RESUMO
Here, we introduce the Tabulae Paralytica-a compilation of four atlases of spinal cord injury (SCI) comprising a single-nucleus transcriptome atlas of half a million cells, a multiome atlas pairing transcriptomic and epigenomic measurements within the same nuclei, and two spatial transcriptomic atlases of the injured spinal cord spanning four spatial and temporal dimensions. We integrated these atlases into a common framework to dissect the molecular logic that governs the responses to injury within the spinal cord1. The Tabulae Paralytica uncovered new biological principles that dictate the consequences of SCI, including conserved and divergent neuronal responses to injury; the priming of specific neuronal subpopulations to upregulate circuit-reorganizing programs after injury; an inverse relationship between neuronal stress responses and the activation of circuit reorganization programs; the necessity of re-establishing a tripartite neuroprotective barrier between immune-privileged and extra-neural environments after SCI and a failure to form this barrier in old mice. We leveraged the Tabulae Paralytica to develop a rejuvenative gene therapy that re-established this tripartite barrier, and restored the natural recovery of walking after paralysis in old mice. The Tabulae Paralytica provides a window into the pathobiology of SCI, while establishing a framework for integrating multimodal, genome-scale measurements in four dimensions to study biology and medicine.
Assuntos
Núcleo Celular , Epigenômica , Multiômica , Neurônios , Análise de Célula Única , Traumatismos da Medula Espinal , Transcriptoma , Animais , Feminino , Masculino , Camundongos , Atlas como Assunto , Núcleo Celular/metabolismo , Neurônios/patologia , Neurônios/metabolismo , Paralisia/genética , Paralisia/patologia , Paralisia/reabilitação , Paralisia/terapia , Recuperação de Função Fisiológica , Medula Espinal/patologia , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/reabilitação , Traumatismos da Medula Espinal/terapia , Caminhada , Anatomia Artística , Vias Neurais , Terapia GenéticaRESUMO
Melanocytomas arising from the leptomeningeal melanocytes within the central nervous system are a rare occurrence, accounting for 0.06%-0.1% of brain tumors and having an incidence of 1/10 million people per year.1-14 Here, we describe the case of 68-year-old male presenting with bilateral lower extremity weakness progressing to paralysis and urinary incontinence (Video 1). Upon examination, this gentleman had no sensation below T11. Magnetic resonance imaging showed multiple contrast-enhancing lesions with a major intradural lesion at level T11 arising from the ventrolateral surface and causing severe spinal cord compression. The multifocal nature of this tumor further adds to its rarity. Interdisciplinary indication for surgical resection of the intradural lesion was made. This was accomplished through a T11 laminectomy and concomitant T11-12 stabilization with neuromonitoring. Pathologic analysis of the resected tumor identified an S100+, HMB45+, pigmented melanocytoma. No complications occurred during the procedure. The patient was discharged to rehabilitation with persistent neurologic deficits. Routine follow-up is indicated given the high rates of recurrence and the multiple remaining tumor nodules.14.
Assuntos
Neoplasias Encefálicas , Neoplasias da Medula Espinal , Masculino , Humanos , Idoso , Melanócitos/patologia , Imageamento por Ressonância Magnética , Laminectomia , Neoplasias Encefálicas/cirurgia , Paralisia/patologia , Neoplasias da Medula Espinal/complicações , Neoplasias da Medula Espinal/diagnóstico por imagem , Neoplasias da Medula Espinal/cirurgiaRESUMO
Pronator syndrome is a median nerve entrapment neuropathy that can be difficult to diagnose due to its variable presentation and objective findings. Neurolymphomatosis is an uncommon disease in which malignant lymphocytes infiltrate central or peripheral nerve endoneurium and is often missed for prolonged periods prior to diagnosis. We present a rare case of pronator syndrome and anterior interosseous nerve palsy due to neurolymphomatosis that was occult on initial MRI in spite of the presence of a median nerve mass discovered intra-operatively during neurolysis. This case demonstrates the value of ultrasound for the examination of peripheral nerve pathology and illustrates its utility as an adjunct to MRI, in part due to the ability to screen a large region.
