mechanism.

Conditioned pain modulation affects the N2/P2 complex but not the N1 wave: A pilot study with laser-evoked potentials.

BACKGROUND: The 'pain-inhibits-pain' effect stems from neurophysiological mechanisms involving endogenous modulatory systems termed diffuse noxious inhibitory controls (DNIC) or conditioned pain modulation (CPM). Laser-evoked potentials (LEPs) components, the N2/P2 complex, and the N1 wave, reflect the medial and lateral pain pathway, respectively: anatomically, the lateral thalamic nuclei (LT) project mainly to the somatosensory cortex (N1 generator), while the medial thalamic nuclei (MT) are bound to the limbic cortices (N2/P2 generators). METHODS: We applied a CPM protocol in which the test stimulus was laser stimulation and the conditioning stimulus was a cold pressor test. LEPs recordings were obtained from 15 healthy subjects in three different conditions: baseline, during heterotopic noxious conditioning stimulation (HNCS) and post-HNCS. RESULTS: We observed a significant reduction in N2/P2 amplitude during HNCS and a return to pre-test amplitude post-HNCS, whereas the N1 wave remained unchanged during and post-HNCS. CONCLUSIONS: Our results indicate that CPM affects only the medial pain system. The spinothalamic tract (STT) transmits to both the LT and the MT, while the spinoreticulothalamic (SRT) projects only to the MT. The reduction in the amplitude of the N2/P2 complex and the absence of change in the N1 wave suggest that DNIC inhibition on the dorsal horn neurons affects only pain transmission via the SRT, while the neurons that give rise to the STT are not involved. The N1 wave can be a reliable neurophysiological parameter for assessment of STT function in clinical practice, as it does not seem to be influenced by CPM. SIGNIFICANCE: No reports have described the effect of DNIC on lateral and medial pain pathways. We studied the N1 wave and the N2/P2 complex to detect changes during a CPM protocol. We found a reduction in the amplitude of the N2/P2 complex and no change in the N1 wave. This suggests that the DNIC inhibitory effect on dorsal horns neurons affects only pain transmission via the SRT, whereas the neurons that give rise to the STT are not involved.

Acupuncture for Pain in Chronic Pancreatitis: A Single-Blinded Randomized Crossover Trial.

OBJECTIVES: Many patients with painful chronic pancreatitis (CP) have insufficient effect of treatment, and the prevalence of adverse effects is high. Consequently, alternatives to conventional management are needed. We aimed to study the effect of acupuncture in painful CP. METHODS: This was a prospective, single-blinded, randomized crossover trial. Fifteen patients with CP were assigned to a session of acupuncture followed by sham stimulation or vice versa. Patients rated clinical pain scores daily on a 0 to 10 visual analogue scale (VAS) and completed the Patient Global Impression of Change. For mechanistic linkage, resting state electroencephalograms were recorded and quantified by spectral power analysis to explore effects on central pain processing. RESULTS: Acupuncture, compared with sham stimulation, caused more pain relief (2.0 ± 1.5 VAS vs 0.7 ± 0.8 VAS; P = 0.009). The effect, however, was short, and after 1-week follow-up, there was no difference in clinical pain scores between groups (P = 1.0) or the rating of Patient Global Impression of Change (P = 0.8). Electroencephalogram spectral power distributions between sham and acupuncture were comparable between groups (all P > 0.6). CONCLUSIONS: The study presents proof-of-concept for the analgesic effect of acupuncture in pancreatic pain. Although the effect was short lasting, the framework may be used to conceptualize future trials of acupuncture in visceral pain.

Therapeutic approach to pain in neurodegenerative diseases: current evidence and perspectives.

INTRODUCTION: Neurodegenerative diseases are increasing in parallel to the lengthening of survival. The management of Alzheimer's disease (AD) and other dementias, Parkinson's disease (PD) and PD-related disorders, and motor neuron diseases (MND), is mainly targeted to motor and cognitive impairment, with special care for vital functions such as breathing and feeding. Areas covered: The present review focuses on chronic pain in main neurodegenerative diseases, addressing current evidence on pain therapeutic management, pain frequency and clinical features, and possible pathophysiological mechanisms. The search on PubMed had no time limits and was performed by searching for the following key issues: pain, dementia, Alzheimer disease, Parkinson's disease, extrapyramidal disorders, motoneuronal disease, Amyotrophic lateral sclerosis, FXTAS, frequency, pathophysiology, treatments, therapy, efficacy, opioids, side effects. No controlled therapeutic trials and guidelines are currently available. The effects of current therapies such as L-Dopa or riluzole on pain symptoms are not clear. Emerging evidences on the possible anti-nociceptive effects of cannabis or botulinum toxin might be available soon. Expert commentary: Pain needs to be better evaluated and fully considered in the global management of neurodegenerative disease because a more focused treatment may have a positive impact on the global burden of these devastating disorders.

