Effects of the TENS device, Exopulse Mollii Suit, on pain related to fibromyalgia: An open-label study.

Fibromyalgia is characterized by diffuse and chronic pain, that is often only partially alleviated by the available pharmacological treatments. Therefore, nonpharmacological interventions such as transcutaneous electrical stimulation (TENS) are highly needed to improve the quality of life of this population. However, the classical TENS devices offer a limited number of electrodes and are not adapted to this diffuse painful condition. For these reasons, we aimed to assess the effects of a new TENS device, the Exopulse Mollii Suit, that can stimulate up to 40 muscle groups integrated into pants and jackets and connected to a control unit. We report the data of 50 patients who received one session of active stimulation (pulse intensity 2 mA, and pulse frequency 20 Hz). Pain intensity was evaluated by means of the visual analogue scale (VAS), before (T0) and after the session (T1), and 24 h later (T24). Compared to baseline scores, a significant decrease in VAS was observed after the session (p<0.001), and 24 h later (p<0.001). T1 scores were significantly lower than T24 scores (p<0.001). Therefore, this new system seems to exert analgesic effects whose mechanisms primarily evoke the theory of "gate control". The effects were transient and started to decrease the following day, highlighting the need for additional studies to better evaluate the long-term effects of this intervention on pain, mood, and quality of life.

Autoimmune Brainstem Encephalitis: An Illustrative Case and a Review of the Literature.

Autoimmune brainstem encephalitis (BSE) is a rare neurological condition with a wide range of underlying etiologies. It can be subdivided into two broad groups: a primary inflammatory disease of the central nervous system (CNS) or a brainstem disorder secondary to systemic diseases where the CNS is only one of many affected organs. Symptoms range from mild to life-threatening manifestations. Most cases respond well to immunotherapy. Therefore, broad and in-depth knowledge of the various inflammatory disorders that target the brainstem is essential for guiding the diagnostic approach and assisting in early initiation of appropriate therapy. We herein report on a case of BSE and provide an overview of the various causes of autoimmune BSE with an emphasis on the clinical manifestations and diagnostic approach.

The value of sensory nerve conduction studies in the diagnosis of Guillain-Barré syndrome.

Electrophysiology plays a determinant role in Guillain-Barré syndrome (GBS) diagnosis, classification, and prognostication. However, traditional electrodiagnostic (EDX) criteria for GBS rely on motor nerve conduction studies (NCS) and are suboptimal early in the course of the disease or in the setting of GBS variants. Sensory nerve conduction studies, including the sural-sparing pattern and the sensory ratio are not yet included in EDX criteria despite their well-established role in GBS diagnosis. The aim of this review is to discuss the diagnostic value of sensory NCS in GBS, their role in establishing the diagnosis and predicting the outcome according to the various subtypes of the disease.

Tremor in Multiple Sclerosis-An Overview and Future Perspectives.

Tremor is an important and common symptom in patients with multiple sclerosis (MS). It constituted one of the three core features of MS triad described by Charcot in the last century. Tremor could have a drastic impact on patients' quality of life. This paper provides an overview of tremor in MS and future perspectives with a particular emphasis on its epidemiology (prevalence: 25-58%), clinical characteristics (i.e., large amplitude 2.5-7 Hz predominantly postural or intention tremor vs. exaggerated physiological tremor vs. pseudo-rhythmic activity arising from cerebellar dysfunction vs. psychogenic tremor), pathophysiological mechanisms (potential implication of cerebellum, cerebello-thalamo-cortical pathways, basal ganglia, and brainstem), assessment modalities (e.g., tremor rating scales, Stewart-Holmes maneuver, visual tracking, digitized spirography and accelerometric techniques, accelerometry-electromyography coupling), and therapeutic options (i.e., including pharmacological agents, botulinum toxin A injections; deep brain stimulation or thalamotomy reserved for severe, disabling, or pharmaco-resistant tremors). Some suggestions are provided to help overcome the unmet needs and guide future therapeutic and diagnostic studies in this complex disorder.

Paroxysmal Symptoms in Multiple Sclerosis-A Review of the Literature.

Paroxysmal symptoms are well-recognized manifestations of multiple sclerosis (MS). These are characterized by multiple, brief, sudden onset, and stereotyped episodes. They manifest as motor, sensory, visual, brainstem, and autonomic symptoms. When occurring in the setting of an established MS, the diagnosis is relatively straightforward. Conversely, the diagnosis is significantly more challenging when they occur as the initial manifestation of MS. The aim of this review is to summarize the various forms of paroxysmal symptoms reported in MS, with emphasis on the clinical features, radiological findings and treatment options.

