Anodal tDCS of the swallowing motor cortex for treatment of dysphagia in multiple sclerosis: a pilot open-label study.

Swallowing difficulties are a common symptom of multiple sclerosis (MS). The early detection and treatment of dysphagia is critical to prevent complications, including poor nutrition, dehydration, and lung infections. Recently, transcranial direct current stimulation (tDCS) has been proven to be effective in ameliorating swallowing problems in stroke patients. In this pilot study, we aimed to assess safety and efficacy of transcranial direct current stimulation (tDCS) in the treatment of dysphagia in MS patients. We screened 30 patients by using the 10-item DYsphagia in MUltiple Sclerosis (DYMUS) questionnaire, and patients at risk for dysphagia underwent a clinical and fiberoptic endoscopic evaluation of swallowing (FEES). Six patients who presented with mild to moderate dysphagia underwent the experimental procedures. These consisted of 5 sessions of anodal tDCS applied in consecutive days over the right swallowing motor cortex. Patients were followed-up at 1 week, 1 month and 3 months after treatment, and changes in the Dysphagia Outcome and Severity Scale (DOSS) score between baseline and post-tDCS were assessed. Our results showed that in all patients, the tDCS treatment determined a mild but significant clinical benefit (one-point improvement in the DOSS score) lasting up to 1 month. In conclusion, our preliminary results show that anodal tDCS has therapeutic potential in the treatment of swallowing problems in patients suffering with MS. However, future double-blind, randomized, and sham-controlled studies are needed to confirm the present findings.

Evidence Based Design and healthcare: an unconventional approach to hospital design.

Evidence Based Design (EBD) is a scientific analysis methodology that emphasises the use of data acquired in order to influence the design process in hospitals. It measures the physical and psychological effects of the built environment on its users. EBD uses formularization of hypothesis, testing/analyzing and outcome gathering as a framework. The design practice, in general, has always been based on a combination of legal, technical/ functional/ and aesthetical knowledge. This generalization has been shifted to another level after the implementation of EBD. In the last 30 years many case studies were collected which demonstrate the built environment's impact on users. EBD methodology can be applied to any type of building, but it is particularly used to analyze the efficiency of healthcare facilities. The Goal of this paper is to demonstrate various applications of EBD principles in healthcare buildings through case studies concerning: - reduction of infections - reduction of stress on medical staff - improved patient healing In addition to the analysis of case studies, we will also focus on official EBD researches developed by healthcare designers and professionals as "alternative solutions". These alternative "ad hoc" solutions are developed in order to answer EBD research results. The solutions that are developed from the results can answer the real needs of each hospital and improve best technological practice to reduce infection, stress and improve patient comfort. Abroad the EBD research results are studied and used by many contemporary hospital architects to develop new solutions to meet the specific requirements of any hospital project they are currently designing. This procedure demonstrates that for each outcome and key finding, there is always at least one alternative solution and, therefore, the achievement of a new hypothesis, case studies to test/measure and outcome to gather occurs. This repetitive attitude leads to a "virtuous circle" where the development of new samples produces a double- positive effect in both EBD research (in terms of new case studies to analyze) and in EBD lessons for implementation in various hospitals. Through this paper the authors state that the combined effort is needed by EBD practitioners, healthcare architects and hospital managers for the improvement and diffusion of EBD in healthcare, especially in Italy where this methodology is not widely used.

An electrophysiological approach to the diagnosis of neurogenic dysphagia: implications for botulinum toxin treatment.

OBJECTIVES: Botulinum toxin (BTX) injection into the cricopharyngeal (CP) muscle has been proposed for the treatment of neurogenic dysphagia due to CP hyperactivity. The aim was to determine whether an electrophysiological method exploring oropharyngeal swallowing could guide treatment and discriminate responders from non-responders, based on the association of CP dysfunction with other electrophysiological abnormalities of swallowing. METHODS: Patients with different neurological disorders were examined: Parkinson disease, progressive supranuclear palsy, multiple system atrophy-Parkinson variant, multiple system atrophy cerebellar variant, stroke, multiple sclerosis and ataxia telangiectasia. All patients presented with clinical dysphagia, and with complete absence of CP muscle inhibition during the hypopharyngeal phase of swallowing. Each patient underwent clinical and electrophysiological investigations before and after treatment with BTX into the CP muscle of one side (15 units of Botox). Clinical and electrophysiological procedures were performed in a blind manner by two different investigators. The following electrophysiological measures were analysed: (1) duration of EMG activity of suprahyoid/submental muscles (SHEMG-D); (2) duration of laryngopharyngeal mechanogram (LPM-D); (3) duration of the inhibition of the CP muscle EMG activity (CPEMG-ID); and (4) interval between onset of EMG activity of suprahyoid/submental muscles and onset of laryngopharyngeal mechanogram (I-SHEMG-LPM). RESULTS: Two months after treatment, 50% of patients showed a significant improvement. Patients with prolonged or reduced SHEMG-D values and prolonged I-SHEMG-LPM values did not respond to BTX. Therefore, values for which BTX had no effect (warning values) were identified. CONCLUSIONS: This electrophysiological method can recognise swallowing abnormalities which may affect the outcome of the therapeutic approach to dysphagia with BTX treatment.

