Pregnancy following Brown-Séquard syndrome: A rare case report

Brown-Séquard syndrome is an incomplete spinal cord lesion characterized by hemisection injury of the cord. We present a case of pregnancy, delivery and postpartum course following this rare neurological condition. A 42-year-old woman presented with past history of idiopathic hemicord myelitis leading to right sided hemiplegia with decreased contralateral sensation of pain and temperature, consistent with Brown-Séquard syndrome, which was treated with steroids and Therapeutic Plasma Exchange. Thereafter, she had near-complete motor recovery and complete sensory recovery over the next 3months. Three years later, she presented to us at 37+2 weeks of gestation with residual hemiparesis with motor power grade of 4/5 in right upper and lower limbs. She underwent Caesarean section for breech presentation, which was done under general anaesthesia in view of prior spinal cord lesion. She was discharged for follow-up in Neurology outpatient clinic and physical rehabilitation. At follow up after 12 months of delivery, she had complete motor and sensory recovery. Management of spinal cord lesions in pregnancy and delivery requires specialist multidisciplinary care due to risk of medical and obstetric complications. This case demonstrates a rare scenario of a primigravida at term gestation with residual deficits of a past spinal cord lesion.

Weakness With Neck Flexion

A 51-year-old woman sought care for difficulty “picking up” her right foot after walking for 30 minutes; with rest, the symptoms would subside. A few months later, she reported a “zinging” sensation in her right 4th and 5th fingers and down her right side with neck flexion. Brain magnetic resonance imaging showed tiny nonspecific lesions not suggestive of demyelinating disease and a single T2 hyperintensity at the cervicomedullary junction that did not enhance with gadolinium administration. Cerebrospinal fluid analysis showed 10 oligoclonal bands on isoelectric focusing electrophoresis and a mildly increased immunoglobulin G index of 0.73. The patient was diagnosed with solitary sclerosis, suspected to be a form of central nervous system demyelinating disease strongly related to multiple sclerosis. Treatment was based on a diagnosis of “primary progressive multiple sclerosis,” although the patient did not satisfy the criterion of dissemination in space. The patient was being treated with glatiramer acetate 40 mg 3 times weekly for a presumptive diagnosis of multiple sclerosis before evaluation at Mayo Clinic. After our evaluation, she was advised that no treatments at that time were efficacious to prevent deterioration in patients with primary progressive multiple sclerosis. The mainstay of treatment is physical medicine modalities, including principles of energy conservation and, when necessary, mobility aids, such as braces and canes. The presentation of disease in this patient suggested a chronic myelopathy. Her symptoms did not develop acutely and manifested only after she walked a distance. Symptoms involving the upper and lower extremities and precipitation of Lhermitte sign with neck flexion also suggested a spinal cord lesion, typically a demyelinating lesion. However, a single spinal cord lesion present at the cervicomedullary junction. Oligoclonal bands are detected in patients with central nervous system infections or paraneoplastic disorders that might be associated with myelopathy.

Gait Analysis Using Animal Models of Peripheral Nerve and Spinal Cord Injuries

The present review discusses recent data regarding rodent models of spinal cord and peripheral nerve injuries in terms of gait analysis using the CatWalk system (CW), an automated and exceptionally reliable system for assessing gait abnormalities and motor coordination. CW is a good tool for both studying improvements in the walking of animals after suffering a peripheral nerve and spinal cord lesion and to select the best therapies and procedures after tissue destruction, given that it provides objective and quantifiable data. Most studies using CW for gait analysis that were published in recent years focus on injuries inflicted in the peripheral nerve, spinal cord, and brain. CW has been used in the assessment of rodent motor function through high-resolution videos, whereby specialized software was used to measure several aspects of the animal’s gait, and the main characteristics of the automated system are presented here. CW was developed to assess footfall and gait changes, and it can calculate many parameters based on footprints and time. However, given the multitude of parameters, it is necessary to evaluate which are the most important under the employed experimental circumstances. By selecting appropriate animal models and evaluating peripheral nerve and spinal cord lesion regeneration using standardized methods, suggestions for new therapies can be provided, which represents the translation of this methodology into clinical application.

Indolent nonendemic central nervous system histoplasmosis presenting as an isolated intramedullary enhancing spinal cord lesion

Background: Histoplasma capsulatum infection is largely seen in endemic regions; it results in symptomatic disease in <5% of those infected and is most often a self-limiting respiratory disease. Disseminated histoplasmosis is considered rare in the immunocompetent host. Central nervous system (CNS) dissemination can result in meningitis, encephalitis, and focal lesions in the brain and spinal cord, stroke, and hydrocephalus. An intramedullary spinal cord lesion as the only manifestation of CNS histoplasmosis has been rarely described. Case Description: We present an atypical case of a 44-year-old man from a nonendemic region, on adalimumab therapy for ulcerative colitis who developed an isolated intramedullary spinal cord lesion in the setting of disseminated histoplasmosis. His course was initially indolent with vague systemic symptoms that led to consideration of several other diagnoses including sarcoidosis and lymphoma. Biopsies of several positron emission tomography positive lymph nodes revealed granulomatous inflammation, but no firm diagnosis was achieved. He was ultimately diagnosed with histoplasmosis after an acute respiratory infection in the setting of anti-tumor necrosis factor therapy. With appropriate antifungal therapy, the spinal cord lesion regressed. The previous systemic biopsies were re-reviewed, and rare fungal elements consistent with H. capsulatum were identified. A presumptive diagnosis of CNS histoplasmosis was made in the absence of direct laboratory confirmation in the setting of rapid and complete resolution on antifungal therapy. Conclusion: Disseminated histoplasmosis should be considered in granulomatous disease, even if the patient resides in a nonendemic region. Furthermore, clinicians should be mindful that CNS histoplasmosis may present in an atypical fashion.