Assuntos
Neuropatia Mediana , Síndromes de Compressão Nervosa , Neurolinfomatose , Humanos , Neuropatia Mediana/complicações , Neuropatia Mediana/diagnóstico , Neuropatia Mediana/patologia , Nervo Mediano/patologia , Antebraço/inervação , Paralisia/complicações , Paralisia/patologia , Síndromes de Compressão Nervosa/cirurgiaRESUMO
PURPOSE: Warthin tumors (WT) are the second most common benign parotid gland neoplasms. They can occur as synchronous or metachronous lesions in 6-10% of cases. This study aims to compare the complication rate in 224 patients who underwent extracapsular dissection (ECD) or superficial parotidectomy (SP) for the treatment of a WT. METHODS: This retrospective study was conducted at the Department of Maxillo-Facial Surgery at the University of Naples "Federico II" from February 2002 to December 2018 on a group of patients who underwent surgical treatment for WT. The type of surgical technique was chosen based on Quer's classification. The complications evaluated were facial nerve palsy, hematoma, Frey's syndrome, and bleeding. RESULTS: A total of 224 patients treated from 2002 to 2018 for Warthin tumor were included in the study. Two hundred elven had solitary tumors (94.1%) and 13 had multicentric lesions (5.8%), of which 9 cases presented synchronous lesions and 4 cases presented metachronous lesions. Extracapsular dissection (ECD) was performed in 130 patients (58.3% of cases) and superficial parotidectomy (SP) in the other 94 (41.7% of cases). CONCLUSIONS: We consider both surgical techniques as valid. In our opinion, it is essential to study each case based on Quer's Classification to obtain the best surgical outcome. Based on a lower observed rate of complications such as facial nerve palsy, Frey's syndrome, and bleeding, ECD seems to be the best option for the surgical treatment of Quer Class I lesions.
Assuntos
Adenolinfoma , Neoplasias Parotídeas , Sudorese Gustativa , Humanos , Estudos Retrospectivos , Seguimentos , Adenolinfoma/cirurgia , Adenolinfoma/complicações , Adenolinfoma/patologia , Sudorese Gustativa/etiologia , Sudorese Gustativa/patologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Neoplasias Parotídeas/cirurgia , Neoplasias Parotídeas/patologia , Paralisia/complicações , Paralisia/patologia , Glândula Parótida/patologiaRESUMO
Amyotrophic lateral sclerosis (ALS) is a fatal condition characterized by the selective loss of motor neurons in the motor cortex, brainstem, and spinal cord. Muscle involvement, muscle atrophy, and subsequent paralysis are among the main features of this disease, which is defined as a neuromuscular disorder. ALS is a persistently progressive disease, and as motor neurons continue to degenerate, individuals with ALS experience a gradual decline in their ability to perform daily activities. Ultimately, muscle function loss may result in paralysis, presenting significant challenges in mobility, communication, and self-care. While the majority of ALS research has traditionally focused on pathogenic pathways in the central nervous system, there has been a great interest in muscle research. These studies were carried out on patients and animal models in order to better understand the molecular mechanisms involved and to develop therapies aimed at improving muscle function. This review summarizes the features of ALS and discusses the role of muscle, as well as examines recent studies in the development of treatments.
Assuntos
Esclerose Lateral Amiotrófica , Animais , Humanos , Esclerose Lateral Amiotrófica/terapia , Esclerose Lateral Amiotrófica/patologia , Neurônios Motores/metabolismo , Músculo Esquelético/patologia , Atrofia Muscular/metabolismo , Paralisia/complicações , Paralisia/patologiaRESUMO
BACKGROUND: Because the robotic arm is located on the dorsal side of the patient, when the esophagus is pulled dorsally for the left recurrent nerve lymph node (LRLN) dissection, the robotic arm interferes with the surgical field. This made it difficult to prepare for the left recurrent lymph node dissection. We developed LRLN dissection in robotic surgery with natural space creation by physiological organ movement and evaluated the short-term results. METHODS: In this retrospective study, we analyzed 102 cases of robot-assisted thoracoscopic subtotal esophagectomy (RATE) among radical subtotal esophagectomies performed between December 2018 and December 2022 using medical records. LRLN dissection is preceded by a dissection of the esophagus from the trachea. Leaving the esophagus on the vertebral side and away from the trachea resulted in a physiological elevation of the esophagus, providing space between the trachea and esophagus. RESULTS: The thoracic surgery time in RATE was 181 (115-394) min. The number of LRLNs dissected was 4 (1-14). Six patients (6%) had a postoperative recurrence in the mediastinal lymph nodes. Seven patients (7%) had grade ≥ 1 left recurrent nerve palsy. CONCLUSIONS: LRLN dissection with RATE using natural space creation was performed safely with a sufficient number of dissected lymph nodes and little left recurrent nerve palsy.
