Spinal Cord Involvement Research Articles

Developmental delay and late onset HBSL pathology in hypomorphic Dars1M256L mice

The leukodystrophy Hypomyelination with Brainstem and Spinal cord involvement and Leg spasticity (HBSL) is caused by recessive mutations of the DARS1 gene, which encodes the cytoplasmic aspartyl-tRNA synthetase. HBSL is a spectrum disorder with disease onset usually during early childhood and no available treatment options. Patients display regression of previously acquired motor milestones, spasticity, ataxia, seizures, nystagmus, and intellectual disabilities. Gene-function studies in mice revealed that homozygous Dars1 deletion is embryonically lethal, suggesting that successful modelling of HBSL requires the generation of disease-causing genocopies in mice. In this study, we introduced the pathogenic DARS1M256L mutation located on exon nine of the murine Dars1 locus. Despite causing severe illness in humans, homozygous Dars1M256L mice were only mildly affected. To exacerbate HBSL symptoms, we bred Dars1M256L mice with Dars1-null ‘enhancer’ mice. The Dars1M256L/− offspring displayed increased embryonic lethality, severe developmental delay, reduced body weight and size, hydrocephalus, anophthalmia, and vacuolization of the white matter. Remarkably, the Dars1M256L/− genotype affected energy metabolism and peripheral organs more profoundly than the nervous system and resulted in reduced body fat, increased respiratory exchange ratio, reduced liver steatosis, and reduced hypocellularity of the bone marrow. In summary, homozygous Dars1M256L and compound heterozygous Dars1M256L/− mutation genotypes recapitulate some aspects of HBSL and primarily manifest in developmental delay as well as metabolic and peripheral changes. These aspects of the disease might have been overlooked in HBSL patients with severe neurological deficits but could be included in the differential diagnosis of HBSL in the future.

Spinal cord involvement in tuberculous meningitis: a case report and brief review of literature

Introduction: Tuberculosis (TB) continues to pose a significant public health problem worldwide. Tuberculous meningitis (TBM) is the most devastating form of extrapulmonary TB however other forms of central nervous system (CNS) disease include tuberculoma and spinal arachnoiditis. TBM carries high mortality even for a patient who is already receiving treatment. The difficulty in diagnosis often leads to a delay in treatment and subsequent mortality. The emergence of Xpert ultra has improved the rapid detection of MTB and rifampicin resistance in CSF and is the preferred diagnostic tool in TBM. Case: In this case report we present a 33years patient of concern who presented with progressive lower limb weakness associated with pain and paresthesia for 4 months, admitted via the Orthopedic unit with a diagnosis of spinal mass (meningioma, neurofibroma, or nerve sheath tumor) for which biopsy was done and revealed a chronic inflammatory process, necrotic bone lesions with no granulomas and no malignancy, he was later diagnosed with tuberculous meningitis and promptly started anti-tuberculous therapy with a dramatic recovery and improvement in neurological function. Conclusion: Tuberculous meningitis conditions have high morbidity and mortality yet diagnosis and start of treatment continue to experience an important delay. Clinicians should keep in mind the limitations of clinical presentation due to pleiotropy and current diagnostics and should employ a combination of diagnostic modalities in addition to a high index of suspicion to prevent morbidity in patients with TBM.

Wearable sensors detect impaired gait and coordination in LBSL during remote assessments

BackgroundLeukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a rare leukodystrophy with motor impairment due to biallelic mutations in DARS2, which encodes mitochondrial aspartyl tRNA synthetase. Progressive ataxia is the primary feature.ObjectiveThe study objective is to determine the feasibility of remotely collecting quantitative gait and balance measures in LBSL.MethodsThe study design uses wearable accelerometers and the scale for the assessment and rating of ataxia (SARA) scale to assess gait and postural sway in LBSL and control participants' homes through video conferencing.ResultsLateral step variability (LSV), which indicates stride variability, and elevation of the step at mid‐swing are increased for LBSL patients during brief walking tests. During stance with the eyes closed, LBSL participants show rapid accelerations and decelerations of body movement covering a large sway area and path. Both the LSV and sway area during stance with the feet together and eyes closed correlate strongly with the SARA.ConclusionsWearable accelerometers are valid and sensitive for detecting ataxia in LBSL patients during remote assessments. The finding of large increases in the sway area during stance with the eyes closed is intriguing since dorsal column dysfunction is universally seen in LBSL. This approach can be applied to related rare diseases that feature ataxia.

