[Clinical features of CAPOS syndrome caused by maternal ATP1A3 gene variation: a case report].

CAPOS syndrome is an autosomal dominant neurological disorder caused by mutations in the ATP1A3 gene. Initial symptoms, often fever-induced, include recurrent acute ataxic encephalopathy in childhood, featuring cerebellar ataxia, optic atrophy, areflflexia, sensorineural hearing loss, and in some cases, pes cavus. This report details a case of CAPOS syndrome resulting from a maternal ATP1A3 gene mutation. Both the child and her mother exhibited symptoms post-febrile induction,including severe sensorineural hearing loss in both ears, ataxia, areflexia, and decreased vision. Additionally, the patient's mother presented with pes cavus. Genetic testing revealed a c. 2452G>A（Glu818Lys） heterozygous mutation in theATP1A3 gene in the patient . This article aims to enhance clinicians' understanding of CAPOS syndrome, emphasizing the case's clinical characteristics, diagnostic process, treatment, and its correlation with genotypeic findings.

Knockdown of calpain1 in lumbar motoneurons reduces spasticity after spinal cord injury in adult rats.

Spasticity, affecting ∼75% of patients with spinal cord injury (SCI), leads to hyperreflexia, muscle spasms, and cocontractions of antagonist muscles, greatly affecting their quality of life. Spasticity primarily stems from the hyperexcitability of motoneurons below the lesion, driven by an upregulation of the persistent sodium current and a downregulation of chloride extrusion. This imbalance results from the post-SCI activation of calpain1, which cleaves Nav1.6 channels and KCC2 cotransporters. Our study was focused on mitigating spasticity by specifically targeting calpain1 in spinal motoneurons. We successfully transduced lumbar motoneurons in adult rats with SCI using intrathecal administration of adeno-associated virus vector serotype 6, carrying a shRNA sequence against calpain1. This approach significantly reduced calpain1 expression in transduced motoneurons, leading to a noticeable decrease in spasticity symptoms, including hyperreflexia, muscle spasms, and cocontractions in hindlimb muscles, which are particularly evident in the second month post-SCI. In addition, this decrease, which prevented the escalation of spasticity to a severe grade, paralleled the restoration of KCC2 levels in transduced motoneurons, suggesting a reduced proteolytic activity of calpain1. These findings demonstrate that inhibiting calpain1 in motoneurons is a promising strategy for alleviating spasticity in SCI patients.

Marcus-Gunn jaw winking syndrome: case series study and management algorithm.

PURPOSE: To identify a rationale for treatment of patients with Marcus Gunn jaw winking syndrome (MGJWS). METHODS: Retrospective review of 38 consecutive patients with MGJWS referred to a single tertiary institution. Clinical data included visual acuity, ocular motility, side of jaw-wink, presence or absence of ptosis, levator function, clinical photographs, and management undertaken. Thirty-two patients were operated on with customized surgery by a senior surgeon (FQL). RESULTS: Cases with no ptosis or mild ptosis were managed conservatively. Levator advancement (LA) was successful in case of moderate ptosis and negligible synkynesis but resulted in a more evident synkinesis. Levator resection (LR) in patients with severe ptosis was associated with high rate of ptosis recurrence. Ptosis was adequately corrected in all patients submitted to uni- or bilateral levator excision (LE) and bilateral frontalis suspension (FS) or unilateral frontalis flap (FF). Jaw winking resolved in all patients submitted to LE but recurred in three cases at a later stage. Strabismus surgery was performed simultaneously in case of associated esotropia or hypotropia. CONCLUSIONS: Moderate ptosis can be corrected with LA, but success is not related to levator function and synkinesis becomes more evident postoperatively. In severe ptosis, LR showed unpredictable results. In case of severe ptosis and severe synkinesis, uni- or bilateral LE and bilateral FS are recommended; unilateral FF is an alternative in patients who refuse bilateral treatment, as the cosmetic outcome is usually better than after unilateral FS.

