Comparison between deep brain stimulation and magnetic resonance-guided focused ultrasound in the treatment of essential tremor: a systematic review and pooled analysis of functional outcomes.

The current gold standard surgical treatment for medication-resistant essential tremor (ET) is deep brain stimulation (DBS). However, recent advances in technologies have led to the development of incisionless techniques, such as magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy. The authors perform a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement to compare unilateral MRgFUS thalamotomy to unilateral and bilateral DBS in the treatment of ET in terms of tremor severity and quality of life improvement. PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials and SCOPUS databases were searched. 45 eligible articles, published between 1990 and 2019, were retrieved. 1202 patients were treated with DBS and 477 were treated with MRgFUS thalamotomy. Postoperative tremor improvement was greater following DBS than MRgFUS thalamotomy (p<0.001). A subgroup analysis was carried out stratifying by treatment laterality: bilateral DBS was significantly superior to both MRgFUS and unilateral DBS (p<0.001), but no significant difference was recorded between MRgFUS and unilateral DBS (p<0.198). Postoperative quality of life improvement was significantly greater following MRgFUS thalamotomy than DBS (p<0.001). Complications were differently distributed among the two groups (p<0.001). Persistent complications were significantly more common in the MRgFUS group (p=0.042). While bilateral DBS proves superior to unilateral MRgFUS thalamotomy in the treatment of ET, a subgroup analysis suggests that treatment laterality is the most significant determinant of tremor improvement, thus highlighting the importance of future investigations on bilateral staged MRgFUS thalamotomy.

Cerebral mechanisms of hypnotic hypoesthesia. An ERP investigation on the expectancy stage of perception.

The present study aims at identifying reliable markers of neural preparatory processes during hypnosis. To this goal, we recorded the electroencephalographic activity of 23 volunteers regardless of their hypnotizability score. Somatosensory evoked potentials (SEPs) were elicited while participants received non-painful electrical stimuli on the left median nerve in the conditions of relaxation and hypnosis with suggestions of reduced sensation. SEPs analysis was focused on the pre-stimulus activity and revealed two main components: the prefrontal negativity (pN) and the somatosensory negativity (sN) over the frontal and parietal areas of the scalp, respectively. Results showed reduced amplitudes for both components under hypnosis, mostly for the pN, suggesting a change of top-down control of parietal and prefrontal areas. Furthermore, the sLORETA source imaging showed a deactivation of the lateral and anterior portions of the prefrontal cortex (PFC) during the hypnotic state. The present study highlights the downregulation of the PFC as a core aspect of the adopted hypnotic task and confirms the ability of hypnosis to modulate the activity of frontal executive functions. Further, since the majority of participants fell into the medium range of hypnotizability, the present findings could reflect the hypnosis effects in most of the population.

Second-order spinal cord pathway contributes to cortical responses after long recoveries from dorsal column injury in squirrel monkeys.

Months after the occurrence of spinal cord dorsal column lesions (DCLs) at the cervical level, neural responses in the hand representation of somatosensory area 3b hand cortex recover, along with hand use. To examine whether the second-order spinal cord pathway contributes to this functional recovery, we injected cholera toxin subunit B (CTB) into the hand representation in the cuneate nucleus (Cu) to label the spinal cord neurons, and related results to cortical reactivation in four squirrel monkeys (Saimiri boliviensis) at least 7 months after DCL. In two monkeys with complete DCLs, few CTB-labeled neurons were present below the lesion, and few neurons in the affected hand region in area 3b responded to touch on the hand. In two other cases with large but incomplete DCLs, CTB-labeled neurons were abundant below the lesion, and the area 3b hand cortex responded well to tactile stimulation in a roughly somatotopic organization. The proportions of labeled neurons in the spinal cord hand region reflected the extent of cortical reactivation to the hand. Comparing monkeys with short and long recovery times suggests that the numbers of labeled neurons below the lesion increase with time following incomplete DCLs (<95%) but decrease with time after nearly complete DCLs (≥95%). Taken together, these results suggest that the second-order spinal cord pathway facilitates cortical reactivation, likely through the potentiation of persisting tactile inputs from the hand to the Cu over months of postlesion recovery.

Impaired Corneal Sensation and Nerve Loss in a Type 2 Rat Model of Chronic Diabetes Is Reversible With Combination Therapy of Menhaden Oil, α-Lipoic Acid, and Enalapril.