Assuntos
Neoplasias Esofágicas , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Esofagectomia/efeitos adversos , Esofagectomia/métodos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Estudos Retrospectivos , Tração , Excisão de Linfonodo/efeitos adversos , Excisão de Linfonodo/métodos , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Linfonodos/cirurgia , Linfonodos/patologia , Paralisia/patologia , Paralisia/cirurgiaRESUMO
BACKGROUND: The effect of lymphadenectomy around the recurrent laryngeal nerve (RLN) in open esophagectomy has been demonstrated with the efficacy index (EI). However, it remains unclear whether this effect exists for minimally invasive esophagectomy (MIE) in the prone position. The purpose of this study was to clarify whether the upper mediastinal lymphadenectomy contributed to improved prognosis in patients with esophageal squamous cell carcinoma. STUDY DESIGN: This study included 339 patients with esophageal squamous cell carcinoma treated with MIE in the prone position at Kobe University or Hyogo Cancer Center, Japan, from 2010 to 2015. EIs for each station, correlations between metastatic lymph nodes around the left RLN and RLN palsy, and survival of patients with and without upper mediastinal lymphadenectomy were investigated. RESULTS: Among 297 patients treated with upper mediastinal lymphadenectomy, Clavien- Dindo grade ≥ II left RLN palsy occurred in 59 patients (20%). Overall, EIs for the right RLN (7.4) and left RLN (6.6) were higher than EIs for other stations. For patients with upper-third or middle-third tumors, the trend was stronger. Left RLN palsy was more likely in patients with metastatic lymph nodes around the left RLN than in those without (44% vs 15%, p < 0.0001). After propensity score-matching, 42 patients were included in each group with and without upper mediastinal lymphadenectomy. In survival analyses, the 5-year overall survival rates were 55% vs 35% and cause-specific survival rates were 61% vs 43% for the patients with and without upper mediastinal lymphadenectomy respectively. Significant differences were confirmed in survival curves (overall survival: p = 0.03; cause-specific survival: p = 0.04, respectively). CONCLUSIONS: Upper mediastinal lymphadenectomy contributes to improved prognosis with high EIs in MIE in the prone position.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/cirurgia , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Esofagectomia , Pontuação de Propensão , Estudos Retrospectivos , Excisão de Linfonodo , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Prognóstico , Nervo Laríngeo Recorrente/patologia , Nervo Laríngeo Recorrente/cirurgia , Paralisia/patologia , Paralisia/cirurgiaRESUMO
OBJECTIVES: To evaluate the effect of inferior oblique (IO) myectomy on ocular torsion according to the absence of the trochlear nerve in unilateral congenital superior oblique palsy (UCSOP). METHODS: We retrospectively reviewed the clinical data of patients who had been diagnosed with UCSOP and underwent ipsilateral IO myectomy (n = 43). Patients were classified into the present and absent groups according to the absence of the trochlear nerve and superior oblique hypoplasia on magnetic resonance imaging (MRI). For quantitative analysis of ocular torsion, disc-fovea angles (DFA) were collected in both eyes using fundus photographs taken within three months before surgery and one month after surgery. RESULTS: DFA of the paretic eye did not differ according to the absence of the trochlear nerve (9.4±5.6° in the present group vs. 11.0±5.4° in the absent group, p = 0.508). However, the present group had a larger DFA in the non-paretic eye than the absent group (14.1±6.7° in the present group vs. 8.0±5.0° in the absent group, p = 0.003). The change of ocular torsion after IO myectomy in the paretic eye was -5.3±3.7° in the present group and -4.8±3.5° in the absent group, respectively (p = 0.801). In the non-paretic eye, the change in DFA was -1.5±3.0° in the present group, which was larger than that in the absent group (0.7±2.6°, p = 0.047). In the multivariate analysis, the change in DFA was correlated with only the preoperative DFA (standardized ß = -0.617, p<0.001 in the paretic eye, and standardized ß = -0.517, p<0.001 in the non-paretic eye). CONCLUSIONS: In the paretic eye, there was no significant difference in the change of ocular torsion between both groups, whereas in the non-paretic eye, the present group had a larger change in DFA after IO myectomy than the absent group. However, in the multivariable analysis, the change in ocular torsion was significantly correlated with preoperative excyclotorsion but not with the presence of the trochlear nerve itself.
