Assessment of sacral spinal excitability using stimulus-response curves of the bulbocavernosus reflex.

OBJECTIVE: To analyze and quantify sacral spinal excitability through bulbocavernosus reflex (BCR) stimulus-response curves. METHODS: Thirty subjects with upper motor neuron lesions (UMN) and nine controls were included in this prospective, monocentric study. Sacral spinal excitability was assessed using stimulus-response curves of the BCR, modeled at different bladder filling volumes relative to the desire to void (as defined by the International Continence Society) during a cystometry. Variations in α (i.e. the slope of the stimulus-response curve) were considered as an indicator of the modulation of sacral spinal excitability. RESULTS: In all subjects, α increased during bladder filling suggesting the modulation of spinal sacral excitability during the filling phase. This increase was over 30% in 96.7% of neurological subjects and 88.9% of controls. The increase was higher before the first sensation to void in the neurological population (163.15%), compared to controls, (29.91%), p < 0.001. CONCLUSIONS: We showed the possibility of using BCR stimulus-response curves to characterize sacral spinal response with an amplification of this response during bladder filling as well as a difference in this response amplification in patients with UMN in comparison with a control group. SIGNIFICANCE: BCR, through stimulus-response curves, might be an indicator of pelvic-perineal exaggerated reflex response and possibly a tool for evaluating treatment effectiveness.

The 1316T>C missenses mutation in MTHFR contributes to MTHFR deficiency by targeting MTHFR to proteasome degradation.

5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare hereditary disease characterized by defects in folate and homocysteine metabolism. Individuals with inherited MTHFR gene mutations have a higher tendency to develop neurodegeneration disease as Alzheimer' disease and atherosclerosis. MTHFR is a rate-limiting enzyme catalyzing folate production, various SNPs/mutations in the MTHFR gene have been correlated to MTHFR deficiency. However, the molecular mechanisms underpinning the pathogenic effects of these SNPs/mutations have not been clearly understood. In the present study, we reported a severe MTHFR deficiency patient with late-onset motor dysfunction and sequenced MTHFR gene exons of the family. The patient carries an MD-associating SNP (rs748289202) in one MTHFR allele and the rs545086633 SNP with unknown disease relevance in the other. The rs545086633 SNP (p.Leu439Pro) results in an L439P substitution in MTHFR protein, and drastically decreases mutant protein expression by promoting proteasomal degradation. L439 in MTHFR is highly conserved in vertebrates. Our study demonstrated that p.Leu439Pro in MTHFR is the first mutation causing significant intracellular defects of MTHFR, and rs545086633 should be examined for the in-depth diagnosis and treatment of MD.

Inter- and Intra-Rater Reliability of Laryngeal Sensation Testing with the Touch Method During Flexible Endoscopic Evaluations of Swallowing.

OBJECTIVES: Sensation is an integral component of laryngeal control for breathing, swallowing, and vocalization. Laryngeal sensation is assessed by elicitation of the laryngeal adductor reflex (LAR), a brainstem-mediated adduction of the true vocal folds. During Flexible Endoscopic Evaluations of Swallowing (FEES), the touch method can be used to elicit the LAR to judge laryngeal sensation. Despite the prevalence of this method in clinical practice and research, prior studies have yet to examine inter- and intra-rater reliability. METHODS: Four speech-language pathologists rated 125 randomized video clips for the presence, absence, or inability to rate the LAR. Fifty percent of video clips were re-randomized and re-rated 1 week later. Raters then created guidelines and participated in formal consensus training sessions on a separate set of videos. Ratings were repeated post-training. RESULTS: Overall inter-rater reliability was fair (κ = 0.22) prior to training. Pre-training intra-rater reliability ranged from fair (κ = 0.35) to almost perfect (κ = 0.89). Inter-rater reliability significantly improved after training (κ = 0.42, P < .001), though agreement did not reach prespecified acceptable levels (κ ≥ 0.80). Post-training intra-rater reliability ranged from moderate (κ = 0.49) to almost perfect (κ = 0.85). CONCLUSION: Adequate inter-rater reliability was not achieved when rating isolated attempts to elicit the LAR. Acceptable within-rater reliability was observed in some raters 1 week after initial ratings, suggesting that ratings may remain consistent within raters over a short period of time. Limitations and considerations for future research using the touch method are discussed.