Effect of electroacupuncture on urodynamics and Raf/MEK/ERK signaling pathway in spinal cord tissue of rats with detrusor hyperreflexia after suprasacral spinal cord injury. / ç”µé’ˆå¯¹éª¶ä¸Šè„Šé«“æŸä¼¤åŽé€¼å°¿è‚Œåå°„äº¢è¿›åž‹å¤§é¼ å°¿æµåŠ¨åŠ›å­¦åŠè„Šé«“Raf/MEK/ERK信号通路的影响.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on urodynamics and Raf/MEK/ERK signaling pathway in spine cord tissue of rats after suprasacral spinal cord injury (SSCI), so as to explore its possible mechanism in improving bladder function in rats with detrusor hyperreflexia after SSCI. METHODS: Female SD rats were randomly divided into blank, sham operation, model, EA and EA+PD98059 groups, with 12 rats in each group. Thorax (T) 10 spinal cord transection was performed by surgery. Rats in the EA group were given EA (10 Hz/50 Hz, 20 min) at "Ciliao" (BL32), "Zhongji" (CV3), "Sanyinjiao" (SP6) and "Dazhui" (GV14) once daily for 7 d. Rats of the EA+PD98059 group received intraperitoneal injection of PD98059 (5 mg/kg) 2 h before EA intervention. The urodyna-mics was used to measure the base pressure, leak point pressure, maximum pressure, maximum capacity and comp-liance of bladder, and the morphology of bladder detrusor tissue was observed with HE staining. The TUNEL staining was used to detect the cell apoptosis of the spinal cord tissue. The expression levels of exchange protein directly activated by cAMP 2 (Epac2), Rap, phosphorylated rapidly accelerated fibrosarcoma (p-Raf), phosphorylated mitogen-activated extracellular signal-regulated kinase (p-MEK), phosphorylated extracellular signal regulated kinase 1 and 2 (p-ERK1/2), B-cell lymphoma-2 (Bcl-2), and Bcl-2 associated X protein (Bax) were determined by Western blot. RESULTS: Compared with the sham operation group, the base pressure, leak point pressure and maximum pressure of bladder were significantly increased (P<0.01), the maximum bladder capacity and bladder compliance were decreased (P<0.01), the cell apoptosis rate of spinal cord tissue was increased (P<0.01), and the expression levels of Epac2, Rap, p-Raf, p-MEK, p-ERK1/2, and Bcl-2 protein in spinal cord tissue were decreased (P<0.01), while the expression level of Bax protein was increased (P<0.01) in the model group. After the treatment and compared with the model group, the base pressure, leak point pressure and maximum pressure of bladder, the cell apoptosis rate of spinal cord tissue, the expression level of Bax protein were decreased (P<0.05) in the EA group, while the maximum bladder capacity and bladder compliance, the expression levels of Epac2, Rap, p-Raf, p-MEK, p-ERK1/2, and Bcl-2 protein in spinal cord tissue were all increased (P<0.05, P<0.01). In comparison with the EA group, the base pressure, leak point pressure and maximum pressure of bladder, the cell apoptosis rate, the expression level of Bax protein were significantly increased (P<0.05), whereas the maximum bladder capacity, bladder compliance, and the expression levels of p-MEK, p-ERK1/2, and Bcl-2 protein were decreased (P<0.05) in the EA+PD98059 group. Results of HE staining showed disordered transitional epithelial cells and destroyed lamina propria in bladder detrusor tissue, with the infiltration of monocytes in the model group, which was obviously milder in both EA and EA+PD98059 groups, especially in the EA group. CONCLUSIONS: EA can improve the bladder function in detrusor hyperreflexia rats after SSCI, which may be related to its effect in up-regulating Epac2 and Rap, activating the Raf-MEK-ERK pathway, and reducing the cell apoptosis of spinal cord tissue.

Non-Hodgkin's Lymphoma with Intraspinal Involvement Mimics Bilateral Thoracolumbar Plexopath.