PURPOSE: This study investigated the efficacy of monotherapy versus combination of menhaden oil, α-lipoic acid, and enalapril on corneal sensation and morphometry and other neuropathy-related endpoints in a rat model of type 2 diabetes. METHODS: Male Sprague-Dawley rats (aged 12 weeks) were fed a high-fat diet for 8 weeks followed by 30 mg/kg streptozotocin. After 16 weeks of hyperglycemia, 12-week treatments consisting of menhaden oil, α-lipoic acid, enalapril, or their combination were initiated. Before and after treatments, we performed analyses of multiple neural and vascular endpoints including corneal sensitivity, corneal nerve density, vascular reactivity of epineurial arterioles, motor and sensory nerve conduction velocity, intraepidermal nerve fiber density, and thermal nociception. RESULTS: Before treatment, all the neural and vascular endpoints in diabetic rats were impaired. Treating diabetic rats with monotherapy was effective in improving neural and vascular deficits with menhaden oil being most efficacious. However, the combination therapy provided the greatest benefit and improved/reversed all nerve and vascular deficits. The effect of combination therapy on corneal relative sensitivity and structure (in mm/mm), primary endpoints for this study, for control, diabetic, and diabetic treated rats was 4.2 ± 1.4 and 7.5 ± 0.5, 12.1 ± 1.3* and 3.8 ± 0.2*, and 6.6 ± 2.3 and 7.3 ± 0.5, respectively (*P < 0.05 compared with control rats; P < 0.05 compared with diabetic rats). CONCLUSIONS: These studies suggest that a combination therapeutic approach may be most effective for treating vascular and neural complications of type 2 diabetes.

Minimally symptomatic hypocalcaemia unmasking celiac disease.

INTRODUCTION: Celiac disease is an autoimmune disease of the small intestine which occurs in genetically predisposed people of all ages. A large clinical spectrum of manifestations accompanies the onset of the disease with diarrhoea, flatulence and weight loss being the most common. However, findings like osteoporosis, iron deficiency, anaemia and hypocalcaemia could also insinuate the existence of the disease. CASE PRESENTATION: We report the case of a 55-year-old man with numbness and tingling of the upper extremities due to hypocalcaemia that proved to be an uncommon case of celiac disease. CONCLUSION: A non-negligible number of adult patients with celiac disease can present with only minor and subclinical manifestations of the disease. As such, hypocalcaemia may be the sole manifestation of celiac disease. A high index of suspicion is needed for prompt diagnosis.

Osteopathic manipulative treatment for facial numbness and pain after whiplash injury.

Whiplash injury is often caused by rear-end motor vehicle collisions. Symptoms such as neck pain and stiffness or arm pain or numbness are common with whiplash injury. The author reports a case of right facial numbness and right cheek pain after a whiplash injury. Osteopathic manipulative treatment techniques applied at the level of the cervical spine, suboccipital region, and cranial region alleviated the patient's facial symptoms by treating the right-sided strain of the trigeminal nerve. The strain on the trigeminal nerve likely occurred at the upper cervical spine, at the nerve's cauda, and at the brainstem, the nerve's point of origin. The temporal portion of the cranium played a major role in the strain on the maxillary.

An investigation into the hypoalgesic effects of transcutaneous piezoelectric current on experimentally induced thermal stimuli in healthy participants.

OBJECTIVES: To investigate the effects of transcutaneous piezoelectric currents on experimentally induced thermal pain in healthy human participants. MATERIALS AND METHODS: A repeated measure cross-over study recorded sensory detection and pain thresholds to contact thermal stimuli during active and placebo (no current) transcutaneous piezoelectric current in 15 pain-free healthy human volunteers. Active transcutaneous piezoelectric current (6 µA) was delivered as 35 high voltage single rectangular pulses (1 Hz) at the LI4 (Hegu) acupuncture point. RESULTS: Repeated measures ANOVA found that active and placebo transcutaneous piezoelectric current elevated thresholds for warm sensation, heat pain, and cold sensation. However, there were no statistically significant effects for active piezoelectric current compared with placebo for any outcome measure. CONCLUSIONS: Reductions in experimentally induced pain were not due to piezoelectric currents per se. These findings challenge claims about the efficacy of transcutaneous piezoelectric currents for pain relief. A clinical trial is needed.

Efficacy of keishibukuryogan, a traditional Japanese herbal medicine, in treating cold sensation and numbness after stroke: clinical improvement and skin temperature normalization in 22 stroke patients.