Quadriceps muscle function following anterior cruciate ligament reconstruction: systemic differences in neural and morphological characteristics.

Quadriceps muscle dysfunction is common following anterior cruciate ligament reconstruction (ACLR). Data considering the diversity of neural changes, in-concert with morphological adaptations of the quadriceps muscle, are lacking. We investigated bilateral differences in neural and morphological characteristics of the quadriceps muscle in ACLR participants (n = 11, month post-surgery: 69.4 ± 22.4) compared to controls matched by sex, age, height, weight, limb dominance, and activity level. Spinal reflex excitability was assessed using Hoffmann reflexes (H:M); corticospinal excitability was quantified via active motor thresholds (AMT) and motor-evoked potentials (MEP) using transcranial magnetic stimulation. Cortical activation was assessed using a knee flexion/extension task with functional magnetic resonance imaging (fMRI). Muscle volume was quantified using structural MRI. Muscle strength and patient-reported outcomes were also collected. 2 × 2 RM ANOVAs were used to evaluate group differences. Smaller quadriceps muscle volume (total volume, rectus femoris, vastus medialis, and intermedius) and lower strength were detected compared to contralateral and control limbs. Individuals with ACLR reported higher levels of pain and fear and lower levels of knee function compared to controls. No differences were observed for H:M. ACLR individuals demonstrated higher AMT bilaterally and smaller MEPs in the injured limb, compared to the controls. ACLR participants demonstrated greater activation in frontal lobe areas responsible for motor and pain processing compared to controls, which were associated with self-reported pain. Our results suggest that individuals with ACLR demonstrate systemic neural differences compared to controls, which are observed concurrently with smaller quadriceps muscle volume, quadriceps muscle weakness, and self-reported dysfunction.

A novel exaggerated "spino-bulbo-spinal like" reflex of lower brainstem origin.

BACKGROUND: Many different oligosynaptic reflexes are known to originate in the lower brainstem which share phenomenological and neurophysiological similarities. OBJECTIVE: To evaluate and discuss the differences and aberrancies among these reflexes, which are hard to discern clinically using neurophysiological investigations with the help of a case report. METHODS: We describe the clinical and neurophysiological assessment of a young man who had a childhood history of opsoclonus-myoclonus syndrome with residual mild ataxia and myoclonic jerks in the distal extremities presenting with subacute onset total body jerks sensitive to sound and touch (in a limited dermatomal distribution), refractory to medications. RESULTS: Based on clinical characteristics and insights gained from neurophysiological testing we could identify a novel reflex of caudal brainstem origin. CONCLUSIONS: The reflex described is likely an exaggerated normal reflex, likely triggered by a dolichoectatic vertebral arterial compression and shares characteristics of different reflexes known to originate in caudal brainstem, which subserve distinctive roles in human postural control.

Relationship Between Laryngeal Sensory Deficits, Aspiration, and Pneumonia in Patients with Dysphagia.

The laryngeal adductor reflex (LAR) is an airway protective reflex that manifests as a brief vocal fold closure in response to laryngeal stimulation. This study examined if the absence of the LAR in response to touch delivered by a laryngoscope is associated with penetration/aspiration or pneumonia in patients with dysphagia. Inpatients at a teaching hospital with clinical symptoms of dysphagia were recruited upon referral to the otolaryngology clinic for a swallowing evaluation. Otolaryngologists observed the status of secretions and touched each arytenoid with the tip of the laryngoscope. The patients were then asked to swallow 3-5 mL grape gelatin and 3-5 mL colored water. All procedures were video-recorded. Two independent raters noted absence/presence of the LAR and penetration/aspiration of pharyngeal secretions, gelatin, and water on the recorded videos. A diagnosis of pneumonia during the patient's entire hospital stay was determined by a review of the hospital's medical records. Statistical analyses were performed using Fisher's exact test. Sixty-one patients were included. Twenty-one patients (34.5%) did not exhibit the LAR. No association was found between the absent LAR and penetration or aspiration. There was, however, a significant association between an absence of the LAR and pneumonia development. Patients with an absent LAR had 6.8 times the odds of developing pneumonia as compared to those with a present LAR (OR 6.75; 95% CI 1.76-25.96; p < 0.01). Using the LAR as a marker of laryngeal sensory function appears to be valuable for identifying patients at high risk of pneumonia.