PURPOSE: Non-Hodgkin lymphoma (NHL) is the most common type of lymphoma, and its extranodal manifestation is rare. Skeletal muscle involvement is noted in only 1.1% of patients with NHL. Here, we present a case of high-grade B-cell lymphoma (HGBL); it infiltrated the left neural foramina from the left psoas muscle before encroaching on the whole spinal canal and subsequently invading the contralateral neural foramina from T12 to L3. CASE REPORT: A 43-year-old man with HGBL who could function independently presented with numbness and weakness of the left thigh 2 months after a diagnosis of infiltrative lymphoma in the left psoas muscle. His symptoms were urine incontinence and unsteady gait. A neurological examination revealed weakness in the left psoas and quadriceps with hyporeflexia and hypesthesia. Lumbar spine magnetic resonance imaging (MRI) revealed intraspinal extradural invasion from T12 to L3 with multiple left-sided root compression despite the resolution of primary psoas lymphoma. At 6 weeks after symptom onset, his symptoms progressed to weakness, numbness, and hyporeflexia of the bilateral lower extremities with preserved anal sensation. Follow- up MRI revealed the progression of intraspinal invasion, which spread through the spinal canal and invaded the contralateral neural foramina from T12 to L3. The patient was finally bound to a wheelchair. CONCLUSION: Clinicians must check for possible intraspinal involvement in patients with HGBL, particularly patients with known paraspinal soft-tissue involvement. The resolved infiltration of the soft tissue does not preclude the possibility of further neurological involvement. Additionally, MRI may provide higher resolution findings for clarifying the structure of the neural foramina and thecal sac. Keyword: Non-Hodgkin's Lymphoma, high-grade B-cell lymphoma, plexopathy.

Signs and symptoms of human T-lymphotropic virus 1 and 2 infections in paediatric patients.

OBJECTIVE: To determine the prevalence of signs and symptoms of HTLV-1 and 2 infection in paediatric patients. METHODS: We included cohort, case-control and descriptive observational studies that reported the prevalence of signs and symptoms of HTLV-1 and 2 infections in paediatric patients. Searches were performed in MEDLINE® (Ovid), EMBASE and LILACS from inception to the present, and we saturated information with other sources of published and unpublished literature. We decided not to perform meta-analysis according to heterogeneity. RESULTS: A total of eight studies met the inclusion criteria for qualitative analysis. No studies of HTLV-2 were found. Females predominated and there was vertical transmission in nearly 100% of cases. Infective dermatitis was a common manifestation of HTLV in paediatric patients. In addition, persistent hyperreflexia, clonus and the Babinski sign were early neurological alterations observed in patients carrying the virus. CONCLUSION: HTLV screening is recommended in patients presenting infective dermatitis, persistent hyperreflexia, walking disturbances and in those who come from endemic zones.

Thoracic Schwannoma as an Unusual Cause of Sciatic Pain in the Chiropractic Office: A Case Report.

BACKGROUND Sciatica, which is pain radiating along the sciatic nerve distribution, is most often caused by degenerative conditions of the lower back and rarely results from lesions of the spinal cord. This case report illustrates a patient with suspected lumbar radiculopathy, ultimately diagnosed with a thoracic schwannoma after visiting a chiropractor. CASE REPORT A 61-year-old woman presented to a chiropractor with progressively worsening lower back pain radiating to the right lower extremity and unsteady gait. Her symptoms began 10 years previously and she had been diagnosed by an orthopedist with lumbar disc herniation causing radiculopathy via magnetic resonance imaging (MRI) and was treated with physical therapy and diclofenac. Upon examination by the chiropractor, the patient had bilateral lower-extremity neurologic deficits, hyperreflexia, and upgoing Babinski responses. The chiropractor ordered thoracic MRI, but the patient preferred to initiate a trial of care, which was unsuccessful. After a delay imposed by cardiac bypass surgery, the patient returned to the chiropractor with worsened symptoms and underwent thoracic MRI, revealing an intraspinal mass at T9. The patient underwent laminectomy and tumor removal, with histopathology confirming a diagnosis of schwannoma. The patient gradually improved after surgery with the help of rehabilitative exercises. CONCLUSIONS Clinicians should suspect a spinal cord lesion as a cause of sciatic pain when patients fail to improve with treatment, have a broad sensorimotor distribution unexplained by lumbar imaging findings, hyperreflexia/pathological reflexes, or other atypical findings (eg, negative neural tension tests). In such cases, MRI of the cervical and thoracic spine may be indicated.

Intraoperative bulbocavernosus reflex monitoring in posterior lumbar fusion surgery.