Transcranial Direct Current Stimulation of the Occipital Cortex in Medication Overuse Headache: A Pilot Randomized Controlled Cross-Over Study.

BACKGROUND: Medication overuse headache (MOH) is a chronic pain syndrome that arises from the frequent use of acute antimigraine drugs. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique with a possible therapeutic effect in this particular context. METHODS: This was a randomized, sham-controlled, cross-over study. Eighteen patients with MOH (17 women, age range: 20-38 years) received three sets of three consecutive daily sessions of tDCS: anodal tDCS over the prefrontal cortex, cathodal tDCS over the occipital cortex ipsilateral to the dominant side of migraine pain, and sham. The order in which the tDCS blocks were delivered was randomly defined based on a 1:1:1 ratio. Patients filled in a migraine diary that allowed recording of the pain intensity (visual analogue scale) and the daily consumption of analgesic pills from one week before to two weeks after each condition. RESULTS: Both prefrontal and occipital tDCS lowered the total number of migraine days and the number of severe migraine days per week at week 1, but only the effects of occipital tDCS on these two outcomes lasted until week 2. Only occipital tDCS decreased the daily analgesic pills consumption, at weeks 1 and 2. CONCLUSION: Three consecutive days of cathodal occipital tDCS appear to improve the clinical outcomes in patients with MOH.

Effects of Transcranial Direct Current Stimulation on Hand Dexterity in Multiple Sclerosis: A Design for a Randomized Controlled Trial.

BACKGROUND: Cerebellar and motor tracts are frequently impaired in multiple sclerosis (MS). Altered hand dexterity constitutes a challenge in clinical practice, since medical treatment shows very limited benefits in this domain. Cerebellar control is made via several cerebellocortical pathways, of which the most studied one links the cerebellum to the contralateral motor cortex via the contralateral ventro-intermediate nucleus of the thalamus influencing the corticospinal outputs. Modulating the activity of the cerebellum or of the motor cortex could be of help. METHOD: The main interest here is to evaluate the efficacy of transcranial direct current stimulation (tDCS), a noninvasive brain stimulation technique, in treating altered dexterity in MS. Forty-eight patients will be recruited in a randomized, double-blind, sham-controlled, and crossover study. They will randomly undergo one of the three interventions: anodal tDCS over the primary motor area, cathodal tDCS over the cerebellum, or sham. Each block consists of five consecutive daily sessions with direct current (2 mA), lasting 20 min each. The primary outcome will be the improvement in manual dexterity according to the change in the time required to complete the nine-hole pegboard task. Secondary outcomes will include fatigue, pain, spasticity, and mood. Patients' safety and satisfaction will be rated. DISCUSSION: Due to its cost-effective, safe, and easy-to-use profile, motor or cerebellar tDCS may constitute a potential tool that might improve dexterity in MS patients and therefore ameliorate their quality of life.

Precise finger somatotopy revealed by focal motor cortex injury.

BACKGROUND: Somatotopy is considered the hallmark of the primary motor cortex. While this is fundamentally true for the major body parts (head, upper and lower extremities), evidence supporting the existence of within-limb somatotopy is scarce. METHOD: We report a young man presenting recurrent ischemic strokes with selective finger weakness in whom serial motor cortex mapping procedures were performed. RESULT: Following the first stroke, which largely spared the motor cortex, motor mapping displayed overlap of the motor representations of the hand muscles. The second focal stroke, affecting the lateral part of the hand knob, resulted in selective loss of the first dorsal interosseous muscle motor evoked potentials while sparing those of the adductor digiti minimi muscle. This observation is in apparent contradiction with the first mapping results that suggested complete overlap of motor representations. DISCUSSION: Our mapping results provide evidence for the existence of very precise within-limb somatotopy and confirm the proposed homuncular order, whereby lateral fingers are represented laterally and medial fingers medially. The discrepancy between the initial and subsequent mapping results is discussed in light of functional organization of the primary motor cortex.

Vitamin K2 Status and Arterial Stiffness Among Untreated Migraine Patients: A Case-Control Study.