Combined ocular and cervical vestibular evoked myogenic potential in individuals with vestibular hyporeflexia and in patients with Ménière's disease / Potencial evocado miogênico vestibular ocular e cervical simultâneo em indivíduos com hiporreflexia vestibular e em indivíduos com doença de Ménière

Abstract Introduction: The vestibular evoked myogenic potential is a potential of mean latency that measures the muscle response to auditory stimulation. This potential can be generated from the contraction of the sternocleidomastoid muscle and also from the contraction of extraocular muscles in response to high-intensity sounds. This study presents a combined or simultaneous technique of cervical and ocular vestibular evoked myogenic potential in individuals with changes in the vestibular system, for use in otoneurologic diagnosis. Objective: To characterize the records and analyze the results of combined cervical and ocular VEMP in individuals with vestibular hyporeflexia and in those with Ménière's disease. Methods: The study included 120 subjects: 30 subjects with vestibular hyporeflexia, 30 with Ménière's disease, and 60 individuals with normal hearing. Data collection was performed by simultaneously recording the cervical and ocular vestibular evoked myogenic potential. Results: There were differences between the study groups (individuals with vestibular hyporeflexia and individuals with Ménière's disease) and the control group for most of wave parameters in combined cervical and ocular vestibular evoked myogenic potential. For cervical vestibular evoked myogenic potential, it was observed that the prolongation of latency of the P13 and N23 waves was the most frequent finding in the group with vestibular hyporeflexia and in the group with Ménière's disease. For ocular vestibular evoked myogenic potential, prolonged latency of N10 and P15 waves was the most frequent finding in the study groups. Conclusion: Combined cervical and ocular vestibular evoked myogenic potential presented relevant results for individuals with vestibular hyporeflexia and for those with Ménière's disease. There were differences between the study groups and the control group for most of the wave parameters in combined cervical and ocular vestibular evoked myogenic potential.

Resumo Introdução: O potencial evocado miogênico vestibular é um potencial de média latência que avalia a resposta muscular decorrente de estimulação auditiva. Pode ser gerado a partir da contração do músculo esternocleidomastóideo e também a partir da contração de músculos extraoculares em resposta a sons de elevada intensidade. Este estudo apresenta uma técnica combinada ou simultânea de potencial evocado miogênico vestibular cervical e ocular em indivíduos com alterações no sistema vestibular para que possa ser usada no diagnóstico otoneurológico. Objetivo: Caracterizar o registro e analisar os resultados do potencial evocado miogênico vestibular cervical e ocular combinado em indivíduos com hiporreflexia vestibular e em indivíduos com doença de Ménière. Método: Participaram do estudo 120 indivíduos, 30 com hiporreflexia vestibular, 30 com doença de Ménière e 60 com audição dentro dos padrões de normalidade. A coleta de dados foi feita por meio do potencial evocado miogênico vestibular cervical e ocular registrados simultaneamente. Resultados: Houve diferença entre o grupo de estudo (indivíduos com hiporreflexia vestibular e indivíduos com doença de Ménière) e o grupo controle para a maioria dos parâmetros das ondas no potencial evocado miogênico vestibular cervical e ocular combinado. Para o potencial evocado miogênico vestibular cervical observou-se que o prolongamento da latência das ondas P13 e N23 foi a alteração mais encontrada no grupo de indivíduos com hiporreflexia vestibular e no grupo de indivíduos com doença de Ménière. Para o potencial evocado miogênico vestibular ocular o prolongamento da latência das ondas N10 e P15 foi a alteração mais encontrada no grupo de estudo. Conclusão: O potencial evocado miogênico vestibular cervical e ocular combinado apresentou resultados relevantes para os indivíduos com hiporreflexia vestibular e para os indivíduos com doença de Ménière. Houve diferença entre o grupo de estudo e o grupo controle para a maioria dos parâmetros das ondas no potencial evocado miogênico vestibular cervical e ocular combinado.

Altered bulbocavernosus reflex in patients with multiple system atrophy.