OBJECTIVE: To assess the utility of intraoperative bulbocavernosus reflex (BCR) monitoring in posterior lumbar fusion surgery. METHODS: We retrospectively evaluated 153 patients undergoing posterior lumbar fusion with intraoperative BCR monitoring. Voiding function was assessed at discharge and two follow-ups. RESULTS: BCR was preserved in 151 patients and completely disappeared in two patients at the end of surgery. For patients in whom BCR was preserved, voiding difficulties at discharge and 1-month and 6-month follow-ups were noted in 16 (10.6%), 9 (6.0%), and 0 (0.0%) patients, respectively. However, patients with BCR loss experienced voiding difficulties at all three time-points. Statistical analysis showed a significant difference in voiding between those with preserved and disappeared BCRs at 6 months postoperatively. BCR disappeared during surgery but recovered before the end of surgery in six patients. Among these patients, one experienced transient voiding difficulties postoperatively but with good recovery. However, the other five patients did not experience postoperative voiding difficulties. CONCLUSIONS: BCR had low sensitivity for voiding dysfunction at discharge, but had high accuracy at 6-month follow-up examinations. BCR loss was associated with new voiding dysfunction. SIGNIFICANCE: Intraoperative BCR monitoring is a potentially useful tool for enhancing safety during posterior lumbar fusion by predicting postoperative voiding dysfunction.

Cerebrospinal Fluid Interleukin-6 in Immune Checkpoint Inhibitor-Induced Autoimmune Meningoencephalitis.

Immune checkpoint inhibitors (ICIs) have proven clinical benefits in various advanced cancers. However, despite their significant therapeutic efficacy, ICIs induce immune-related adverse events. Among these events, autoimmune meningoencephalitis often has severe effects on patients' outcomes, but its specific clinical features are still unclear. Here, we report two cases of ICI-associated meningoencephalitis with elevated interleukin-6 (IL-6) levels in the cerebrospinal fluid (CSF). A 47-year-old woman (Case 1) with renal cell carcinoma developed severe headache after a seventh nivolumab administration. A neurological examination revealed jolt accentuation signs and hyperreflexia in all extremities. CSF analysis revealed a high IL-6 value (6,620 pg/mL) with marked pleocytosis. A 70-year-old woman (Case 2) who received an initial administration of nivolumab plus ipilimumab for renal cell carcinoma developed alterations of consciousness. She presented with impaired consciousness, neck stiffness, and hyperreflexia in all extremities. CSF analysis demonstrated a high IL-6 value (49.3 pg/mL) with mild pleocytosis. Both patients were treated with steroid pulse therapy (methylprednisolone 1,000 mg/day, 3 days), followed by the administration of oral predonisolone. The symptoms and laboratory findings improved in both cases. CSF IL-6 values were proportional to the severity of meningoencephalitis and other clinical parameters. These findings may help elucidate the mechanisms of central nervous system complications that are caused by ICIs.

Transconjunctival botulinum toxin injection into the lacrimal gland in crocodile tears syndrome.

Purpose: To determine the efficacy and safety of botulinum toxin injection into the lacrimal gland as a symptomatic treatment of crocodile tear syndrome (CTS). Methods: Our study included six patients of unilateral gustatory hyper lacrimation following either an episode of facial paralysis or post trauma or any related surgery that posed a risk of damaging the facial nerve. Detailed history regarding previous trauma, duration of facial paralysis, previous significant surgery, and duration of steroid use following facial paralysis was noted. Schirmer's test was done at baseline and 3 months follow-up. Patients' consent was taken prior to treatment with botulinum toxin injection in the lacrimal gland. Repeat injection of 5 U botulinum toxin (type A) was administered into the lacrimal gland of all patients transconjunctivally within an interval of 1 week. All patients were followed up with Schirmer's test at 6 weeks and 3 months. Any complications during treatment were recorded. Results: All six patients showed complete or partial disappearance of reflex lacrimation while chewing following botulinum injection measured by a significant reduction in Schirmer's value. When comparing Schirmer test values before (27.8 ± 3.58 mm) and after (11.6 ± 2.28 mm) BTX-A injection, the differences observed (P = 0.002) were statistically significant (P < 0.05). Only two patients developed mild transitory ptosis. No other complications were noted. Conclusion: Transconjunctival botulinum toxin injection into the lacrimal gland is an effective and safe method to decrease reflex lacrimation during eating or chewing in CTS or gustatory hyper-lacrimation syndrome.