Assuntos
Estrabismo , Doenças do Nervo Troclear , Humanos , Nervo Troclear/cirurgia , Nervo Troclear/anormalidades , Nervo Troclear/patologia , Doenças do Nervo Troclear/cirurgia , Doenças do Nervo Troclear/congênito , Doenças do Nervo Troclear/diagnóstico , Estudos Retrospectivos , Músculos Oculomotores/patologia , Fóvea Central , Paralisia/patologia , Estrabismo/cirurgia , Estrabismo/patologiaRESUMO
Orbital myositis comprises a subtype of idiopathic orbital inflammation. Symptoms and clinical signs include orbital pain, eyelid swelling, ptosis, and conjunctival chemosis, sometimes concurrent with diplopia. Orbital myositis typically occurs in an idiopathic acute form and affects one or more extraocular muscles. It mainly involves the rectus muscles; cases involving the superior oblique muscle have been rarely reported. We report the case of a 57-year-old man with sudden-onset diplopia. Initial examination was suggestive of right superior oblique muscle palsy; however, myositis of the right superior oblique muscle was confirmed on magnetic resonance imaging (MRI). The patient was started on intravenous steroid pulse treatment. The steroid was tapered for 4 months. Diplopia, exotropia, and excyclotorsion of the right eye disappeared after 3 weeks of treatment. Cranial MRI obtained 2 months after starting treatment showed a normal superior oblique muscle. There has been no recurrence with 8 months of follow-up after completing the steroid taper.
Assuntos
Miosite , Miosite Orbital , Doenças do Nervo Troclear , Masculino , Humanos , Pessoa de Meia-Idade , Músculos Oculomotores/diagnóstico por imagem , Músculos Oculomotores/patologia , Miosite Orbital/diagnóstico , Miosite Orbital/diagnóstico por imagem , Diplopia/diagnóstico , Diplopia/tratamento farmacológico , Miosite/diagnóstico , Miosite/tratamento farmacológico , Miosite/patologia , Esteroides , Paralisia/patologiaRESUMO
OBJECTIVE: This study aimed to investigate the prognostic factors and treatment outcomes in patients with the external auditory canal (EAC) squamous cell carcinoma (SCC). METHODS: All patients diagnosed with EAC SCC and treated with curative intent at a single tertiary institution were retrospectively reviewed over a 22-year period. Treatment modalities included surgery with adjuvant treatment or definitive radiotherapy. The primary endpoints were overall survival (OS) and disease-specific survival (DSS). RESULTS: There were 51 patients in our cohort. The 5-year OS and DSS were 64.0% ± 7.0% and 72.0% ± 7.0% respectively. Patients in the surgical arm and RT arm showed no significant difference in OS, DSS, and LRFS (p = 0.075, 0.062, 0.058 respectively). Compared to other routes of spread within the temporal bone, pattern of posterior disease invasion (involving mastoid/sigmoid sinus) showed poorer OS and DSS on multivariate analysis (hazard ratio, HR4.34 and 5.88; p = 0.006 and 0.009). On multivariate analysis, the following factors were independently prognostic of poorer OS and DSS: Previous radiotherapy (HR 3.29 and 4.81, p = 0.021 and p = 0.029); Presence of facial nerve palsy (HR 3.80 and 7.63, p = 0.013 and p = 0.003); Posterior pattern of invasion (HR4.05 and 3.59, p = 0.013 and p = 0.043). Advanced modified Pittsburgh stage was not predictive of poor OS and DSS (HR1.17 and 1.17 E+5, p = 0.786 and p = 0.961). CONCLUSION: Presence of previous radiotherapy, facial nerve palsy and posterior pattern of disease invasion were independent prognostic factors of poorer survival in patients with EAC SCC. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2203-2210, 2023.
Assuntos
Carcinoma de Células Escamosas , Meato Acústico Externo , Humanos , Prognóstico , Estudos Retrospectivos , Meato Acústico Externo/cirurgia , Estadiamento de Neoplasias , Carcinoma de Células Escamosas/patologia , Paralisia/patologiaRESUMO
Spinal cord injury (SCI), a debilitating medical condition that can cause irreversible loss of neurons and permanent paralysis, currently has no cure. However, regenerative medicine may offer a promising treatment. Given that numerous regenerative strategies aim to deliver cells and materials in the form of tissue-engineered therapies, understanding and characterising the mechanical properties of the spinal cord tissue is very important. In this study, we have systematically characterised the spatiotemporal changes in elastic stiffness (elastic modulus, Pa) and viscosity (drop in peak force, %) of injured rat thoracic spinal cord tissues at distinct time points after crush injury using the indentation technique. Our results demonstrate that in comparison with uninjured spinal cord tissue, the injured tissues exhibited lower stiffness (median 3281 Pa versus 9632 Pa; P < 0.001) but demonstrated elevated viscosity (median 80% versus 57%; P < 0.001) at 3 days postinjury. Between 4 and 6 weeks after SCI, the overall viscoelastic properties of injured tissues returned to baseline values. At 12 weeks after SCI, in comparison with uninjured tissue, the injured spinal cord tissues displayed a significant increase in both elasticity (median 13698 Pa versus 9920 Pa; P < 0.001) and viscosity (median 64% versus 58%; P < 0.001). This work constitutes the first quantitative mapping of spatiotemporal changes in spinal cord tissue elasticity and viscosity in injured rats, providing a mechanical basis of the tissue for future studies on the development of biomaterials for SCI repair. STATEMENT OF SIGNIFICANCE: Spinal cord injury (SCI) is a devastating disease often leading to permanent paralysis. While enormous progress in understanding the molecular pathomechanisms of SCI has been made, the mechanical properties of injured spinal cord tissue have received considerably less attention. This study provides systematic characterization of the biomechanical evolution of rat spinal cord tissue after SCI using a microindentation test method. We find spinal cord tissue behaves significantly softer but more viscous immediately postinjury. As time passes, the lesion site gradually returns to baseline values and then displays pronounced increased viscoelastic properties. As host tissue mechanical properties are a crucial consideration for any biomaterial implanted into central nervous system, our results may have important implications for further studies of SCI repair.