The importance of the reproducibility of oropharyngeal swallowing in amyotrophic lateral sclerosis. An electrophysiological study.

OBJECTIVE: To investigate electrophysiologically the reproducibility of oropharyngeal swallowing in patients with ALS. METHODS: We enrolled 26 ALS patients, both with and without clinical signs of dysphagia, and 30 age-matched controls. The reproducibility of the electrophysiological signals related to the oral phase (electromyographic activity of the submental/suprahyoid muscles) and the pharyngeal phase (laryngeal-pharyngeal mechanogram) of swallowing across repeated swallows was assessed. To do this we computed two similarity indexes (SI) by using previously described mathematical algorithms. RESULTS: The reproducibility of oropharyngeal swallowing was significantly reduced both in patients with and in those without clinical signs of dysphagia, with more marked alterations being detected in the dysphagic group. The SI of both phases of swallowing, oral and pharyngeal, correlated significantly with dysphagia severity and disease severity. CONCLUSIONS: In ALS different pathophysiological mechanisms can alter the stereotyped motor behaviors underlying normal swallowing, thus reducing the reproducibility of the swallowing act. A decrease in swallowing reproducibility could be a preclinical sign of dysphagia and, beyond a certain threshold, a pathological hallmark of oropharyngeal dysphagia. SIGNIFICANCE: Electrophysiological assessment is a simple and useful tool for the early detection of swallowing abnormalities, and for the management of overt dysphagia in ALS.

Laryngeal and phrenic nerve involvement in a patient with hereditary neuropathy with liability to pressure palsies (HNPP).

Lower cranial and phrenic nerve involvement is exceptional in hereditary neuropathy with liability to pressure palsies (HNPP). Here we report the occurrence of reversible laryngeal and phrenic nerve involvement in a patient with HNPP. The patient recalled several episodes of reversible weakness and numbness of his feet and hands since the age of 30 years. His medical history was uneventful, apart from chronic obstructive pulmonary disease (COPD). At age 44, following severe weight loss, he presented with progressive dysphonia and hoarseness. EMG of cricoarytenoid and thyroarytenoid muscles and laryngeal fibroscopy confirmed vocal cord paralysis. These speech disturbances gradually regressed. Two years later, he reported rapidly worsening dyspnea. Electroneurography showed increased distal latency of the right phrenic nerve and diaphragm ultrasonography documented reduced right hemi-diaphragm excursion. Six months later and after optimization of CODP treatment, his respiratory function had improved and both phrenic nerve conduction and diaphragm excursion were completely restored. We hypothesize that chronic cough and nerve stretching in the context of CODP, together with severe weight loss, may have triggered the nerve paralysis in this patient. Our report highlights the need for optimal management of comorbidities such as CODP as well as careful control of weight in HNPP patients to avoid potentially harmful complications.

Specific patterns of laryngeal electromyography during wakefulness are associated to sleep disordered breathing and nocturnal stridor in multiple system atrophy.

BACKGROUND: Nocturnal stridor and respiratory abnormalities are important features of multiple system atrophy (MSA) with relevance to patient survival, and they are detected and evaluated mainly through video-polysomnography (video-PSG). Diurnal laryngoscopy seems to yield abnormal findings only in the presence of significant vocal cord (VC) dysfunction. AIM: To assess whether specific electrophysiological patterns of diurnal EMG of VC muscles may indicate nocturnal stridor or respiratory dysfunctions in MSA patients. MATERIALS AND METHODS: Seventeen patients with probable MSA were examined. A full-night video-PSG to collect standard breathing parameters (apnea/hypopnea index, mean HbSAO2, oxygen desaturation index, total sleep time with HbSaO2 below 90%) was performed in all the patients. Laryngoscopy and EMG investigation of adductor (thyroarytenoid-TA) and abductor (posterior cricoarytenoid-PCA) muscles of the VCs were also performed. RESULTS: Both the laryngeal EMG abnormalities (based on MUAP analysis and kinesiologic EMG investigation of VC muscles) and the laryngoscopic alterations correlated with video-PSG respiratory abnormalities. Specific patterns of EMG findings were consistently found in MSA subjects with nocturnal stridor detected at PSG. In particular, the following EMG findings were related to the severity of breathing abnormalities and the presence of stridor on video-PSG: neurogenic pattern on MUAP analysis of the PCA, paradoxical activation of the TA during inspiration and tonic EMG activity of the TA during quiet breathing. CONCLUSIONS: Electromyographic/kinesiologic investigation of VC muscles during wakefulness provides additional information on the pathophysiology of the respiratory abnormalities in MSA patients that could be useful for guiding the choice of the best appropriate treatment and care.