Long-term surgical outcomes of levator resection in patients with Marcus-Gunn jaw-winking ptosis.

PURPOSE: To report long-term surgical outcomes of a series of MGJWS patients with moderate ptosis who underwent levator resection. MATERIALS AND METHODS: A retrospective review of medical records of 10 MGJWS patients with moderate ptosis who underwent levator resection was performed in two major eye centers in Riyadh, Saudi Arabia from January 1987 to December 2019. Clinical features, pre-operative and post-operative data of the 10 patients were recorded. OUTCOME MEASURES: Long-term upper eyelid position. RESULTS: The mean patient age at presentation was 5.4 years. Seven patients were female and three were male. All patients had moderate ptosis with marginal reflex distance ranged from 1 to 2 mm. The mean age at surgery was 9.5 years. After initial good ptosis correction for all patients, seven of them had a recurrence of ptosis several months after levator resection. CONCLUSIONS: Levator resection in MGJWS patients with moderate ptosis and good levator function is associated with a high rate of ptosis recurrence and less predictable surgical results.

Alto porcentaje de ausencia de reflejo bulbocavernoso en pacientes neurológicamente sanos con disfunción vesical / High Percentage of Absence of Bulbocavernosus Reflex in Neurologically-Healthy Patients with Bladder Dysfunction

Introducción y Objetivo El reflejo bulbocavernoso (RBCV) se ha observado ausente incluso en pacientes neurológicamente sanos. Los trastornos funcionales del piso pélvico deben incluir su evaluación. Nuestro objetivo primario fue evaluar la prevalencia de ausencia de RBCV en pacientes sanos. El objetivo secundario fue observar la afectación del RBCV en presencia de otras comorbilidades cómo enfermedad neurológica y diabetes mellitus tipo 2. Métodos Estudio descriptivo y retrospectivo, en el que se revisaron mil expedientes clínicos de pacientes sometidos a estudio urodinámico a quienes se les realizó exploración mecánica del RBCV como parte de una exploración rutinaria. Se realizó estadística descriptiva para las variables cuantitativas y cualitativas utilizando la prueba tde Student y la de chi cuadrado, respectivamente. Se consideraron estadísticamente significativos valores de p < 0,05. Resultados La muestra tenía una media de edad de 59,84 años (desviación estándar [DE]: ± 14,13 años), y contenía 36,19% de mujeres y 21,13% de hombres sin enfermedad neurológica y RBCV ausente. Se observó mayor ausencia de RBCV en pacientes con presencia de enfermedad neurológica en comparación con pacientes neurológicamente sanos: 21,6% versus 10,6%, respectivamente (p < 0,0001); además, se observó una ausencia importante de RBCV en presencia de diabetes mellitus en comparación con pacientes no diabéticos: 30.8% versus 18.8%, respectivamente (p < 0,0001). No se observaron diferencias al comparar grupos con respecto a disfunción vesical. Conclusión La ausencia de RBCV no es exclusiva de una enfermedad neurológica con repercusión de síntomas del tracto urinario inferior, y la proporción de pacientes neurológicamente sanos con ausencia de RBCV no es despreciable. No se encontró una diferencia significativa en los grupos con ausencia de RBCV con respecto a disfunción vesical.