A New Method for Sham-Controlled Acupuncture in Experimental Visceral Pain - a Randomized, Single-Blinded Study.

OBJECTIVE: Acupuncture is increasingly used as an alternative to medical therapy for various pain conditions. To study the effect of acupuncture in experimental and clinical studies, a control condition with sham acupuncture is needed. However, as such models have not been established in assessment of acupunctures effect against visceral pain, this study aimed to validate a new method for blinded sham acupuncture in experimental rectal pain. METHODS: Fifteen subjects underwent a sequence of either sham or real acupuncture in randomized order. In the sham arm, a hollow inner tube with a sharp tip was fitted into an outer tube and subjects were blinded to the stimulations. Before and after the intervention, pain was induced by rectal stimulation with an inflatable balloon distended until the subjects' pain threshold was reached. The resting electroencephalogram (EEG) was quantified by spectral power analysis to explore the central nervous system effects objectively. Additionally, after the second study day, the subject was asked to indicate the sequence of interventions. RESULTS: A significant increase in rectal balloon volume was observed after sham 12 ± 21 mL (P = 0.049) and acupuncture 17 ± 30 mL (P = 0.046). However, the change in volume was not different between groups (P = 0.6). No differences in EEG spectral power distributions between sham and acupuncture were seen (all P > 0.6). The correct sequence of sham and acupuncture was indicated by 36% of the subjects (P = 0.4). CONCLUSIONS: The presented sham procedure provides a valid method for blinding of "sham acupuncture" and may be used in future blinded controlled trials of acupuncture for visceral pain.

Effect of movement on SEPs generated by dorsal column nuclei.

OBJECTIVE: To investigate the effect of the voluntary movement on the amplitude of the somatosensory evoked potentials (SEPs) recorded by an epidural electrode at level of the dorsal column nuclei (DCN). METHODS: Five patients, suffering from chronic pain resistant to pharmacological treatment, underwent an epidural electrode implant at high cervical spinal cord level (C2) for neuromodulation. After tibial nerve stimulation, SEPs were recorded from the epidural electrode contacts, from a Cz lead, and from two electrodes placed over the 12th dorsal vertebra and 4th lumbar vertebra, respectively. SEPs were recorded at rest and during a voluntary flexo-extension movement of the stimulated foot. Beyond the low-frequency SEPs, also the high-frequency oscillations (HFOs), obtained by filtering the recorded traces by means of a 1000-2000 Hz bandpass offline, were analysed. RESULTS: The epidural electrode contacts recorded a triphasic potential (P1-N1-P2), whose negative peak showed a latency similar to that of the P30 far-field response obtained from the scalp. The epidural potential amplitude was significantly decreased by the voluntary movement, as compared to the rest (p<0.01). A main HFO peak, identifiable at around 1200 Hz, was significantly lower in amplitude during movement than at rest (p=0.008). CONCLUSIONS: Our findings suggest that the epidural C2 triphasic wave is a potential arising from DCN. The low-frequency epidural SEP component is subtended by a 1200 Hz HFO, probably generated by post-synaptic events. SIGNIFICANCE: The amplitude reduction of the DCN response during movement is possibly due to decreased excitability of the DCN neurons receiving the somatosensory ascending input.

Familial hypobetalipoproteinemia: early neurological, hematological, and ocular manifestations in two affected twins responding to vitamin supplementation.

Familial hypobetalipoproteinemia is a disorder of lipid metabolism characterized by extremely low plasma levels of apolipoprotein B as well as low levels of total and low-density lipoprotein cholesterol. We report the case of impairment of retinal function and diffuse pain in both legs often related to physical activity, as well as the presence of acanthocytosis on peripheral blood smear. Neurophysiological studies suggested dysfunction of the thin myelinated (A) and unmyelinated (C) fibers, in spite of preserved A fiber function, which has not been previously described in this condition. All clinical symptoms and the neurophysiological abnormalities improved after high-dose vitamin E and A supplementation. These findings suggest that this syndrome may have a wide spectrum of manifestations and an early appearance of symptoms in the pediatric age group.

Learning potentiates neurophysiological and behavioral placebo analgesic responses.