OBJECTIVES: Multiple system atrophy (MSA) is characterized by a combination of symptoms including autonomic dysfunction, parkinsonism, cerebellar ataxia, and cortico-spinal disorders. The disease can have either predominant parkinsonism or cerebellar features (MSA-P and MSA-C, respectively). The measurement of the bulbocavernosus reflex (BCR) and pudendal nerve somatosensory-evoked potentials (PSEPs) was originally developed to diagnose diabetic cystopathy and other neuropathologic diseases that share similar symptoms with MSA. We investigated the relationship between abnormalities of neurophysiological parameters and MSA, and estimated the potential value of BCR. METHODS: Fifty-one MSA patients (28 and 23 MSA-P and 23 MSA-C patients, respectively) and 30 healthy controls who were seen at the Department of Neurology were included in the study. A Keypoint EMG/EP system was used to test BCR and PSEPs, and the latencies and amplitudes were recorded for statistical analyses. RESULTS: The BCR was elicited in 78.4% patients with MSA (22/28 MSA-P, 18/23 MSA-C). Prolonged BCR latencies were found in patients with MSA compared with healthy controls (p < 0.001). BCR amplitudes were significantly lower in the MSA group than the control group (p < 0.001). PSEP P41 amplitudes were not significantly different between the MSA and control groups in males (p = 0.608) or females (p = 0.897). There were no significant differences in PSEP latencies among the MSA-P, MSA-C, and control groups (p = 1.0, p = 0.263, and p = 0.060, respectively). DISCUSSION: MSA patients exhibit prolonged BCR latencies and lower amplitudes, which provides a rough anatomical localization of nervous system lesions in MSA patients.

Migraine patients consistently show abnormal vestibular bedside tests / Pacientes enxaquecosos consistentemente apresentam testes vestibulares de beira-de-leito anormais

Migraine and vertigo are common disorders, with lifetime prevalences of 16% and 7% respectively, and co-morbidity around 3.2%. Vestibular syndromes and dizziness occur more frequently in migraine patients. We investigated bedside clinical signs indicative of vestibular dysfunction in migraineurs. Objective To test the hypothesis that vestibulo-ocular reflex, vestibulo-spinal reflex and fall risk (FR) responses as measured by 14 bedside tests are abnormal in migraineurs without vertigo, as compared with controls. Method Cross-sectional study including sixty individuals – thirty migraineurs, 25 women, 19-60 y-o; and 30 gender/age healthy paired controls. Results Migraineurs showed a tendency to perform worse in almost all tests, albeit only the Romberg tandem test was statistically different from controls. A combination of four abnormal tests better discriminated the two groups (93.3% specificity). Conclusion Migraine patients consistently showed abnormal vestibular bedside tests when compared with controls.

Enxaqueca e vertigem são desordens comuns, com prevalência de 16% e 7% respectivamente, e comorbidade em torno de 3,2%. Síndromes vestibulares e tonturas ocorrem mais frequentemente em enxaquecosos. Pesquisamos alterações vestibulares utilizando testes de beira-de-leito em enxaquecosos. Objetivo Verificar se as respostas dos reflexos vestíbulo-ocular, vestíbulo-medular e risco de quedas medidas por 14 testes de beira-de-leito são diferentes comparando-se enxaquecosos sem vertigem, e controles. Método Estudo transversal com sessenta pessoas, 30 enxaquecosos; 25 mulheres, 19-60 anos; e trinta controles saudáveis pareados por sexo e idade. Resultados Houve tendência de pior desempenho entre enxaquecosos em quase todos testes, porém apenas o teste de Romberg tandem foi estatisticamente diferente dos controles. Uma combinação de quatro testes anormais discrimina os grupos com especificidade de 93,3%. Conclusão O grupo de enxaquecosos mostrou consistentemente testes vestibulares de beira-de-leito anormais quando comparados a controles.

The vascular and neurogenic factors associated with erectile dysfunction in patients after pelvic fractures