Cold sensation and numbness have been reported as post-stroke sensory sequelae attributable to distal axonopathy, which is caused by chronic ischemia of diseased limbs resulting from dysfunction of vasomotor regulatory systems. Keishibukuryogan is a traditional herbal medicine used to treat symptoms of peripheral ischemia such as cold extremities. This study investigated clinical improvement and skin temperature in peripheral ischemia patients to determine the efficacy of keishibukuryogan in alleviating post-stroke cold sensation and numbness. Twenty-two stroke patients with cold sensation and/or numbness were enrolled in this study. Subjective cold sensation and numbness, evaluated using the visual analogue scale, were found in 21 and 31 limbs, respectively. The skin temperature of diseased and healthy limbs was recorded. We observed all patients for 4 weeks and 17 patients for 8 weeks after administration of keishibukuryogan. The skin temperature of diseased limbs was significantly higher than baseline at 4 weeks and 8 weeks, whereas that of healthy limbs did not change significantly. Cold sensation and numbness were significantly improved at 4 weeks and 8 weeks compared to baseline. Keishibukuryogan administration resulted in warming of diseased limbs and improved cold sensation and numbness, probably by increasing peripheral blood flow.

[Observation on therapeutic effect of digital acupoint pressure for treatment of the nerve root type of cervical spondylosis].

OBJECTIVE: To observe the therapeutic effect of digital acupoint pressure for treatment of the nerve root type of cervical spondylosis. METHODS: Four hundred cases were randomly divided into a digital acupoint pressure group (DAP group) and a medicine group, 200 cases in each group. Acupoints of Quepen (ST 12), Jianjing (GB 21) and Tianzong (ST 11) etc. were used for digital pressing in the DAP group; and Chinese herb medicine of Gentongping was routinely taken in the medicine group. After three treatment courses, the symptoms of pain and numbness, the signs of pressure measurement by compression of head, brachial plexus drawer test and arm myodynamia, as well as the total cumulative scores of daily living capability, were compared. RESULTS: After treatment, the total cumulative scores of numbness, pressure measurement by compression of head, brachial plexus drawer test, arm myodynamia and daily living capability in both groups were obviously better than those of before treatment (all P<0.01); but there was a significant difference on the total cumulative score of the symptoms and signs between the two groups. The cured rate of 78.0% and total effective rate of 99.0% in the DAP group were better than those of 61.0% and 87.0% in the medicine group, respectively (both P<0.01). CONCLUSION: Digital acupoint pressure plays an active role in improving the symptoms and signs on patients with nerve root type of cervical spondylosis, which is better than Chinese herb medicine of Gentongping.

Peripheral neuropathy in rats exposed to dichloroacetate.

The use of dichloroacetate (DCA) for treating patients with mitochondrial diseases is limited by the induction of peripheral neuropathy. The mechanisms of DCA-induced neuropathy are not known. Oral DCA treatment (50-500 mg/kg per day for up to 16 weeks) induced tactile allodynia in both juvenile and adult rats; concurrent thermal hypoalgesia developed at higher doses. Both juvenile and adult rats treated with DCA developed nerve conduction slowing that was more pronounced in adult rats. No overt axonal or glial cell abnormalities were identified in peripheral nerves or spinal cord of any DCA-treated rat, but morphometric analysis identified a reduction of mean axonal caliber of peripheral nerve myelinated fibers. Dichloroacetate treatment also caused accumulation of oxidative stress markers in the nerves. These data indicate that behavioral, functional, and structural indices of peripheral neuropathy may be induced in both juvenile and adult rats treated with DCA at doses similar to those in clinical use. Dichloroacetate-induced peripheral neuropathy primarily afflicts axons and involves both metabolic and structural disorders. The DCA-treated rat may provide insight into the pathogenesis of this peripheral neuropathy and facilitate development of adjuvant therapeutics to prevent this disorder that currently restricts the clinical use of DCA.

Evaluation of transcutaneous electrical simulation to improve recovery from corneal hypoesthesia after LASIK.

PURPOSE: To evaluate the efficacy, and safety of transcutaneous electrical stimulation (TES) to accelerate corneal nerve regeneration and improved recovery from corneal hypesthasia after laser-assisted in situ keratomileusis (LASIK). SETTING: Khodadoust Eye Hospital, Shiraz, Fars, Iran METHODS: This prospective, randomized, clinical study comprised 40 eyes of 20 patients scheduled to undergo bilateral LASIK. In each patient, one eye was randomly assigned to receive transcutaneous electrical stimulation (20 HZ) for 60 minutes, and the other eye allocated as control. Corneal sensitivity was measured using the Cochet-Bonnet esthesiometer in four areas outside and five areas inside the LASIK flap preoperatively, and at 1 day, 1 week, 1 month, and 3 months postoperatively. Best-corrected visual acuity and the incidence of adverse events were noted at each visit. RESULTS: For all four points outside the LASIK flap, normal corneal sensitivity was maintained throughout the study; no significant difference was found between the study eyes and the control eyes at these points (P > 0.05). All points within the LASIK flap except the point closest to the hinge demonstrated profound corneal hypoesthesia at 1 day, 1 week, and 1 month postoperatively, with no differences noted between the control and study eyes (P > 0.05). After 3 months, points within the flap had statistically significantly better corneal sensitivity in the study group than in the control group (P < 0.05). CONCLUSIONS: Transcutaneous electrical stimulation significantly improves corneal sensitivity at 3 months after LASIK. This may be due to accelerated corneal nerve regeneration by electrical stimulation.