Diagnosis, treatment, and outcome of primary CNS lymphoma—a single-center experience

Primary CNS lymphoma (PCNSL) is a highly aggressive non-Hodgkin lymphoma (NHL) that occurs in the CNS (e.g. brain, meninges, spinal cord, cerebrospinal fluid, or intraocular involvement) in the absence of systemic NHL. Tumor resection does not improve survival, and neurosurgical intervention is generally limited to stereotactic biopsy to provide a histopathological diagnosis. The objective of this single-center study was to evaluate the management and outcome of PCNSL patients diagnosed by biopsy, using overall survival and progression-free survival as endpoints. At our department of neurosurgery, 140 patients were diagnosed with PCNSL by biopsy between January 1, 2009, and December 31, 2018. Of these, 37 patients were included in the study and were divided into three groups according to their postoperative therapy. Median OS was 35.7months for the intensive treatment group, 29.5months for the moderate treatment group, and 8.6months for the palliative treatment group. The intensive and moderate treatment groups had similar progression-free survival, while the palliative treatment group had poor overall and progression-free survival. Six patients were long-term survivors (> 80months). Age under 65years was the main significant parameter affecting overall survival. In this cohort, patients with PCNSL had an overall fair prognosis if they (1) were under 65years old, (2) had a performance score < 2 at the time of diagnosis, and (3) received either intensive or moderate chemotherapeutic treatment. Biopsy is still the primary diagnostic tool; other methods have been investigated but are not yet recommended.

Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation (LBSL) Based on Typical MRI and MRS Findings: A Case Report

Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation (LBSL) Based on Typical MRI and MRS Findings: A Case Report

Influence of prehospital management on the outcome of spinal cord decompression sickness in scuba divers

BackgroundDecompression sickness (DCS) with spinal cord involvement has an unfortunately high rate of long-term sequelae. The objective of this study was to determine the association of prehospital variables on the...

Paraparesis as a Rare Complication of Dengue Fever Causing Spontaneous Spinal Subarachnoid Haemorrhage

A smaller number of confirmed dengue cases worldwide present with neurological symptoms such as headache, seizure, neck stiffness, drowsiness, altered sensorium, behavioural disorders, delirium, cranial nerves palsies, and rarely, spinal cord involvement. This report is about a 54-year-old female patient with dengue, who presented with acute spinal cord compression due to spontaneous spinal Subarachnoid Haemorrhage (SAH). She complained of sudden onset of febrile illness associated with headache, myalgia, retro-orbital pain, and low backache for three days, followed by sudden onset paraplegia three days after the onset of the illness. A haemogram was obtained, which showed a platelet count of 60,000/µL. She had antibodies against dengue NS1 and dengue Immunoglobulin M (IgM), but not against dengue IgG. A Magnetic Resonance Imaging (MRI) spine contrast imaging revealed a spinal SAH from the level of T12 to L1, as well as significant cord compression. An MRI of the brain revealed a SAH in the bilateral parieto-occipital region. She underwent an emergency laminectomy and complete haematoma evacuation. Postsurgical period was uneventful with complete recovery of sensation and weakness. In patients from endemic areas of dengue infection who present with fever and spinal cord involvement a high degree of suspicion of this disease should arise and it should always be investigated further for dengue-related neurological complications.

Isolated Intramedullary Cervical Spinal Cord Cysticercosis- A Case Report

Neurocysticercosis is the most prevalent parasitic infection in developing countries, caused by the encysted larvae of taenia solium. It predominantly affects the brain alone or both the brain and the spinal cord. In spinal cysticercosis, the thoracic cord is most commonly involved. Isolated involvement of the cervical spinal cord is very rare. Authors report the case of a 19-year-old male patient with intramedullary cysticercosis in the cervical cord. The lesion was diagnosed with magnetic resonance imaging and serology. Albendazole and steroids were used to treat the patient medically

Movement Disorder in Demyelinating Disease: Tracing the Charcot's Foot Print.

Movement disorders may be one of the neurological manifestations of demyelinating disorders. They can manifest in Parkinsonism or a wide spectrum of hyperkinetic movement disorders including tremor, paroxysmal dyskinesia, dystonia, chorea, and ballism. Some of these disorders occur during an acute episode of demyelination, whereas others can develop later or even may precede the onset of the demyelinating disorders. The pathophysiology of movement disorders in demyelination is complex and the current evidence indicates a wide involvement of different brain networks and spinal cord. Treatment is mainly symptomatic and oral pharmacological agents are the mainstay of the management. Botulinum toxin and neurosurgical interventions may be required in selected patients.