OBJECTIVE: We aimed to examine arterial stiffness and vitamin K2 status in migraine subjects by comparison to controls. BACKGROUND: Migraine is a primary headache disorder that has been associated with an increased risk of cardiovascular events. Mechanisms underlying this increased risk, however, remain unclear. Vitamin K2 deficiency emerged as a cardiovascular risk factor, but vitamin K2 status has never been explored in migraine subjects. DESIGN AND METHODS: This is a case-control, single-center, observational study that includes a cohort of subjects with migraine and their age- and sex-matched controls. Arterial stiffness was measured using carotid-femoral pulse wave velocity (cfPWV). Dephosphorylated-uncarboxylated matrix-Gla-protein (dp-ucMGP) was used as a marker for vitamin K2 status. A propensity-matched scoring method was used. RESULTS: A total of 146 patients (73 matched pairs) were included in this study, of whom 89% were women with a mean age of 31.9 ± 8.4 years. Compared with controls, migraine patients had statistically significantly higher mean cfPWV (7.2 ± 1.1 vs 6.4 ± 0.8 m/s, 95% confidence interval (CI) of mean difference [0.45, 1.08], P < .001), as well as higher dp-ucMGP (454.3 ± 116.7 pmol/L vs 379.8 ± 126.6 pmol/L, 95% CI of mean difference [34.63, 114.31], P < .001). Higher cfPWV was associated with higher dp-ucMGP concentrations only in the migraine with aura (MWA) group. Moreover, migraine subjects had a higher frequency of vitamin K2 deficiency (dp-ucMGP ≥ 500 pmol/L) compared to controls, but this association was not statistically significant (23/73 [31.5%] vs 16/73 [21.9%], P = .193). CONCLUSIONS: Individuals with migraine have worse indices of arterial stiffness as compared with their age- and sex-matched control subjects. This increase in arterial stiffness is associated with an increase in markers of vitamin K2 deficiency in the MWA group.

Cortical Excitability Measures May Predict Clinical Response to Fampridine in Patients with Multiple Sclerosis and Gait Impairment.

Background: Most multiple sclerosis (MS) patients will develop walking limitations during the disease. Sustained-release oral fampridine is the only approved drug that will improve gait in a subset of MS patients. Objectives: (1) Evaluate fampridine cortical excitability effect in MS patients with gait disability. (2) Investigate whether cortical excitability changes can predict the therapeutic response to fampridine. Method: This prospective observational study enrolled 20 adult patients with MS and gait impairment planned to receive fampridine 10 mg twice daily for two consecutive weeks. Exclusion criteria included: Recent relapse (<3 months), modification of disease modifying drugs (<6 months), or Expanded Disability Status Scale (EDSS) score >7. Neurological examination, timed 25-foot walk test (T25wt), EDSS, and cortical excitability studies were performed upon inclusion and 14 days after initiation of fampridine. Results: After treatment, the mean improvement of T25wt (ΔT25wt) was 4.9 s. Significant enhancement of intra-cortical facilitation was observed (139% versus 241%, p = 0.01) following treatment. A positive correlation was found between baseline resting motor threshold (rMT) and both EDSS (r = 0.57; p < 0.01) and ΔT25wt (r = 0.57, p = 0.01). rMT above 52% of the maximal stimulator output was found to be a good predictor of a favorable response to fampridine (accuracy: 75%). Discussion: Fampridine was found to have a significant modulatory effect on the cerebral cortex, demonstrated by an increase in excitatory intracortical processes as unveiled by paired-pulse transcranial magnetic stimulation. rMT could be useful in selecting patients likely to experience a favorable response to fampridine.

Cathodal Transcranial Direct Current Stimulation of the Occipital cortex in Episodic Migraine: A Randomized Sham-Controlled Crossover Study.