Expectation and conditioning are supposed to be the two main psychological mechanisms for inducing a placebo response. Here, we further investigate the effects of both expectation, which was induced by verbal suggestion alone, and conditioning at the level of N1 and N2-P2 components of CO2 laser-evoked potentials (LEPs) and subjective pain reports. Forty-four healthy volunteers were pseudorandomly assigned to one of three experimental groups: Group 1 was tested with verbal suggestion alone, Group 2 was tested with a conditioning procedure, whereby the intensity of painful stimulation was reduced surreptitiously, so as to make the volunteers believe that the treatment was effective, Group 3 was a control group that allowed us to rule out phenomena of sensitization and/or habituation. Pain perception was assessed according to a Numerical Rating Scale (NRS) ranging from 0=no pain sensation to 10=maximum imaginable pain. Both verbal suggestions (Group 1) and conditioning (Group 2) modified the N2-P2 complex, but not the N1 component of LEPs. However, the suggestion-induced LEP changes occurred without subjective perception of pain decrease. Conversely, the N2-P2 amplitude changes that were induced by the conditioning procedure were associated with the subjective perception of pain reduction. Compared to natural history, conditioning produced more robust reductions of LEP amplitudes than verbal suggestions alone. Overall, these findings indicate that prior positive experience plays a key role in maximizing both behavioral and neurophysiological placebo responses, emphasizing that the placebo effect is a learning phenomenon which affects the early central nociceptive processing.

Spinal cord stimulation normalizes abnormal cortical pain processing in patients with cardiac syndrome X.

Cardiac syndrome X (CSX) is characterized by effort angina, ST-segment depression during stress tests and normal coronary arteries. Abnormal nociception was suggested in these patients by studies showing a reduced cardiac pain threshold; furthermore, we recently found a lack of habituation to pain stimuli using recording of laser evoked potentials (LEPs). In CSX patients with severe angina, spinal cord stimulation (SCS) was shown to improve symptoms. In this study we investigated whether, in these patients, SCS has any effects on the excitability of the nociceptive system, assessed by LEPs recording. We studied 16 CSX patients (61.6+/-7 years; 4 men) who underwent SCS for refractory angina. Cortical LEPs were recorded during stimulation of the chest and right-hand during active SCS (SCS-ON) and in the absence of SCS (SCS-OFF), using a randomized cross-over design. Three sequences of painful stimuli were applied at each site during each test. During the first sequence of chest stimuli, the N2/P2 LEP amplitude was higher during the SCS-ON, compared to the SCS-OFF phase (18.2+/-7.8 vs. 11.5+/-4.4 microV, P=0.006). The N2/P2 amplitude did not change significantly across the three stimulation sequences during the SCS-OFF phase (P=0.22), whereas it decreased progressively during the second and third sequence (to 87.1+/-29.5% and 76.4+/-24.1%, respectively) compared with the first sequence, during the SCS-ON phase (P=0.014). Similar results were observed during right-hand stimulation. Our study shows that in CSX patients SCS is able to restore habituation to peripheral pain stimuli. This effect might contribute to restore the ability of CSX patients to better tolerate cardiac pain.

Effects of transcutaneous electrical nerve stimulation on motor cortex excitability in writer's cramp: neurophysiological and clinical correlations.

We recently reported that transcutaneous electrical nerve stimulation (TENS) applied over forearm flexor muscles, a paradigm producing in physiological conditions transient changes in corticomotoneuronal excitability of forearm muscles, may improve motor symptoms in writer's cramp (WC). In the present study, we explored the possibility that one or repeated sessions of TENS might have beneficial effects on handwriting in WC by remodulating cortical excitability of forearm agonist and antagonist muscles. Motor evoked potentials (MEPs) after transcranial magnetic stimulation of the left motor cortex were recorded from the right flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles, before and after 1 and 15 sessions of TENS applied over flexor muscles in patients and in a control group. One session of TENS induced a significant smaller reduction of MEPs from the FCR and a smaller increase of the MEPs from the ECR in patients than in normal subjects. In WC, repeated sessions of TENS had the effect to decrease MEP amplitude in the FCR and to increase it in the ECR. This modulation was paralleled by a handwriting improvement. In conclusion, repeated TENS sessions may have the effect to re-modulate excitability of the motor cortex in WC and this modulation might partially play a role in temporarily improving the handwriting.

Attentional load of the primary task influences the frontal but not the temporal generators of mismatch negativity.