Silent progression of brain atrophy in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder

ObjectiveTo investigate longitudinal brain atrophy in patients with neuromyelitis optica spectrum disorder (NMOSD).MethodsWe investigated the longitudinal brain atrophy rate in patients with aquaporin-4 antibody-positive NMOSD (AQP4+NMOSD) and those with multiple sclerosis (MS) in a retrospective cohort study. Brain volume was calculated with statistical parametric mapping-12.ResultsWe enrolled 36 patients with AQP4+NMOSD and 60 with MS. Patients with NMOSD were older and had a higher Kurtzke’s expanded disability status scale score at baseline MRI compared with those with MS. Disease duration, annual relapse rate and intervals from the last attack and from disease-modifying drugs initiation were not significantly different between the two groups. Lower normalised lesion volume and higher normalised white matter volume were found in patients with NMOSD compared with those with MS at baseline MRI. However, the annualised atrophy rate of normalised brain volume was similar between the NMOSD (median 0.47; IQR 0.75; p=0.49) and MS (median 0.46; IQR 0.84) groups. After adjustment of age and the presence of clinical relapse, no differences of the annualised atrophy rate of normalised brain volume also were found for NMOSD and MS. Patients with AQP4+NMOSD with long cord lesion showed higher annualised atrophy rate of normalised grey matter volume compared with those without long cord lesion.ConclusionsSilent progression of brain atrophy was present in patients with AQP4+NMOSD, as shown in patients with MS, even in the clinically inactive age-matched cases. Subclinical dying back degeneration may explain the brain atrophy in patients with AQP4 +NMOSD.

The functional properties of synapses made by regenerated axons across spinal cord lesion sites

While the anatomical properties of regenerated axons across spinal cord lesion sites have been studied extensively, little is known of how the functional properties of regenerated synapses compare to those in unlesioned animals. This comparison has been performed here in the lamprey, a model system for spinal injury research, in which functional locomotor recovery after spinal cord lesions is associated with axonal regeneration across the lesion site. Regenerated synapses below the lesion site did not differ to synapses from unlesioned axons with respect to the amplitude and duration of single excitatory postsynaptic potentials (EPSPs). They also showed the same activity-dependent depression over spike trains. However, regenerated synapses did differ to unlesioned synapses as the estimated number of synaptic vesicles was greater and there was evidence for an increased postsynaptic quantal amplitude. For axons above the lesion site, the amplitude and duration of single synaptic inputs also did not differ significantly to unlesioned animals. However, in this case there was evidence of a reduction in release probability and inputs facilitated rather that depressed over spike trains. Synaptic inputs from single regenerated axons below the lesion site thus do not increase in amplitude to compensate for the reduced number of descending axons after functional recovery. However, the postsynaptic input is maintained at the unlesioned level using different synaptic properties. Conversely, the facilitation from the same initial amplitude above the lesion site will make the synaptic input over spike trains functionally stronger. This may help to increase propriospinal activity across the lesion site to compensate for the lesion-induced reduction in supraspinal inputs.

Differential association of cortical, subcortical and spinal cord damage with multiple sclerosis disability milestones: A multiparametric MRI study

Background: In multiple sclerosis (MS), cortical, subcortical and infratentorial structural damage may have a differential contribution to clinical disability according to disease phases. Purpose: To determine the relative contributions of cortical, deep (D) grey matter (GM), cerebellar and cervical cord damage to MS disability milestones. Methods: Multi-centre 3T brain and cervical cord T2- and three-dimensional (3D) T1-weighted images were acquired from 198 MS patients (139 relapsing-remitting (RR) MS, 59 progressive (P) MS) and 67 healthy controls. Brain/cord lesion burden, cortical thickness (CTh), DGM and cerebellar volumetry and cord cross-sectional area (CSA) were quantified. Random forest analyses identified predictors of expanded disability status scale (EDSS) disability milestones (EDSS = 3.0, 4.0 and 6.0). Results: MS patients had widespread atrophy in all investigated compartments versus controls ( p-range: ⩽0.001–0.05). Informative determinants of EDSS = 3.0 were cord CSA, brain lesion volume, frontal CTh and thalamic and cerebellar atrophy (out-of-bag (OOB) accuracy = 0.84, p-range: ⩽0.001–0.05). EDSS = 4.0 was mainly predicted by cerebellar and cord atrophy, frontal and sensorimotor CTh and cord lesion number (OOB accuracy = 0.84, p-range: ⩽0.001–0.04). Cervical cord CSA ( p = 0.001) and cord lesion number ( p = 0.003) predicted EDSS = 6.0 (OOB accuracy = 0.77). Conclusion: Brain lesion burden, cortical and thalamic atrophy were the main determinants of EDSS = 3.0 and 4.0, while cord damage played a major contribution to EDSS = 6.0.