Introduction and Objective Absence of the bulbocavernosus reflex (BCVR) has been observed even in neurologically-healthy subjects. Functional disorders of the pelvic floor should include its assessment. The primary objective of the present study was to evaluate the absence of BCVR in healthy subjects. The secondary objective was to evaluate the BCVR with regards to the presence of other comorbidities, such as neurogenic bladder and type-2 diabetes mellitus. Methods A descriptive and retrospective study in which we reviewed the clinical files of one thousand subjects who underwent a urodynamic study and were submitted to a mechanical exploration of the BCVR as part of a routine evaluation. Descriptive statistics were performed for the quantitative and qualitative variables using the Student t and the Chi-squared tests accordingly. Values of p < 0.05 was considered statistically significant. Results The sample had a mean age of 59.84 years (standard deviation [SD] ± 14.13 years), and it contained 36.19% of women and 21.13% of men without neurological disease and absent BCVR. A higher proportion of BCVR absence was observed in patients with neurological disease compared to their healthy counterparts: 21.6% and 10.6% respectively (p ≤ 0.0001); furthermore, an important absence of the BCVR was observed in patients with type-2 diabetes mellitus compared to non-diabetic patients: 30.8% and 18.8% respectively (p ≤ 0.0001). No statistically significant differences were observed in the group comparison regarding bladder dysfunction. Conclusion The absence of the RBCV is not exclusive to a neurological disease with repercussions in terms of lower urinary tract symptoms, and the proportion of neurologically healthy subjects with absence of the BCVR is not negligible. No significant difference was found in groups with absence of the BCVR with regards to bladder dysfunction

Voltage-gated potassium channel dysfunction in dorsal root ganglia contributes to the exaggerated exercise pressor reflex in rats with chronic heart failure.

An exaggerated exercise pressor reflex (EPR) causes excessive sympathoexcitation and exercise intolerance during physical activity in the chronic heart failure (CHF) state. Muscle afferent sensitization contributes to the genesis of the exaggerated EPR in CHF. However, the cellular mechanisms underlying muscle afferent sensitization in CHF remain unclear. Considering that voltage-gated potassium (Kv) channels critically regulate afferent neuronal excitability, we examined the potential role of Kv channels in mediating the sensitized EPR in male rats with CHF. Real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting experiments demonstrate that both mRNA and protein expressions of multiple Kv channel isoforms (Kv1.4, Kv3.4, Kv4.2, and Kv4.3) were downregulated in lumbar dorsal root ganglions (DRGs) of CHF rats compared with sham rats. Immunofluorescence data demonstrate significant decreased Kv channel staining in both NF200-positive and IB4-positive lumbar DRG neurons in CHF rats compared with sham rats. Data from patch-clamp experiments demonstrate that the total Kv current, especially IA, was dramatically decreased in medium-sized IB4-negative muscle afferent neurons (a subpopulation containing mostly Aδ neurons) from CHF rats compared with sham rats, indicating a potential functional loss of Kv channels in muscle afferent Aδ neurons. In in vivo experiments, adenoviral overexpression of Kv4.3 in lumbar DRGs for 1 wk attenuated the exaggerated EPR induced by muscle static contraction and the mechanoreflex by passive stretch without affecting the blunted cardiovascular response to hindlimb arterial injection of capsaicin in CHF rats. These data suggest that Kv channel dysfunction in DRGs plays a critical role in mediating the exaggerated EPR and muscle afferent sensitization in CHF.NEW & NOTEWORTHY The primary finding of this manuscript is that voltage-gated potassium (Kv) channel dysfunction in DRGs plays a critical role in mediating the exaggerated EPR and muscle afferent sensitization in chronic heart failure (CHF). We propose that manipulation of Kv channels in DRG neurons could be considered as a potential new approach to reduce the exaggerated sympathoexcitation and to improve exercise intolerance in CHF, which can ultimately facilitate an improved quality of life and reduce mortality.

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.

Hyperreflexia and enhanced ripple oscillations in the taurine-deficient mice.

In this study, we examined neuronal excitability and skeletal muscle physiology and histology in homozygous knockout mice lacking cysteine sulfonic acid decarboxylase (CSAD-KO). Neuronal excitability was measured by intracerebral recording from the prefrontal cortex. Skeletal muscle response was measured through stretch reflex in the ankle muscles. Specifically, we measured the muscle tension, amplitude of electromyogram and velocity of muscle response. Stretch reflex responses were evoked using a specialized stretching device designed for mice. The triceps surae muscle was stretched at various speeds ranging from 18 to 18,000° s-1. A transducer recorded the muscle resistance at each velocity and the corresponding EMG. We also measured the same parameter in anesthetized mice. We found that at each velocity, the CSAD-KO mice generated more tension and exhibited higher EMG responses. To evaluate if the enhanced response was due to neuronal excitability or changes in the passive properties of muscles, we anesthetize mice to eliminate the central component of the reflex. Under these conditions, CSAD-KO mice still exhibited an enhanced stretch reflex response, indicating ultrastructural alterations in muscle histology. Consistent with this, we found that sarcomeres from CSAD-KO muscles were shorter and thinner when compared to control sarcomeres. Neuronal excitability was further investigated using intracerebral recordings of brain waves from the prefrontal cortex. We found that extracellular field potentials in CSAD-KO mice were characterized by reduced amplitude of low-frequency brain waves (delta, theta, alpha, beta and gamma) and increased in the high low-frequency brain waves (slow and fast ripples). Increased slow and fast ripple rates serve as a biomarker of epileptogenic brain. We have previously shown that taurine interacts with GABAA receptors and induces biochemical changes in the GABAergic system. We suggest that taurine deficiency leads to alterations in the GABAergic system that contribute to the enhanced stretch reflex in CSAD-KO mice through biochemical mechanisms that involve alterations not only at the spinal level but also at the cortical level.