Assuntos
Traumatismos da Medula Espinal , Ratos , Animais , Traumatismos da Medula Espinal/terapia , Traumatismos da Medula Espinal/patologia , Medula Espinal/patologia , Elasticidade , Fenômenos Mecânicos , Paralisia/patologiaRESUMO
Purpose: Although the three-step test (3ST) is typically used to diagnose superior oblique palsy (SOP), sagging eye syndrome (SES) has clinical similarities. We sought to determine if alignment measurements can distinguish unilateral SOP from hypertropia in SES. Methods: We studied hypertropic subjects who underwent surface-coil magnetic resonance imaging (MRI) demonstrating either SO cross-section reduction indicative of congenital or acquired palsy (SOP group) or lateral rectus muscle sag (SES group). Alignment was measured by Hess screen and prism-cover testing. Multiple supervised machine learning methods were employed to evaluate diagnostic accuracy. Rectus pulley coordinates were determined in SES cases fulfilling the 3ST. Results: Twenty-three subjects had unilateral SOP manifested by SO atrophy. Eighteen others had normal SO size but MRI findings of SES. Maximum cross-section of the palsied SO was much smaller than contralaterally and in SES (P < 2 × 10-5). Inferior oblique cross-sections were similar in SOP and SES. In both SOP and SES, hypertropia increased in contralateral and decreased in ipsilateral gaze and was greater in ipsilateral than contralateral head tilt. In SES, nine subjects (50%) fulfilled the 3ST and had greater infraplacement of the lateral than medial rectus pulleys in the hypotropic orbit. Supervised machine learning of alignment data distinguished the diagnoses with areas under the receiver operating curves up to 0.93, representing excellent yet imperfect differential diagnosis. Conclusions: Because the 3ST is often positive in SES, clinical alignment patterns may confound SES with unilateral SOP, particularly acquired SOP. Machine learning substantially but imperfectly improves classification accuracy.
Assuntos
Estrabismo , Doenças do Nervo Troclear , Humanos , Músculos Oculomotores/patologia , Órbita , Paralisia/complicações , Paralisia/patologia , Estudos Retrospectivos , Estrabismo/diagnóstico , Estrabismo/patologia , Síndrome , Doenças do Nervo Troclear/complicações , Doenças do Nervo Troclear/diagnósticoRESUMO
Objective: To investigate the feasibility and advantages of Fang's capillary fascia preservation right recurrent laryngeal nerve (RLN) dissection technique (F-R-RLN dissection) with preservation of the capillary network and fascia between the RLN and common carotid artery for greater neuroprotective efficiency compared with traditional techniques. Methods: We retrospectively analyzed 102 patients with papillary thyroid carcinoma undergoing right level VI lymph node dissection in our department from March 2021 to January 2022. Sixty patients underwent F-R-RLN dissection (the experimental group) and 42 patients underwent standard dissection (the control group). The intraoperative electrical signal amplitude ratios of the RLN, the number of dissected lymph nodes, and the preservation rates of the parathyroid glands were recorded and compared between the two groups. Results: The electrical signal amplitude ratio of the lower neck part point of the RLN to the upper laryngeal inlet point in the experimental group was significantly lower than the ratio in the control group (p = 0.006, Z-score = -2.726). One patient suffered transient RLN paralysis in both groups, but this resolved within 1 month after operation. There were no significant differences between the two groups in terms of the number of level VIa or level VIb lymph nodes dissected, nor in the rate of preservation of the parathyroid glands. Conclusions: F-R-RLN dissection is a thorough dissection technique that is effective at preventing an electrical signal amplitude decrease in the RLN, and at preventing RLN paralysis by preserving its blood supply.