The impact of muscular variation on the neurodynamic test for the median nerve in a healthy population with Langer's axillary arch.

OBJECTIVE: The neurodynamic test of the median nerve (ULNT1) is frequently used to assess the mechanics and physiology of the brachial plexus and median nerve. The present study looks for a positive ULNT1 in a healthy population with Langer's axillary arch (LAA) and analyzes whether LAA affects the elbow extension range of motion (EE-ROM) of the ULNT1. METHOD: Of 640 volunteers screened, 26 LAA sides were finally included. Additional history taking revealed "minor symptoms" in some subjects. Minor symptoms do not qualify as a disorder because there is no interference with daily activities and no medical advice is sought. This study investigates whether the ULNT1 can (re)produce minor symptoms or abnormal responses in subjects with LAA. The EE-ROM was compared between the subjects' left and right side, and the subtraction angle-which is the effect of placing the cervical spine in contralateral lateral flexion-was compared between LAA sides and controls. RESULTS: Langer's axillary arch sides showed a significant increase in the occurrence of minor symptoms and positive ULNT1, but no influence was observed on the EE-ROM. CONCLUSIONS: These findings suggest that LAA may be capable of transiently provoking the axillary neurovascular bundle. The unaffected EE-ROM may be the consequence of a vascular origin of the minor symptoms or the consequence of an ulnar nerve/medial cord response to the ULNT1.

Diminished plantar cutaneous sensation and postural control.

The purpose of this study was to assess the effect of diminished plantar cutaneous sensation induced by cooling on postural control during double- and single-limb quiet standing. 32 healthy adults were tested on an intervention day and control day. The intervention consisted of 10 min. of ice immersion of the plantar aspect of the feet prior to balance testing. Dependent variables were center of pressure velocity and area during double- and single-limb stance with eyes open and closed. Significant interactions were found between sensation and vision for double-limb center of pressure area, with a significant reduction in area of center of pressure excursions after reducing sensation with eyes closed but not with eyes open. The area of center of pressure excursions may have been reduced in an effort to curtail exploratory postural behavior given the altered afferent input from plantar receptors. There were no significant differences for plantar hypoesthesia in single-limb stance.

Double dissociation between representational personal and extrapersonal neglect.

BACKGROUND: Although perceptual and representational neglect are frequently associated, the demonstration of a double dissociation between both neglect forms suggests that both rely on different central mechanisms. In addition, perceptual neglect can be selectively observed within personal space or extrapersonal space. However, it is not known whether the latter dissociation also exists in representational neglect. METHODS: The authors investigated this question in two brain-damaged patients with anatomically different lesions sites, using neuropsychological tests specifically designed to assess perceptual and representational neglect in both personal and extrapersonal space. RESULTS: Patients presented a double dissociation with respect to personal and extrapersonal space in representational neglect. CONCLUSIONS: These data suggest that the cerebral networks that process mental space representation use similar principles of space compartmentalization as those used by cerebral networks processing perceived space.

Sensory changes in the forehead of patients with complex regional pain syndrome.

The aim of this study was to investigate involvement of central mechanisms in complex regional pain syndrome (CRPS). In particular, we wished to determine whether hyperalgesia extends ipsilaterally from the affected limb to the forehead. The heat-pain threshold, pressure-pain threshold, and ratings of cold and sharpness were investigated on each side of the forehead and in the affected and unaffected limbs of 38 patients with features of CRPS. In addition, touch thresholds were investigated in the limbs. The pressure-pain threshold was lower on the ipsilateral forehead than contralaterally, consistent with the presence of static mechanical hyperalgesia. Although the heat-pain threshold and ratings of sharpness and cold did not differ between the two sides of the forehead in the group as a whole, the sharpness of pinprick sensations in the affected limb was mirrored by similar sensations in the ipsilateral forehead. Conversely, diminished sensitivity to light touch in the affected limb was associated with diminished sensitivity to sharpness, cold and heat-pain in the ipsilateral forehead. These findings suggest that central nociceptive processing is disrupted in CRPS, possibly due to disturbances in the thalamus or higher cortical centres.