Combined central and peripheral demyelination: Clinical features, diagnostic findings, and treatment.

Combined central and peripheral demyelination (CCPD) is rare, and current knowledge is based on case reports and small case series. The aim of our study was to describe the clinical features, diagnostic results, treatment and outcomes in a large cohort of patients with CCPD. Thirty-one patients entered this retrospective, observational, two-center study. In 20 patients (65%) CCPD presented, after an infection, as myeloradiculoneuropathy, encephalopathy, cranial neuropathy, length-dependent peripheral neuropathy, or pseudo-Guillain-Barré syndrome. Demyelinating features of peripheral nerve damage fulfilling European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) electrodiagnostic criteria for CIDP were found in 23 patients (74%), and spatial dissemination of demyelinating lesions on brain MRI fulfilling the 2010 McDonald criteria for multiple sclerosis (MS) in 11 (46%). Two thirds of the patients had a relapsing or progressive disease course, usually related to the appearance of new spinal cord lesions or worsening of the peripheral neuropathy, and showed unsatisfactory responses to high-dose corticosteroids and intravenous immunoglobulins. The clinical presentation of CCPD was severe in 22 patients (71%), who were left significantly disabled. Our data suggest that CCPD has heterogeneous features and shows frequent post-infectious onset, primary peripheral nervous system or central nervous system involvement, a monophasic or chronic disease course, inadequate response to treatments, and a generally poor outcome. We therefore conclude that the current diagnostic criteria for MS and CIDP may not fully encompass the spectrum of possible manifestations of CCPD, whose pathogenesis remains largely unknown.

Clustering of ALS patients in central Italy due to the occurrence of the L84F SOD1 gene mutation.

OBJECTIVE: To study three new apparently unrelated Italian families with ALS and several sporadic ALS patients living in the same rural area. BACKGROUND: One Italian family with ALS carrying a superoxide dismutase 1 (SOD1) gene mutation (G41S) and no regional ALS clustering has been reported in Italy. METHODS: Genetic analysis was performed by automated and manual sequencing of the SOD1 gene in 13 family members and in 6 of 10 unrelated patients with sporadic cases of ALS living in the same area. The authors also determined SOD1 activity in erythrocytes and lymphocytes. RESULTS: The three families included a total of 28 affected members distributed over six generations. Despite a wide variability in age at onset and disease duration, the clinical pattern is uniform, with onset in the lower limbs, ascending progression, and predominant lower motor neuron involvement in all subjects. Generational anticipation is evident in the last two generations. All familial ALS patients and one of the six sporadic patients carry the same L84F missense point mutation in exon 4 of the SOD1 gene. SOD1 enzyme activity and SOD1 protein levels were not decreased significantly in the L84F patients. CONCLUSION: The ALS patients carrying the L84F mutation derive from a common ancestor. This mutation is responsible for ALS clustering in the area. The L84F mutation does not modify SOD1-specific activity.

Effects of sleep on spinal nociceptive reflexes in humans.

Controversy continues to surround the monosynaptic and polysynaptic spinal reflexes during the different stages of sleep. In animal studies both of these reflexes were found to be depressed during desynchronized sleep. In humans, the H reflex was unchanged whereas the second component of the nociceptive flexion reflex was increased. However, abolition of the H reflex and F waves during REM sleep has also been reported. The aim of this investigation was to examine the effects of different sleep stages on the polysynaptic nociceptive flexion reflex. Six healthy volunteers were studied. The RIII reflex was studied according to Willer's method (1977) during the different stages of NREM and REM sleep. The RIII reflex threshold was found to increase during stage 2 of NREM sleep. It remained higher during stages 3 and 4. During REM sleep a further increase in the reflex threshold was observed. The reflex latency was prolonged during stage 4 of NREM sleep. There was evidence of further latency prolongation during REM sleep. It was also during REM sleep that the maximum increase in the amplitude and duration of the reflex were recorded.