ABSTRACT Erectile dysfunction (ED) is a common complication of pelvic fractures. To identify the vascular and neurogenic factors associated with ED, 120 patients admitted with ED after traumatic pelvic fracture between January 2009 and June 2013 were enrolled in this study. All patients answered the International Index of Erectile Function (IIEF-5) questionnaire. Nocturnal penile tumescence (NPT) testing confirmed the occurrence of ED in 96 (80%) patients on whom penile duplex ultrasound and neurophysiological testing were further performed. Of these ED patients 29 (30%) were demonstrated only with vascular abnormality, 41 (42.7%) were detected only with neural abnormality, 26 (27.1%) revealed mixed abnormalities. Of the 55 patients (29+26) with vascular problems, 7 patients (12.7%) with abnormal arterial response to intracavernous injection of Bimix (15mg papaverine and 1mg phentolamine), 31 (56.4%) with corporal veno-occlusive dysfunction and 17 (30.9%) had both problems. Of the 67 (41+26) patients with abnormal neurophysiological outcomes, 51 (76.1%) with abnormal bulbocavernosus reflex (BCR), 20 (29.9%) with pathological pudendal nerve evoked potentials (PDEPs) and 25 (37.3%) with abnormal posterior tibial somatosensory nerve evoked potentials (PTSSEPs). Our observation indicated that neurogenic factors are important for the generation of ED in patients with pelvic fracture; venous impotence is more common than arteriogenic ED.

Development of twitching in sleeping infant mice depends on sensory experience.

Myoclonic twitches are jerky movements that occur exclusively and abundantly during active (or REM) sleep in mammals, especially in early development [1-4]. In rat pups, limb twitches exhibit a complex spatiotemporal structure that changes across early development [5]. However, it is not known whether this developmental change is influenced by sensory experience, which is a prerequisite to the notion that sensory feedback from twitches not only activates sensorimotor circuits but modifies them [4]. Here, we investigated the contributions of proprioception to twitching in newborn ErbB2 conditional knockout mice that lack muscle spindles and grow up to exhibit dysfunctional proprioception [6-8]. High-speed videography of forelimb twitches unexpectedly revealed a category of reflex-like twitching-comprising an agonist twitch followed immediately by an antagonist twitch-that developed postnatally in wild-types/heterozygotes, but not in knockouts. Contrary to evidence from adults that spinal reflexes are inhibited during twitching [9-11], this finding suggests that twitches trigger the monosynaptic stretch reflex and, by doing so, contribute to its activity-dependent development [12-14]. Next, we assessed developmental changes in the frequency and organization (i.e., entropy) of more-complex, multi-joint patterns of twitching; again, wild-types/heterozygotes exhibited developmental changes in twitch patterning that were not seen in knockouts. Thus, targeted deletion of a peripheral sensor alters the normal development of local and global features of twitching, demonstrating that twitching is shaped by sensory experience. These results also highlight the potential use of twitching as a uniquely informative diagnostic tool for assessing the functional status of spinal and supraspinal circuits.

Long lasting activity of nociceptive muscular afferents facilitates bilateral flexion reflex pattern in the feline spinal cord.

Chronic muscular limb pain requires the adoption of motor patterns distinct from the classic ipsilateral flexion, crossed extension and corresponding reciprocal inhibitions to acute exteroceptive stimulation. Using selective chemical activation of group III/IV afferents in gastrocnemius-soleus (GS) muscles we investigated bilaterally their reflex responses conditioned by (a) acute 'myositis' induced by intramuscular carrageenan; and (b) sub-acute 'myositis' induced by infusion of complete Freund's adjuvant (CFA). Reflex transmission was detected by monosynaptic testing and c-fos staining used to identify increased neuronal activity. In all control experiments with chemical stimulation of group III/IV afferents, ipsilateral responses conformed to the flexor reflex pattern. However, the expected contralateral facilitation of GS motoneurones occurred in fewer than 50% trials while only 9% of trials induced contralateral inhibition of flexor posterior-biceps-semitendinosus (PBSt) motoneurones. During carrageenan acute myositis contralateral PBSt was transiently facilitated by selective activation of group III/IV afferents. During CFA-induced myositis, contralateral only inhibition of GS motoneurones occurred instead of any facilitation, while bidirectionally a crossed facilitation of PBST dominated. These reflex changes were mirrored in an enhanced number of neurones with enhanced c-fos expression. Muscle pain, particularly if chronically persistent, requires another behavioural response pattern than acute exteroceptive pain.

Social interaction with a cagemate in pain facilitates subsequent spinal nociception via activation of the medial prefrontal cortex in rats.