Sensory re-education after nerve repair: aspects of timing.

The recovery of functional sensibility after nerve transection and repair is often disappointing. Here we address the timing of sensory re-education that aims at re-learning and modulating the changed sensory code from the hand after such an injury. Such training utilises the capacity for cortical functional re-modelling which characterises the young as well as the adult brain. Sensory re-education is traditionally not introduced until there is reinnervation in the hand, and such a late onset of training may be one explanatory factor for the poor functional results after nerve repair. Since functional reorganisation changes of the cortex occurring after changes in peripheral input are very fast processes, we suggest that this specific intervention should be introduced very early in the rehabilitation phase--already in the initial phase after nerve repair when no axons have yet arrived to the asensible hand. The goal is to avoid, minimise and modulate the central functional re-organisation which follows the de-afferentiation associated with nerve injury and repair. This early intervention can be done with the use of artificial sensibility the first post-operative day. According to this technique, based on sense substitution and utilising the multimodal capacity of the brain, miniature microphones on the fingertips of the asensible hand pick up the friction sound generated by active touch. The vibro-tactile signals are stereophonically transposed to vibro-acoustic signals, thereby providing an alternate feed-back which hypothetically helps to maintain or re-establish the cortical hand map.

Conversion disorder mimicking Dejerine-Roussy syndrome (thalamic stroke) after spinal cord stimulation.

OBJECTIVE: Dejerine-Roussy syndrome is a complex of various signs and symptoms in patients suffering from central thalamic pain, usually secondary to a vascular etiology. We describe a patient presenting with the potentially devastating signs and symptoms of thalamic stroke, at least temporally related to spinal cord stimulator implantation. The etiology of the patient's affliction was subsequently revealed to be a conversion disorder. Case report A 37-year-old woman presented for spinal cord stimulation as treatment of her brachial plexopathy after failure of conservative therapy. Before implantation, she underwent a clinical interview with a psychologist and psychometric testing. No psychological pathology was detected. Trial and permanent implantation of the cervical stimulator lead and pulse generator were uneventful. Eleven days after receiving the permanent implant, the patient experienced right-sided hemicorporal numbness and burning dysesthesia. The patient was admitted, and a diagnosis of Dejerine-Roussy syndrome (thalamic stroke) was made. She was discharged, and her symptomatology waxed and waned over a period of weeks. The patient was subsequently admitted for psychiatric evaluation because of anxiety attacks. During her protracted admission, her psychiatrists strongly suspected a conversion disorder. The stimulator was removed, and the patient received supportive care only. Within 6 months, sensory symptoms and all motor deficits had completely resolved. CONCLUSIONS: Despite careful preoperative evaluation, latent psychosocial issues may limit the effectiveness of spinal cord stimulation. We present a case of conversion disorder masquerading as Dejerine-Roussy syndrome after spinal cord stimulation. The implications of the failure of preoperative psychological evaluation and screening to avert implantation are discussed.

Altered central somatosensory processing in chronic pain patients with "hysterical" anesthesia.

OBJECTIVE: The authors hypothesized that central factors may underlie sensory deficits in patients with nondermatomal somatosensory deficits (NDSD) and that functional brain imaging would reveal altered responses in supraspinal nuclei. BACKGROUND: Patients with chronic pain frequently present with NDSD, ranging from hypoesthesia to complete anesthesia in the absence of substantial pathology and often in association with motor weakness and occasional paralysis. Patients with pain and such pseudoneurologic symptoms can be classified as having both a pain disorder and a conversion disorder (Diagnostic and Statistical Manual of Mental Disorders-IV classification). METHODS: The authors tested their hypothesis with functional MRI (fMRI) of brush and noxious stimulation-evoked brain responses in four patients with chronic pain and NDSD. RESULTS: The fMRI findings revealed altered somatosensory-evoked responses in specific forebrain areas. Unperceived stimuli failed to activate areas that were activated with perceived touch and pain: notably, the thalamus, posterior region of the anterior cingulate cortex (ACC), and Brodmann area 44/45. Furthermore, unperceived stimuli were associated with deactivations in primary and secondary somatosensory cortex (S1, S2), posterior parietal cortex, and prefrontal cortex. Finally, unperceived (but not perceived) stimuli activated the rostral ACC. CONCLUSIONS: Diminished perception of innocuous and noxious stimuli is associated with altered activity in many parts of the somatosensory pathway or other supraspinal areas. The cortical findings indicate a neurobiological component for at least part of the symptoms in patients presenting with nondermatomal somatosensory deficits.