Evidence for serotonin-S2 receptor involvement in analgesia in humans.

The possible analgesic activity of ritanserin (a new very selective and potent serotonin-S2 antagonist) was studied (double-blind) in humans. A significant increase in nociceptive flexion reflex threshold and subjective pain threshold was observed after five days of treatment, while treatment with placebo did not induce any change. The effects of ritanserin were not reversed by either naloxone or saline (double-blind) administration. Our data suggest a possible role of serotonin-S2 receptors in analgesia.

Periodic alternating nystagmus and vestibulo-spinal system facilitating activity.

OBJECTIVE: Periodic alternating nystagmus has been associated with the instability of the velocity storage mechanism, which is known to play an important role in both the vestibulo-oculomotor and the optokinetic systems. In the present study we looked for a possible spinal equivalent to PAN. METHODS AND RESULTS: In 3 PAN patients, the H-reflex amplitude proved to be slightly but significantly influenced by nystagmus direction, in that it was greater when the nystagmus was beating toward the stimulation side. CONCLUSIONS: This finding suggests that projections from velocity storage may play a role not only in the ocular motor but also in assisting postural stability through the vestibulo-spinal system.

Proximal nerve conduction by high-voltage electrical stimulation in S1 radiculopathies and acquired demyelinating neuropathies.

OBJECTIVE: To evaluate the reliability and sensitivity of the high-voltage electrical stimulation for studying proximal conduction of peripheral motor axons in normal subjects, S(1) radiculopathies and acquired demyelinating neuropathies. METHODS: Twelve patients with compressive S(1) radiculopathy, 22 patients with acquired demyelinating neuropathy and 29 healthy volunteers were examined. The conduction of peripheral motor axons between lumbosacral roots and the sciatic nerve at the gluteal fold was investigated by high-voltage electrical stimulation delivered percutaneously. RESULTS: The main electrophysiological finding in S(1) radiculopathy was an abnormal side to side difference in the amplitude of the compound motor action potential by proximal stimulation. Overall, the frequency of abnormalities detected by using high-voltage electrical stimulation was similar to that found with conventional EMG studies, and the two methods showed electrophysiological alterations in the same patients. In all patients with acquired demyelinating neuropathy, the proximal motor nerve conduction velocity from lumbosacral roots to the sciatic nerve at the gluteal fold was reduced; proximal stimulation of the motor axons revealed electrophysiological abnormalities more often than when using other electrophysiological techniques (F wave and H reflex). CONCLUSIONS: High-voltage electrical stimulation of peripheral motor axons shows high sensitivity in detecting proximal neuropathies; it can also define the site and relevance of proximal lesions in the peripheral nervous system better than other conventional techniques.

Different effect of high doses of naloxone on spinal reflexes in normal subjects and chronic paraplegic patients.

There is still controversy over the effects of naloxone on spinal reflexes in view of the fact that both facilitatory and inhibitory activities have been observed. Dosage, supraspinal influences and interactions with different opiate receptors may account for the different findings. We investigated the effect of placebo (saline) and high doses of naloxone (1.66 mg/kg) on the monosynaptic (H reflex) and nociceptive polysynaptic reflex (RIII reflex) in five normal subjects and three chronic paraplegic subjects. Following the administration of naloxone, there were no changes in the RIII reflex threshold in either group. By contrast, there was a marked facilitation of the H reflex amplitude in the normal subjects, but not in the spinal cord-injured subjects after treatment with naloxone. Saline induced no changes in the RIII reflex threshold or the H reflex amplitude in either of the two groups. Our data suggest that under normal conditions the opiatergic modulation of the nociceptive reflex is not functionally active whereas the tonic inhibitory modulation of the monosynaptic reflex is mediated by descending pathways.

Electrophysiologic study of central motor pathways in ataxia-telangiectasia.

To date, corticospinal tract functional integrity in ataxia-telangiectasia has not been studied. Thorough evaluation of central motor pathways is also lacking in neuropathologic and clinical studies. Using electromagnetic stimulation, we assessed the integrity of the corticospinal tracts in eight patients with ataxia-telangiectasia. Cortical and peripheral compound motor action potentials were recorded from the abductor pollicis brevis muscle. Recordings of the shortest F-wave latency and of the compound motor action potential distal latency were made from the abductor pollicis brevis muscle after electrical stimulation of the median nerve at the wrist. A significant increase in central motor conduction time was observed in four patients, two of whom had clinical findings compatible with a pyramidal lesion. This study demonstrates involvement of the central motor pathways in ataxia-telangiectasia, which appears to be more frequent late in the course of the disease.