Acute Spinal Cord Dysfunction Following COVID-19 Infection: A Case Report

Here, we describe a 44-year-old female that developed abrupt symptomatology, including lower-limb paralysis with sensory involvement at the T12 level, two weeks after the resolution of COVID-19 bilateral pneumonia. Based on the neurological symptoms and the neurophysiological investigations, a clinical diagnosis of thoracic spinal cord dysfunction was made. However, all the complementary tests performed showed normal results. In particular, repeated MRIs showed no alterations; the cerebrospinal fluid analysis showed normal results: the CT scan of the brain was normal and the CT scan of the abdominal and thoracic aorta showed a normal size and course. Cases of spinal cord involvement have rarely been described, in which the MRIs never revealed cord signaling changes. We hypothesize that a small vessel spinal cord stroke might explain the pathogenesis and the absence of changes detectable on an MRI along with the patient's modest recovery during the long follow up. However, it cannot be excluded that the severe clinical course of SARS-CoV-2 infection, may suggest other different etiologies that could be related to prolonged hospitalization.

Detection of spinal long fiber tract degeneration in HSP: Improved diffusion tensor imaging

Spinal diffusion tensor imaging (sDTI) is still a challenging technique for selectively evaluating anatomical areas like the pyramidal tracts (PT), dorsal columns (DC), and anterior horns (AH) in clinical routine and for reliably quantifying white matter anisotropy and diffusivity. In neurodegenerative diseases, the value of sDTI is promising but not yet well understood.The objective of this prospective, single-center study was to evaluate the long fiber tract degeneration within the spinal cord in normal aging (n = 125) and to prove its applicability in pathologic conditions as in patients with molecular genetically confirmed hereditary spastic paraplegias (HSP; n = 40), a prototypical disease of the first motor neuron and in some genetic variants with affection of the dorsal columns. An optimized monopolar Stejskal-Tanner sequence for high-resolution, axial sDTI of the cervical spinal cord at 3.0 T with advanced standardized evaluation methods was developed for a robust DTI value estimation of PT, DC, and AH in both groups.After sDTI measurement at C2, an automatic motion correction and an advanced semi-automatic ROI-based, standardized evaluation of white matter anisotropy and diffusivity was performed to obtain regional diffusivity measures for PT, DC, and AH. Reliable and stable sDTI values were acquired in a healthy population without significant decline between age 20 and 65. Reference values for PT, DC, and AH for fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) were established.In HSP patients, the decline of the long spinal fiber tracts could be demonstrated by diffusivity abnormalities in the pyramidal tracts with significantly reduced PTFA (p < 0.001), elevated PTRD (p = 0.002) and reduced PTMD (p = 0.003) compared to healthy controls. Furthermore, FA was significantly reduced in DCFA (p < 0.001) with no differences in AH. In a genetically homogeneous subgroup of SPG4 patients (n = 12) with affection of the dorsal columns, DCRD significantly correlated with the overall disease severity as measured by the Spastic Paraplegia Rating Scale (SPRS) (r = − 0.713, p = 0.009).With the most extensive sDTI study in vivo to date, we showed that axial sDTI combined with motion correction and advanced data post-processing strategies enables robust measurements and is ready to use, allowing recognition and quantification of disease- and age-related changes of the PT, DC, and AH. These results may also encourage the usage of sDTI in other neurodegenerative diseases with spinal cord involvement to explore its capability as selective biomarkers.

Sports-Related Neurologic Injuries: More Than Just Concussion

Describe important patterns of neurologic injury in sports related trauma. Sports related neurologic trauma represents a unique, complex pattern of injury with potential significant impactful morbidity. An estimated 8.6 million sports injuries occur annually, 300,000 of which result in traumatic brain injury (TBI). The incidence of other nervous system injury is underreported. Retrospective analysis of consecutive patients who presented to an emergency department between January 1, 2015 and January 1, 2020 with a sports related injury. Characterization of neurologic vs non-neurological bodily injury, sports activity, and demographic data were collected. Out of 15,525 patients with sports injuries, 390 sustained neurologic involvement of which 50% were between 1-18 years of age. Although TBI represented the majority (85%) of neurologic injury, 5.6% sustained spinal cord involvement and 5.1% had peripheral nerve injury. Spinal cord and peripheral nerve involvement were associated with prolonged hospitalization when compared to those with mild-moderate concussion X2 (1, N = 199) = 5.73, p = 0.0167. Spinal cord and peripheral nerve injury represent the minority of sports related neurologic involvement, however, may lead to significant prolonged hospitalization, morbidity and mortality.

Spinal Cord Involvement in Adult Mitochondrial Diseases: A Cohort Study.