Empathy for the pain experience of others can lead to the activation of pain-related brain areas and can even induce aberrant responses to pain in human observers. Recent evidence shows this high-level emotional and cognitive process also exists in lower animals; however, the mechanisms underlying this phenomenon remain unknown. In the present study we found that, after social interaction with a rat that had received subcutaneous injection of bee venom (BV), only the cagemate observer (CO) but not the noncagemate observer (NCO) showed bilateral mechanical hypersensitivity and an enhanced paw flinch reflex following BV injection. Moreover, neuronal activities labeled by c-Fos immunoreactivity in the spinal dorsal horn of CO rats were also significantly increased relative to the control 1 hour after BV injection. A stress-related response can be excluded because serum corticosterone concentration following social interaction with demonstrator rats in pain was not changed in CO rats relative to NCO and isolated control rats. Anxiety can also be excluded because anxiety-like behaviors could be seen in both the CO and NCO rats tested in the open-field test. Finally, bilateral lesions of the medial prefrontal cortex eliminated the enhancement of the BV-induced paw flinch reflex in CO rats, but bilateral lesions of either the amygdala or the entorhinal cortex failed. Together, we have provided another line of evidence for the existence of familiarity-dependent empathy for pain in rats and have demonstrated that the medial prefrontal cortex plays a critical role in processing the empathy-related enhancement of spinal nociception.

Clinical and urodynamic evaluation of women referred with diabetes mellitus.

INTRODUCTION AND HYPOTHESIS: We investigated the impact of diabetes mellitus (DM) on female lower urinary tract dysfunction. METHODS: We prospectively collected data of 1,640 consecutive diabetic women from the inpatient departments and outpatient clinics of urology, endocrinology, geriatrics, and nephrology in primary, secondary, and tertiary referral hospitals, rural healthcare stations, and nursing homes in Dujiangyan, China. Clinical histories were taken on an individualized basis depending on patient presentation. Urodynamics were performed in the enrolled female diabetic patients after excluding other causes of lower urinary tract dysfunction. Data on lower urinary tract symptoms and urodynamic parameters were analyzed. RESULTS: Ninety-three percent of diabetic women complained of lower urinary tract symptoms, and 88 % had positive urodynamic findings. Sixty-three percent presented with storage symptoms, 918 cases of which had detrusor overactivity, 787 impaired detrusor contractility, and 131 detrusor areflexia. Among the 918 patients with impaired detrusor contractility or detrusor areflexia, the mean first sensation of filling was 238.1 ml, with a mean maximum cystometric capacity of 624 ml, mean maximum flow rate of 9.6 ml/s, mean detrusor pressure at maximum flow rate of 32.4 cmH2O, and mean postvoid residual of 323 ml. Thirty-eight of 131 patients with detrusor areflexia had impaired renal function on blood chemistry test, and massive bilateral ureterohydronephrosis and "Christmas-tree-shaped" bladder in videourodynamic studies. On the whole, 95 % diabetic women had diabetic cystopathy. CONCLUSIONS: DM alters voiding patterns significantly, causing various lower urinary tract symptoms in a significant proportion of diabetic women. Diabetic cystopathy is a progressive condition with a spectrum of clinical symptoms and urodynamic findings. The prevalence of diabetic cystopathy is very high in Dujiangyan, China.

Non-invasive serial casting to treat idiopathic toe walking in an 18-month old child.

BACKGROUND: Idiopathic toe walking is characterized by persistent toe walking in the absence of clinically diagnosed neuromuscular disease. Treatment options in children diagnosed with idiopathic toe walking include: observation, physical therapy, serial casting, or Achilles tendon (heel cord) lengthening surgery. OBJECTIVE: In this case report, we present a non-invasive serial casting protocol to treat severe and persistent toe walking in an 18-month old child, diagnosed as an idiopathic toe walker following neurological examination. METHODS: A series of below knee casts was used to provide a consistent stretch to the plantar flexor muscles. Upon removal of each set of casts, passive range of motion at the ankles was measured with a goniometer. RESULTS: Four sets of casts, each lasting approximately one week, increased passive ankle dorsiflexion to 10° of neutral and established a heel-toe walking gait. Improvements in ankle range of motion and gait were maintained upon repeated examinations at 3, 7, and 12 months post-casting. CONCLUSIONS: These results demonstrate that non-invasive procedures, such as serial casting, can be successful in very young children diagnosed as idiopathic toe walkers. Early identification and intervention for this diagnosis may eliminate the need for invasive surgeries and associated risks in this population.