Assuntos
Fármacos Neuroprotetores , Neoplasias da Glândula Tireoide , Fáscia/patologia , Humanos , Paralisia/patologia , Nervo Laríngeo Recorrente/patologia , Nervo Laríngeo Recorrente/cirurgia , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgiaRESUMO
The D620N mutation in vacuolar protein sorting protein 35 (VPS35) gene has been identified to be linked to late onset familial Parkinson disease (PD). However, the pathophysiological roles of VPS35-D620N in PD remain unclear. Here, we generated the transgenic Caenorhabditis elegans overexpressing either human wild type or PD-linked mutant VPS35-D620N in neurons. C. elegans expressing VPS35-D620N, compared with non-transgenic controls, showed movement disorders and dopaminergic neuron loss. VPS35-D620N worms displayed more swimming induced paralysis but showed no defects in BSR assays, thus indicating the disruption of dopamine (DA) recycling back inside neurons. Moreover, VPS35 formed a protein interaction complex with DA transporter (DAT), RAB5, RAB11 and FAM21. In contrast, the VPS35-D620N mutant destabilized these interactions, thus disrupting DAT transport from early endosomes to recycling endosomes, and decreasing DAT at the cell surface. These effects together increased DA in synaptic clefts, and led to dopaminergic neuron degeneration and motor dysfunction. Treatment with reserpine significantly decreased the swimming induced paralysis in VPS35-D620N worms, as compared with vehicle treated VPS35-D620N worms. Our studies not only provide novel insights into the mechanisms of VPS35-D620N-induced dopaminergic neuron degeneration and motor dysfunction via disruption of DAT function and the DA signaling pathway but also indicate a potential strategy to treat VPS35-D620N-related PD and other disorders.
Assuntos
Dopamina , Doença de Parkinson , Animais , Humanos , Dopamina/metabolismo , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismo , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Transporte Proteico , Neurônios Dopaminérgicos/metabolismo , Doença de Parkinson/metabolismo , Degeneração Neural/patologia , Paralisia/genética , Paralisia/metabolismo , Paralisia/patologiaRESUMO
The rostral mesencephalon may influence ocular motility in the vertical, horizontal, and torsional trajectories through intricate supranuclear, internuclear, and infranuclear neural networks. Strategic unilateral midbrain lesions may result in contralateral horizontal gaze palsy with saccadic failure due to combined interruption of supranuclear corticofugal fibers from the frontal eye field and colliculofugal fibers from the superior colliculus. In this article, we report a patient who sustained combined vertical and horizontal gaze deficits after a single infarct involving the mesodiencephalic junction. The neural substrate for each deficit is briefly discussed in light of clinical findings. This case presented a triad of three distinct syndromes of horizontal gaze paresis, vertical one-and-a-half syndrome, and pseudoabducens palsy due to damage of nuclear and supranuclear projections within the rostral mesencephalon. This combination was due to a single embolic infarct in the territory of the posterior thalamosubthalamic artery (artery of Percheron) that arises at the basilar bifurcation. Coexistence of these phenomena exemplified how rostral midbrain lesions may affect ocular motility in the vertical, horizontal, and torsional planes, along with disruption of normal vergence control.
Assuntos
Imageamento por Ressonância Magnética , Estrabismo , Humanos , Infarto/patologia , Mesencéfalo/irrigação sanguínea , Mesencéfalo/patologia , Paralisia/patologia , Paresia , Estrabismo/patologiaRESUMO
PURPOSE: We evaluated patients with hypertropia compatible with a diagnosis of superior oblique (SO) palsy to ascertain whether the 3-step test (3ST) can distinguish SO atrophy characteristic of trochlear nerve pathology from masquerading conditions. DESIGN: Prospective cross-sectional study. METHODS: In an academic practice, we performed quasi-coronal plane, surface coil magnetic resonance imaging in 83 patients clinically diagnosed with SO palsy. We evaluated alignment, SO cross-sectional area, SO contractility, and rectus muscle pulley positions. RESULTS: A total of 57 patients with mean age 39 years (SDâ¯=â¯21 years) had unilateral SO palsy manifested by SO atrophy (22 congenital and 35 acquired). There was normal SO size in 26 patients with an average age of 39 years (SD =16 years) considered masquerades (8 congenital and 18 acquired). Maximum palsied SO cross-section averaged 9.5 ± 3.8 mm2, less than 18.4 ± 3.9 mm2 contralaterally (P < 10-24). In masquerades, maximum hypertropic SO cross-section was 20.7 ± 3.1 mm2, which was not different from the hypotropic SO or the contralesional muscle in SO palsy. Head tilt testing in masquerades was indistinguishable from SO palsy. In SO palsy, central hypertropia averaged 13.2 ± 9.4Δ, increasing to 21.1 ± 14.0Δ in ipsilateral tilt, and decreasing to 4.3 ± 5.3Δ in contralateral tilt. In masquerades, central hypertropia averaged 13.1 ± 8.7Δ, and was 17.7 ± 11.1Δ in ipsilateral and decreasing to 4.9 ± 5.1Δ in contralateral tilt. Upright hypertropia was larger at 17.7 ± 9.9Δ in congenital than 12.0 ± 8.4Δ in acquired SO palsy (Pâ¯=â¯0025) but was indistinguishable from congenital masquerades. Contractile change in SO cross-section was bilaterally similar in masquerades. Relevant coordinates of rectus pulleys were similar bilaterally in masquerades. CONCLUSIONS: The 3ST pattern characteristic of unilateral SO palsy may be mimicked in all respects by masquerades.