Three consecutive daily sessions of cathodal transcranial direct current stimulation (tDCS) was sufficient to show a significant decrease in headache duration and intensity as well as tablets consumption, in patients suffering from episodic migraine. BACKGROUND: Migraine prophylaxis is recommended in patients with frequent and/or intense headaches, but poor tolerability and lack of efficacy of preventive drugs are common in clinical practice. Hence, new prophylactic strategies are needed. OBJECTIVE: The aim of this study was to evaluate the efficacy of tDCS in terms of migraine prophylaxis. METHODS: This was a double blind and sham-controlled trial. Forty-two migraine patients were randomly assigned in a crossover design to receive three consecutive daily sessions of both sham and cathodal tDCS stimulation (2.0 mA, 20 min) over the occipital cortex of the dominant side of the migraine pain (O1/O2). Migraine duration and intensity, number of analgesic tablets, and number of headache-free days (where no headache abortive medications are taken) were recorded one week before and two weeks after treatment. A washout period of one week was allowed before crossing to the other treatment arm. RESULTS: Relative to sham, cathodal stimulation was associated with a significant reduction in the number of headache days, tablets consumption, and pain intensity; and a significant increase in the number of headache-free days. These beneficial effects were sustained over two weeks. No serious side effects were observed, and the procedure was well tolerated. CONCLUSION: Based on these findings, cathodal tDCS applied to the occipital cortex seems to be an effective and well tolerated alternative to pharmacotherapy in patients with episodic migraine.

Posterior reversible encephalopathy syndrome (PRES) in mesenteric leiomyosarcoma: A case report.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a syndrome characterized by headache, confusion, visual loss and seizures. Many factors influence the appearance of this syndrome, predominantly eclampsia, certain medical treatments and malignant hypertension. Diagnosed by typical transient lesions on magnetic resonance imaging. CASE REPORT: We present a case of mesenteric leiomyosarcoma in a 52 year old woman, who had severe headache, abdominal heaviness, and hypertension. Investigations revealed a mesenteric mass and a Posterior Reversible Encephalopathy Syndrome features on brain MRI, suggesting renin secretion by the tumor, causing the patient's symptoms. CONCLUSION: Patient's symptoms disappeared after resection of the tumor, suggesting a renin production cessation.

The ulnar ratio as a sensitive and specific marker of acute inflammatory demyelinating polyneuropathy.

OBJECTIVES: To explore the value of a novel sensory criterion, the ulnar ratio - defined as the SNAP amplitude of the palmar cutaneous (pUN) over that of the dorsal branch (dUN) of the ulnar nerve - as a predictor of Acute Inflammatory Demyelinating Polyneuropathy (AIDP). METHODS: We prospectively included 22 patients with AIDP, 20 patients with diabetic peripheral neuropathy (DPN), and 18 controls. Eligible subjects underwent nerve conduction studies including, among others, the dUN, pUN, and sural nerve. RESULTS: A sural sparing pattern was found in 72% of AIDP cases. The ulnar ratio was significantly lower in patients with AIDP compared to those with DPN or controls. The ROC curve area to discriminate AIDP (versus controls and diabetics together) was higher with the ulnar ratio and pUN compared to dUN. An ulnar ratio ≥ 0.78 seems to be the best threshold to rule out the diagnosis of AIDP, with a specificity of 100% and a sensitivity of 87%. The ulnar ratio was equally reliable in the subgroup of patients presenting within a week of symptoms onset. CONCLUSION: The ulnar ratio is a highly sensitive and specific marker of AIDP and can help confirm the diagnosis when direct signs of demyelination are lacking. SIGNIFICANCE: Incorporating specific sensory abnormalities, such as the ulnar ratio, in the electrodiagnostic criteria of AIDP could enhance their reliability.

Hyperacoustic hypoacusis: A new pontine syndrome-Case report.

We herein report a unique case of a lateral pontine demyelinating lesion presenting with unilateral sensorineural hearing loss and paradoxical ipsilateral hyperacusis. The association of unilateral hearing loss and ipsilateral hyperacusis is a rare manifestation of a central nervous system lesion. The paradoxical combination of these symptoms strongly suggests pontine dysfunction and prompts urgent neurological evaluation.

Effects of left DLPFC versus right PPC tDCS on multiple sclerosis fatigue.