The central nervous system is metabolically very demanding and consequently vulnerable to defects of the mitochondrial respiratory chain. While the clinical manifestations and the corresponding radiological findings of the brain involvement in mitochondrial diseases (e.g., stroke-like episodes, signal changes of the basal ganglia, cerebral and cerebellar atrophy) are well known, at present there are few data on the spinal-cord abnormalities in these pathologies, in particular in adult subjects. In this study, we present a cross-sectional cohort study on the prevalence and characterization of spinal-cord involvement in adult patients with genetically defined mitochondrial diseases.

Paravertebral hydatid cyst: A rare case report

Hydatidosis is a common disease in cattle-raising areas and mostly involves liver (65-75%), lungs (25-30%) and less commonly bones, spine, spleen, pericardium, myocardium and muscles. Muscular hydatidosis especially in paravertebral muscles is very rare. This article presents a case of paravertebral hydatidosis without spinal cord involvement which she was treated by surgery and medication. Therefore, hydatid cyst should be considered as one of the differential diagnoses of all cystic lesions especially in endemic areas. This provides an opportunity to being technically prepared to choose the right approach of intervention and treatment.

Peri-Caecal internal hernia: A case report and review of the literature

Hydatidosis is a common disease in cattle-raising areas and mostly involves liver (65-75%), lungs (25-30%) and less commonly bones, spine, spleen, pericardium, myocardium and muscles. Muscular hydatidosis especially in paravertebral muscles is very rare. This article presents a case of paravertebral hydatidosis without spinal cord involvement which she was treated by surgery and medication. Therefore, hydatid cyst should be considered as one of the differential diagnoses of all cystic lesions especially in endemic areas. This provides an opportunity to being technically prepared to choose the right approach of intervention and treatment.

Vertebral Body Infarction after Transarterial Preoperative Embolization of a Vertebral Hemangioma.

Vertebral hemangioma resection can be a real challenge for spine surgeons, given the high potential of massive intraoperative bleeding. For this reason, preoperative transarterial embolization of this tumor is supported by the available literature. Here, we discuss our difficulties in interpreting an unusual clinical and radiologic picture related to the endovascular procedure. A 45-year-old man was referred to our department due to chronic back pain and progressive lower extremity weakness. Radiologic assessment was obtained by means of spinal computed tomography (CT) and magnetic resonance imaging (MRI), which showed an aggressive vertebral hemangioma in T7, compressing the spinal cord. The patient underwent a combined therapeutic approach consisting of preoperative transarterial embolization followed by tumor resection, spinal cord decompression, and posterior thoracic arthrodesis. The patient was dismissed with neither strength nor sensory deficits. Two weeks later, he returned to our department with fever. A new MRI demonstrated multiple areas of altered signal in almost all vertebral bodies from T6 down to the sacrum. After a deep diagnostic process, including new MRI and infectious disease evaluations, the definitive diagnosis of multiple vertebral bone infarction was suggested. Vertebral infarctions are an extremely rare complication of spinal endovascular procedures. To our knowledge, this is the first case of multiple postembolization vertebral infarctions, without spinal cord involvement. This peculiarity was explained by the presence of direct anastomoses between a posterior intercostal artery and the underlying vertebral bodies.

The no evidence of disease activity (NEDA) concept in MS: impact of spinal cord MRI.

Measures to define treatment response, such as no evidence of disease activity (NEDA), are routinely used in multiple sclerosis (MS) clinical practice. Although spinal cord involvement is a frequent feature of MS, its magnetic resonance imaging (MRI) monitoring is not routinely performed. To assess the impact of spinal cord MRI in the definition of NEDA in a cohort of people with MS (pwMS) with available spinal cord imaging performed as for routine monitoring. We included 115 pwMS undergoing treatment with first-line disease-modifying therapies (DMTs) and retrospectively analyzed the presence of NEDA in the whole cohort, either considering or not spinal cord imaging. When considering only clinical and brain MRI measures, 97 out of 115 pwMS (84.3%) satisfied the criteria for NEDA. In the same cohort, the number of pwMS with NEDA significantly decreased to 88 (76.5%) (p < 0.01) when considering also spinal cord imaging. These findings suggest that, in routine clinical practice, spinal cord MRI monitoring in pwMS under first-line DMTs leads to a slight but significant change in the proportion of subjects classified as clinically and radiologically stable according to the NEDA definition.

Isolated CNS Hemophagocytic Lymphohistiocytosis in Children:What We Know, What We Don't Know ?