Assuntos
Estrabismo , Doenças do Nervo Troclear , Adulto , Atrofia , Estudos Transversais , Humanos , Músculos Oculomotores/diagnóstico por imagem , Músculos Oculomotores/patologia , Paralisia/patologia , Estudos Prospectivos , Estrabismo/diagnóstico , Doenças do Nervo Troclear/diagnósticoRESUMO
INTRODUCTION: Hereditary neuropathy with liability to pressure palsy (HNPP) is an autosomal dominant disorder, typically presenting with recurrent episodes of mononeuropathy in nerves susceptible to compression, with similar neurophysiological characteristics. However, other clinical and neurophysiological presentations have been reported. METHODS: We retrospectively analysed the clinical and neurophysiological characteristics of 20 patients with genetically confirmed HNPP. Sixteen patients were studied in our department between 1996 and 2016. RESULTS: In addition to the typical characteristics of HNPP, we found atypical forms including recurrent positional sensory symptoms in 3 patients, chronic sensorimotor polyneuropathy in one, and non-progressive mononeuropathy in one. Onset was early in 2 patients: one at the age of 7 years, with common peroneal nerve injury, and another at birth, with brachial plexus involvement. By frequency, the main pathological findings in the nerve conduction study were: decreased sensory nerve conduction velocity in the sural (84%) and the median and superficial peroneal nerves (94%); decreased motor nerve conduction velocity in the ulnar nerve through the elbow (97%), and increased motor distal latency of the median and deep peroneal nerves (74%). CONCLUSION: Our results confirm the clinical variability of HNPP, with the most frequent nerve conduction study findings being the generalised decrease in sensory nerve conduction velocity, in addition to motor involvement, mainly in locations susceptible to nerve compression. The nerve conduction study can detect typical, atypical, and asymptomatic cases of HNPP.
Assuntos
Artrogripose , Neuropatia Hereditária Motora e Sensorial , Artrogripose/genética , Criança , Deleção Cromossômica , Cromossomos , Neuropatia Hereditária Motora e Sensorial/genética , Humanos , Recém-Nascido , Paralisia/genética , Paralisia/patologia , Estudos RetrospectivosRESUMO
PURPOSE: This study evaluated the prognosis of patients with traumatic unilateral superior oblique palsy (SOP) and clinical factors associated with spontaneous resolution. METHODS: Medical records of patients with traumatic unilateral SOP who visited two hospitals (Yeungnam University Hospital and Daegu Catholic University Medical Center) between January 2015 and June 2020 were reviewed retrospectively. When traumatic unilateral SOP did not recover within at least 1 year of follow-up, no spontaneous resolution was considered. Both traumatic and ocular factors were evaluated to evaluate their association with spontaneous recovery. RESULTS: Fifty-nine patients (mean age, 52.6 years; 48 male patients) were enrolled in this study. The mean interval from trauma to initial presentation was 3.9 months. The mean vertical deviation at initial presentation was 6.34 ± 5.22 prism diopters (PD) (range, 0-25 PD). During the mean 24.1-month follow-up period, 28 patients (47.5%) achieved spontaneous resolution of SOP. Thirteen patients underwent surgical treatment for SOP. Vertical deviation <6 PD at the initial visit and low fundus torsion in the nonparetic eye and both eyes were significantly associated with spontaneous recovery (p < 0.05, logistic regression analysis). Traumatic factors, including the trauma type, presence of intracranial lesion, loss of consciousness, and Glasgow Coma Scale score, were not associated with spontaneous recovery. CONCLUSIONS: In this multicenter study, spontaneously recovery was achieved in 47.5% patients with traumatic unilateral SOP. Even mild head trauma can lead to permanent SOP. Ocular factors, including the angle of deviation and fundus torsion, may better predict spontaneous resolution than traumatic factors in patients with traumatic unilateral SOP.