Neurophysiological markers of central and peripheral involvement of the nervous system in HIV-infection.

Peroneal motor and sural sensory conduction velocities (MNCVs/SNCVs), somatosensory evoked potentials to median nerve stimulation (MN-SEPs) and motor evoked potentials (MEPs) to transcranial stimulation were examined in 138 HIV-infected patients (in the different stages of the disease), 20 seronegative intravenous drug abusers (IVDAs), and 20 healthy subjects. Findings of peroneal MNCV slowing in patients ranged from 16% (asymptomatic HIV patients) to 63% (AIDS) and of sural SNCV slowing from 13% to 40%. Altered MN-SEPs ranged from 10% to 30%, and MEPs ranged from 44% to 72%, mostly due to a prolongation of the central motor conduction time (CMCT). All seronegative IVDAs showed patterns within the normal range. Electrophysiological techniques were helpful in demonstrating early and subclinical alterations in HIV patients.

Acute i.v. vincamine teprosilate administration: quantified investigation in elderly subjects.

The EEG changes in elderly subjects with chronic cerebrovascular disorders (CCVD) are well known and have been described by many authors. Vincamine teprosilate (Teproside), a drug supposed to act on the electrical activity of the brain, has the properties of modifying and, to some extent, improving age-related changes. Ten subjects, whose age ranged from 60 to 70 years, underwent the trial. Each received 1 ampoule i.v. of the active drug and 1 ampoule of placebo (or vice versa) after a 48-hour wash-out period, according to a double-blind randomized schedule. EEG recordings were performed at time 0 and then 30 min, 1 h, 2 h, and 4 h after injection. A double effect of vincamine teprosilate could be observed at the quantified EEG: 1) an early effect, i.e., an improvement of the EEG pattern within the first hour following administration; and (2) a slow-occurring effect that prevented negative EEG modifications from taking place at the fourth hour following administration.

[The role of drug therapy in the treatment of nerve root lesions caused by compression. Clinical and electrophysiological study of 30 patients operated on for the removal of herniated disks]. / Ruolo della terapia farmacologica nel trattamento delle lesioni radicolari da compressione. Studio clinico ed elettrofisiologico in 30 pazienti operati di asportazione di ernia discale.

The therapeutic efficacy of two neurotrophic substances (exogenic gangliosides and Vitamin B12) is examined in 30 cases of patients suffering from postoperative radiculopathy after the excision of herniated discs. All patients were subjected to clinical examination as well as electromyography and electroneuronography. Check-ups 10 and 60 days after surgery revealed a much greater improvement among the treated than the untreated patients and that statistically significant clinical and electrophysiological improvement was only found among those treated with exogenic gangliosides.

Bilateral sympathetic skin response following nociceptive stimulation: study in healthy individuals.

Bilateral sympathetic skin response (SSR) was evaluated in 25 normal subjects aged (29 +/- 5 years). The stimulation (an electrical pulse train randomly applied to the sural nerve) was equal to 0.5-1.0-1.5 times the nociceptive flexion reflex (RIII) thresholds. This method allowed us to quantify the pain threshold, since a close relationship between the RIII threshold and subjective pain threshold has been described. Decrease in latency, increase in amplitude and duration were observed when increasing intensity of stimulation was used. The right-side stimulation produced significantly shorter latencies and higher amplitudes than the left one. The asymmetry index showed a trend of larger responses on the left hand and shorter latencies on the right hand in males. Females displayed less left-right asymmetry than males. A positive correlation was recognized between RIII threshold and amplitude and duration of SSR. Test-retest evaluation in 12 individuals revealed good reproducibility of SSR in terms of latency and duration, while amplitudes showed large variability. The accuracy of SSR response concerning latency and duration was better (range 0.88-0.92) when 1.5 RIII threshold was used, showing that painful stimulation should be used to obtain reliable SSR in clinical practice.

Local venous lactate changes and spectral analysis of surface EMG during fatiguing isometric efforts in intrinsic hand muscles.

In this study relationships between local venous lactate concentrations and power spectrum changes in surface EMG due to fatiguing isometric contractions were investigated. Two different isometric efforts of the opponents pollicis muscle, 25% and 50% of maximum voluntary contraction, were examined. In 25% of maximum voluntary contraction no changes in local venous lactate were observed, whereas mean power frequency values of surface EMG shifted significantly towards lower frequencies. On the contrary, in 50% of maximum voluntary contraction lactate significantly increased and was related to the mean power frequency shifts of the surface EMG. These data suggest that lactate plays a role in muscle fatigue only in a limited intensity range of isometric muscle contractions.