The presence of central nervous system involvement has a profound impact on the prognosis, treatment, and clinical outcome of the primary hemophagocytic lymphohistiocytosis (pHLH). However, isolated CNS-HLH is a challenging disease with a high mortality and morbidity , possibly resulting from a spsecific neuroinflammation that leads to isolated disease only without systemic activation under some additional genetic modifiers. In this study, we retrospectively reviewed our isolated CNS-HLH cases and there were 73 patients (36 male, 37 female) with a median age of 20 months (range, 1- 226 months) diagnosed as primary hemophagocytic lymphohistiocytosis at Hacettepe University Faculty of Medicine, between January 2005 and June 2021. Among these, 39 (53%) patients had central nervous system involvement either on admission or during the recurrence. On admission, the number of patients who had both CNS and sytemic involvement was 19 (49%), moreover 2 had CNS infiltration both initially and during the course of relapse. 8 patient did show CNS involvement only during the relapse. Ten (25%) patients (5 male, 5 female) with isolated CNS involvement are the main subject of this study and none of them had infectious trigger. What we know is they were presented with mostly unexplained neurological findings and /or cranial nerve paralysis. In this group median age at presentation was 101 months ( range 6 - 180 months). They all had primary HLH associated patogenic mutation and in some of them diagnosed was also confirmed by brain biopsy. Neither family history and /or consanguinity nor HLH criteria are fullfilling in this devastating disorder. Cranial MRI gives many clues during admission in experienced hands. Two of our published cases were initially diagnosed as lymphomatoid granulomatosis and acute disseminated encephalomyelitis ; they were diagnosed as hemophagocytic lymphohistiocytosis after developing systemic symptoms 3 and 12 months later. Interestingly 6 of 10 patients in this group never developed systemic symptomps, 7 patients underwent allogeneic bone marrow transplantation. Spinal cord involvement was determined in 8 patients(20%), including 4 at diagnosis and 4 during follow up ; including one previously published case, 4 out of 8 had isolated cases did show spinal involvement as well. Even though few number of cases with isolated CNS-HLH has been reported in the recent years, we believe that the number of such cases is not limited to those who have been reported because it is rather difficult to diagnose patients with isolated CNS symptoms, which leads to misdiagnosis and/or mistreatment. What we don't know is how to specifically treat patients with CNS directed therapy, and exactly which mutations are associated with isolated CNS-HLH or whether there is a known tendency in this group and perhaps unknown mutations ? Does it have a facilitating effect ? DisclosuresNo relevant conflicts of interest to declare.

Predictors of relapse in MOG antibody associated disease: a cohort study

ObjectiveTo identify factors predictive of relapse risk and disability in myelin oligodendrocyte glycoprotein associated disease (MOGAD).SettingPatients were seen by the neuromyelitis optica spectrum disorders (NMOSD) service in Liverpool, UK, a...

Myelin Oligodendrocyte Glycoprotein-Immunoglobulin G in the CSF: Clinical Implication of Testing and Association With Disability.

Background and ObjectiveTo investigate the clinical relevance of CSF myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG) testing in a large multicenter cohort.MethodsIn this multicenter cohort study, paired serum-CSF samples from 474 patients with suspected inflammatory demyelinating disease (IDD) from 11 referral hospitals were included. After serum screening, patients were grouped into seropositive myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD, 31), aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG + NMOSD, 60), other IDDs (217), multiple sclerosis (MS, 45), and non-IDDs (121). We then screened CSF for MOG-IgG and compared the clinical and serologic characteristics of patients uniquely positive for MOG-IgG in the CSF to seropositive patients with MOGAD.ResultsNineteen patients with seropositive MOGAD (61.3%), 9 with other IDDs (CSF MOG + IDD, 4.1%), 4 with MS (8.9%), but none with AQP4-IgG + NMOSD nor with non-IDDs tested positive in the CSF for MOG-IgG. The clinical, pathologic, and prognostic features of patients uniquely positive for CSF MOG-IgG, with a non-MS phenotype, were comparable with those of seropositive MOGAD. Intrathecal MOG-IgG synthesis, observed from the onset of disease, was shown in 12 patients: 4 of 28 who were seropositive and 8 who were uniquely CSF positive, all of whom had involvement of either brain or spinal cord. Both CSF MOG-IgG titer and corrected CSF/serum MOG-IgG index, but not serum MOG-IgG titer, were associated with disability, CSF pleocytosis, and level of CSF proteins.DiscussionCSF MOG-IgG is found in IDD other than MS and also in MS. In IDD other than MS, the CSF MOG-IgG positivity can support the diagnosis of MOGAD. The synthesis of MOG-IgG in the CNS of patients with MOGAD can be detected from the onset of the disease and is associated with the severity of the disease.Classification of EvidenceThis study provides Class II evidence that the presence of CSF MOG-IgG can improve the diagnosis of MOGAD in the absence of an MS phenotype, and intrathecal synthesis of MOG-IgG was associated with increased disability.