Assuntos
Estrabismo , Doenças do Nervo Troclear , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Músculos Oculomotores/patologia , Músculos Oculomotores/cirurgia , Paralisia/patologia , Prognóstico , Estudos Retrospectivos , Estrabismo/cirurgia , Doenças do Nervo Troclear/diagnóstico , Doenças do Nervo Troclear/cirurgiaRESUMO
OBJECTIVE: To compare preoperative and postoperative lower cranial nerve (LCN) function between Class C1 and C2 tympanojugular paraganglioma (TJP) with/without intracranial intradural (Di)/extradural (De) extensions, according to the experience of a single surgeon over four decades. STUDY DESIGN: Retrospective review. SETTING: Quaternary referral center for otology and skull base surgery. MATERIAL AND METHODS: A chart review was conducted of all the patients operated for C1/C2 TJPs from September 1983 to December 2018. The tumors were classified as: Limited-Group (C1/C2 without Di/De extensions) and Extended-Group (C1/C2 with Di/De extensions). RESULTS: Of 159 patients, 107 (67.3%) were women; the mean age at surgery was 46.5âyears. The Limited-Group (56.6%) comprised C1 (41.1%) and C2 (58.9%) tumors; the Extended-Group (43.4%) comprised C1+Di/De (14.5%) and C2+Di/De (85.5%) tumors. The prevalence of preoperative LCN palsy was 11.9 times higher in Extended than Limited tumors: 61.9% versus 4.9% (pâ<â0.05). The risk for postoperative LCN palsy was 4.7 times greater in Extended than Limited tumors: 29.2% versus 12.9%, pâ=â0.01. CONCLUSION: Especially in younger patients, complete removal of Limited C1/C2 tumors, before they extend intracranially, reduces the risk of dysfunctionality of LCNs and the burden of residual tumor. The incidence of new tumors increased over four decades. However, new-postoperative LCN palsy did not occur in any Limited C1/C2 tumors operated after the year 2000, and declined to less than 10% of Extended C1/C2 tumors.
Assuntos
Paraganglioma , Nervos Cranianos/patologia , Nervos Cranianos/cirurgia , Feminino , Humanos , Paralisia/patologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
While most cases of superior oblique (SO) hypofunction represent contractile weakness due to denervation, sometimes the lesion is exclusively in the tendon. This study sought to distinguish the pattern of incomitant strabismus caused by deficiency of SO oculorotary force caused by tendon abnormalities versus that of neurogenic palsy. Clinical and magnetic resonance imaging (MRI) findings of 7 cases of unilateral SO tendon interruption or extirpation were compared with 11 cases of age matched unilateral SO palsy having intact tendons. We compared angles of misalignment with high-resolution MRI in central gaze and deorsumversion. Muscle bellies in neurogenic palsy were markedly atrophic with maximal cross sections averaging 6.5 ± 2.7 mm2, in contrast with 13.5 ± 3.0 mm2 contralesionally (P < .0001). In contrast, SO muscle bellies ipsilateral to tendon interruption had maximum cross sections averaging 15.1 ± 3.0 mm2 occurring more posterior than on the contralesional side whose maximum averaged 12.1 ± 2.4 mm2. While cross sections of SO bellies ipsilateral to tendon interruption exhibited normal contractile increase in infraduction (P < .0005), there was nevertheless strabismus with incomitance similar to that in SO atrophy. Binocular alignment was statistically similar (P > .5) in the two groups for all diagnostic positions, including head tilt, except in deorsumversion, where cases with SO tendon abnormalities averaged 20.5 ± 6.9Δ ipsilateral hypertropia, significantly more than 8.5 ± 6.6Δ in neurogenic SO atrophy (P = .001). The average difference in hypertropia Hypertropia averaged 9D greater in deorsumversion than central gaze in tendon abnormalities, but 4.1Δ less in SO atrophy (P< .019). In contralesional version, average overelevation in adduction was 1.7 (scale of 0-4) in tendon abnormalities, and 2.6 in SO atrophy (P = .23), while average underdepression in adduction was -2.3 in cases of tendon abnormalities and -1.6 in SO atrophy (P = .82). Repair of the SO tendon in three cases was effective, while alternative procedures were performed when repair was infeasible. While both denervation and tendon interruption impair SO oculorotary function, interruption causes greater hypertropia in infraversion. Surgical tightening of interrupted SO tendons may have particularly gratifying effects. Posterior SO thickening and large hypertropia in infraversion suggest SO tendon interruption that may guide a surgical strategy of tendon repair.