According to the model hypothesized by Näätänen and Michie, the generation of the mismatch negativity (MMN) requires a mismatch detection, taking place in temporal areas, followed by the activation of frontal generators, underlying attention switching toward the deviant stimulus. We aimed at verifying whether the activation of temporal and frontal regions is dependent on the amount of attentional resources allocable toward the deviant stimulus. We recorded event-related potentials (ERPs) in nine healthy subjects while reading and during a demanding visual task (Multiple Features Target Cancellation, MFTC). Raw data were further evaluated by Brain Electrical Source Analysis (BESA). During the Reading condition, distraction toward the unattended auditory stimuli was reflected by the enhancement of the N1 response to frequent stimuli and by the elicitation of a P3a response to deviant ones. The MMN distribution was explained by bilateral temporal dipoles. During the MFTC condition, no P3a was detected, while source analysis showed the activation of a right frontal generator. Temporal dipoles showed no change between the two conditions: we thus conclude that the earlier mismatch detection is independent on the attentional load. By contrast, the activation of a right frontal subcomponent occurred only during the high-load task, independently on any actual attention shift reflected by the P3a component. We thus discuss the hypothesis whether the right frontal MMN generator, rather than subserving a simple attention switching toward the deviant stimulus, plays a role in modulating the auditory change detection system ("contrast enhancement" model).

Long-lasting modulation of human motor cortex following prolonged transcutaneous electrical nerve stimulation (TENS) of forearm muscles: evidence of reciprocal inhibition and facilitation.

Several lines of evidence indicate that motor cortex excitability can be modulated by manipulation of afferent inputs, like peripheral electrical stimulation. Most studies in humans mainly dealt with the effects of prolonged low-frequency peripheral nerve stimulation on motor cortical excitability, despite its being known from animal studies that high-frequency stimulation can also result in changes of the cortical excitability. To investigate the possible effects of high-frequency peripheral stimulation on motor cortical excitability we recorded motor-evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) of the left motor cortex from the right flexor carpi radialis (FCR), extensor carpi radialis (ECR), and first dorsal interosseous (FDI) in normal subjects, before and after transcutaneous electrical nerve stimulation (TENS) of 30 min duration applied over the FCR. The amplitude of MEPs from the FRC was significantly reduced from 10 to 35 min after TENS while the amplitude of MEPs from ECR was increased. No effects were observed in the FDI muscle. Indices of peripheral nerve (M-wave) and spinal cord excitability (H waves) did not change throughout the experiment. Electrical stimulation of the lateral antebrachial cutaneous nerve has no significant effect on motor cortex excitability. These findings suggest that TENS of forearm muscles can induce transient reciprocal inhibitory and facilitatory changes in corticomotoneuronal excitability of forearm flexor and extensor muscles lasting several minutes. These changes probably may occur at cortical site and seem to be mainly dependent on stimulation of muscle afferents. These findings might eventually lead to practical applications in rehabilitation, especially in those syndromes in which the excitatory and inhibitory balance between agonist and antagonist is severely impaired, such as spasticity and dystonia.

Short-term plastic changes of the human nociceptive system following acute pain induced by capsaicin.

OBJECTIVE: To investigate possible neuroplastic changes induced by pain in cerebral areas devoted to nociceptive input processing. METHODS: CO(2) laser-evoked potentials (LEPs) were recorded from 10 healthy subjects after stimulation of the right and left hand dorsum. Acute pain was obtained by topical application of capsaicin on the skin of right hand dorsum. LEPs were recorded after right and left hand stimulation before capsaicin, at the peak pain and 10-20 min after capsaicin removal. Right hand LEPs were evoked by laser stimuli delivered over the zone of secondary hyperalgesia during capsaicin and on both the zones of primary and secondary hyperalgesia after capsaicin removal. RESULTS: After right hand stimulation, the vertex LEPs, which are generated in the cingulate cortex, were significantly decreased in amplitude during capsaicin application and after capsaicin removal. Moreover, the topography of these potentials was modified after capsaicin removal, shifting from the central toward the parietal region. Dipolar modelling showed that the dipolar source in the anterior cingulate cortex moved backward after capsaicin removal. All these changes were not observed after stimulation of the left hand, contralateral to the application of capsaicin, thus suggesting that functional changes are selective for the painful skin and the adjacent territories. CONCLUSIONS: Our results suggest that acute cutaneous pain may inhibit the neural activity in regions of central nervous system processing nociceptive inputs and cortical representation of these inputs can be rapidly modified in presence of acute pain.