BACKGROUND AND OBJECTIVE: Fatigue is a frequent and debilitating symptom in patients with multiple sclerosis (MS). Its classical treatments are still faced with limited benefits and numerous side effects. Hence, we aimed to evaluate the effects of transcranial direct current stimulation (tDCS), a noninvasive brain stimulation technique, on such a challenging symptom. Our secondary outcomes included the assessment of tDCS impact on mood and attentional performance. METHODS: Ten fatigued MS patients were enrolled in a double-blind, sham-controlled, and cross-over study. Each patient randomly received three anodal tDCS blocks: active stimulation over the left dorsolateral prefrontal cortex (DLPFC), active stimulation over the right posterior parietal cortex (PPC), and sham stimulation over either cortical site. Both cortical targets are key components in the MS fatigue networks. The blocks consisted of five consecutive daily sessions and were held apart by a washout interval of three weeks. RESULTS: Only active left DLPFC stimulation significantly ameliorated fatigue. Mood improvement was exclusively obtained following active right PPC stimulation. Neither intervention had effects on attention. CONCLUSION: Our study supports the role of anodal tDCS over the left prefrontal in treating MS fatigue. The lack of tDCS effects on attention might be related to the heterogeneity of the studied cohort, the relatively small sample size, the protocol design and duration. Modifying these variables and coupling tDCS with neuroimaging might improve the clinical outcomes and enhance our understanding of the tDCS mechanism of actions.

Miller Fisher syndrome presenting as palate paralysis.

We report a 63-year old patient who presented to our care initially with a hypernasal voice followed by ataxia, ptosis, dysphonia, and paresthesias. The patient's history, physical examination, and additional tests led to a Miller Fisher syndrome (MFS) diagnosis. Palatal paralysis as an inaugurating manifestation of MFS is quite rare and requires special attention from neurologists and otolaryngologists. Although it may present as benign as an acute change in voice, early diagnosis and prompt management may prevent further complications.

The Hand Motor Hotspot is not Always Located in the Hand Knob: A Neuronavigated Transcranial Magnetic Stimulation Study.

The hand motor hot spot (hMHS) is one of the most salient parameters in transcranial magnetic stimulation (TMS) practice, notably used for targeting. It is commonly accepted that the hMHS corresponds to the hand representation within the primary motor cortex (M1). Anatomical and imaging studies locate this representation in a region of the central sulcus called the "hand knob". The aim of this study was to determine if the hMHS location corresponds to its expected location at the hand knob. Twelve healthy volunteers and eleven patients with chronic neuropathic pain of various origins, but not related to a brain lesion, were enrolled. Morphological magnetic resonance imaging of the brain was normal in all participants. Both hemispheres were studied in all participants except four (two patients and two healthy subjects). Cortical mapping of the hand motor area was conducted using a TMS-dedicated navigation system and recording motor evoked potentials (MEPs) in the contralateral first dorsal interosseous (FDI) muscle. We then determined the anatomical position of the hMHS, defined as the stimulation site providing the largest FDI-MEPs. In 45 % of hemispheres of normal subjects and 25 % of hemispheres of pain patients, the hMHS was located over the central sulcus, most frequently at the level of the hand knob. However, in the other cases, the hMHS was located outside M1, most frequently anteriorly over the precentral or middle frontal gyrus. This study shows that the hMHS does not always correspond to the hand knob and M1 location in healthy subjects or patients. Therefore, image-guided navigation is needed to improve the anatomical accuracy of TMS targeting, even for M1.

Repetitive transcranial magnetic stimulation and transcranial direct-current stimulation in neuropathic pain due to radiculopathy: a randomized sham-controlled comparative study.

No study has directly compared the effectiveness of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS) in neuropathic pain (NP). In this 2-centre randomised double-blind sham-controlled study, we compared the efficacy of 10-Hz rTMS and anodal 2-mA tDCS of the motor cortex and sham stimulation contralateral to the painful area (3 daily sessions) in patients with NP due to lumbosacral radiculopathy. Average pain intensity (primary outcome) was evaluated after each session and 5 days later. Secondary outcomes included neuropathic symptoms and thermal pain thresholds for the upper limbs. We used an innovative design that minimised bias by randomly assigning patients to 1 of 2 groups: active rTMS and tDCS or sham rTMS and tDCS. For each treatment group (active or sham), the order of the sessions was again randomised according to a crossover design. In total, 51 patients were screened and 35 (51% women) were randomized. Active rTMS was superior to tDCS and sham in pain intensity (F = 2.89 and P = 0.023). Transcranial direct-current stimulation was not superior to sham, but its analgesic effects were correlated to that of rTMS (P = 0.046), suggesting common mechanisms of action. Repetitive transcranial magnetic stimulation lowered cold pain thresholds (P = 0.04) and its effect on cold pain was correlated with its analgesic efficacy (P = 0.006). However, rTMS had no impact on individual neuropathic symptoms. Thus, rTMS is more effective than tDCS and sham in patients with NP due to lumbosacral radiculopathy and may modulate the sensory and affective dimensions of pain.