Classically Described, Paradoxically Underrecognized: A Case of Proximal Weakness, Hyporeflexia/Areflexia, and Dysautonomia.

ABSTRACT: We present a case of chronic, progressive proximal weakness with dysautonomia and hyporeflexia/areflexia ultimately diagnosed with Lambert-Eaton myasthenic syndrome. An approach to neuroanatomical localization is discussed leading to the appropriate selection of electrodiagnostic studies. The electrophysiologic triad of Lambert-Eaton myasthenic syndrome is demonstrated with diffusely reduced motor amplitudes, decrement with low-frequency repetitive nerve stimulation, and increment of motor amplitudes after maximum voluntary contraction. Subsequent serologic testing for P/Q-type voltage-gated calcium channel antibodies are markedly elevated. We highlight the clinical features and pitfalls of examining a patient with Lambert-Eaton myasthenic syndrome when suspecting this challenging diagnosis. The neurophysiological underpinning of the electrodiagnostic results is explained, and the diagnostic utility of single-fiber electromyography is briefly discussed.

Prognostic Analysis of Emergency Decompressive Craniectomy for Patients with Severe Traumatic Brain Injury with Bilateral Fixed Dilated Pupils.

OBJECTIVE: For patients with severe traumatic brain injury (sTBI) with bilateral fixed dilated pupils (BFDP), the value of aggressively decompressive craniectomy (DC) treatment is still controversial. The objective of this study was to analyze and validate the outcome of DC in patients with sTBI with BFDP. METHODS: We retrospectively collected data from 44 patients with sTBI with BFDP who underwent DC treatment from July 2011 to June 2018. Outcomes used as indicators were mortality and favorable outcome. The analysis was based on the Glasgow Outcome Scale score recorded at discharge, 6, and 12 months after trauma. RESULTS: The overall survival was 36.4% (16/44) at discharge and 25.0% (11/44) at 6 and 12 months, and the favorable outcome (Glasgow Outcome Scale score = 4-5) at discharge, 6, and 12 months after injury was 9.1% (4/44), 13.6% (6/44), and 20.5% (9/44), respectively. Sex (P = 0.046), preoperative Glasgow Coma Scale (GCS) score (P = 0.031), injury-surgery intervals (P = 0.022), and tracheotomy (P = 0.017) were independent associations to 6 and 12 months follow-up survival, whereas only preoperative GCS score (odds ratio, 6.088; confidence interval, 1.172-31.612; P = 0.032) and injury-surgery intervals (odds ratio, 0.241; confidence interval, 0.065-0.893; P = 0.033) were independent associations with 12 months follow-up favorable outcome. CONCLUSIONS: BFDP indicates a grave prognostic sign after sTBI, but the higher preoperative GCS score and shorter injury-surgery intervals in patients who underwent DC treatment might independently predict favorable outcome for patients with sTBI with BFDP, and patients might benefit more than expected if the DC treatment were applied more aggressively and positively.

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.

A movement disorder specialist gets a taste of his own medicine.

We present a case in which a movement disorder neurologist developed two different hyperkinetic movements due to corticospinal tract hyperexcitability, which resolved completely with surgical removal of an epidural spinal canal tumor. The first-hand description of these movements creates a unique opportunity for enhanced insight into these complex movement phenomena.