Multimodal Biomarkers Quantify Recovery in Autoimmune Autonomic Ganglionopathy.

OBJECTIVE: The objective of this study was to evaluate patients with ganglionic acetylcholine receptor antibody (gAChR-Ab) positive autoimmune autonomic ganglionopathy using a multimodal testing protocol to characterize their full clinical phenotype and explore biomarkers to quantify immunotherapy response. METHODS: We conducted a cohort study of 13 individuals (7 women, 21-69 years of age) with autonomic failure and gAChR-Ab >100 pM identified between 2005 and 2019. From 2018, all patients were longitudinally assessed with cardiovascular, pupillary, urinary, sudomotor, lacrimal and salivary testing, and Composite Autonomic Symptom Score (COMPASS-31) autonomic symptom questionnaires. The orthostatic intolerance ratio was calculated by dividing change in systolic blood pressure over time tolerated on head-up tilt. Eleven patients received immunotherapy. RESULTS: At first assessment, all 13 patients had cardiovascular and pupillary impairments, 7 of 8 had postganglionic sudomotor dysfunction, 9 of 11 had urinary retention and xeropthalmia, and 6 of 8 had xerostomia. After immunotherapy, there were significant improvements in orthostatic intolerance ratio (33.3 [17.8-61.3] to 5.2 [1.4-8.2], p = 0.007), heart rate response to deep breathing (1.5 [0.0-3.3] to 4.5 [3.0-6.3], p = 0.02), pupillary constriction to light (12.0 [5.5-18.0] to 19.0 [10.6-23.8]%, p = 0.02), saliva production (0.01 [0.01-0.05] to 0.08 [0.02-0.20] g/min, p = 0.03), and COMPASS-31 scores (52 to 17, p = 0.03). Orthostatic intolerance ratio correlated with autonomic symptoms at baseline (r = 0.841, p = 0.01) and following immunotherapy (r = 0.889, p = 0.02). Immunofluorescence analyses of skin samples from a patient 32 years after disease onset showed loss of nerve fibers supplying the dermal autonomic adnexa and epidermis, with clear improvements following immunotherapy. INTERPRETATION: Patients with autoimmune autonomic ganglionopathy demonstrated objective evidence of widespread sympathetic and parasympathetic autonomic failure, with significant improvements after immunotherapy. Quantitative autonomic biomarkers should be used to define initial deficits, guide therapeutic decisions, and document treatment response. ANN NEUROL 2021;89:753-768.

Incidence of traumatic spinal cord injury worldwide: a systematic review.

PURPOSE: Traumatic spinal cord injuries (TSCI) are among the most devastating conditions in developed and developing countries, which can be prevented. The situation of TSCI around the world is not well understood which complicates the preventive policy decision making in fight against TSCI. This study was aimed to gather the available information about incidence of TSCI around the world. METHODS: A systematic search strategy was designed and run in Medline and EMBASE, along with extensive grey literature search, personal communications, website searching, and reference checking of related papers. RESULTS: Overall, 133 resources including 101 papers, 17 trauma registries, 6 conference proceedings, 5 books, 2 theses and 2 personal communication data were retrieved. Data were found for 41 individual countries. The incidence of TSCI ranges from 3.6 to 195.4 patients per million around the world. Australia, Canada, US, and high-income European countries have various valuable reports of TSCI, while African and Asian countries lack the appropriate epidemiologic data on TSCI. CONCLUSION: Data of epidemiologic information in TSCI are available for 41 countries of the world, which are mostly European and high-income countries. Researches and efforts should be made to gather information in developing and low-income countries to plan appropriate cost-effective preventive strategies in fight against TSCI.

A rare case of spinal involvement in hereditary hemorrhagic telangiectasia.

INTRODUCTION: Here, we describe a rare case of a spinal arteriovenous fistula in a patient with known hereditary hemorrhagic telangiectasia (HHT) and spontaneous intraspinal hemorrhage. Furthermore, we provide a brief review of the literature on the formation of spinal arteriovenous malformations (AVM) in relation to this disease. CASE PRESENTATION: The case involves a 54-year-old male with known HHT. At the age of 49, the patient experienced recurrent cystitis. Urological evaluation ruled the cause to be neurological and subsequent imaging revealed a thoracic AVM. Four years later, the patient was admitted to A&E with chest pain and loss of function of the lower extremities and right arm, suspicious for ruptured aortic dissection. Trauma-CT excluded this and a final diagnosis of ruptured spinal AVM was made. Seven months post-injury, a spinal angiography was performed confirming the AVM. The remaining AVM was embolized under general anesthesia with acceptable results. DISCUSSION: Spinal involvement in HHT is exceedingly rare but remains an important differential diagnosis, especially when patients present autonomic symptoms as these could potentially progress to life-threatening complications. The literature and the presented case indicate the prudence of closing spinal AVMs in HHT in case of symptoms, including autonomic, such as bladder dysfunction.

Incidence of traumatic spinal cord injury worldwide: A systematic review, data integration, and update.

Objectives: This review was designed to update our earlier systematic review which evaluated both published and unpublished evidence on the incidence of traumatic spinal cord injury (TSCI) worldwide. Methods: We used various search methods including strategic searching, reference checking, searching for grey literature, contacting registries, authors, and organizations requesting unpublished data, browsing related websites, and hand searching key journals. The quality of included studies was evaluated by Joanna Briggs Institute Critical Appraisal Tools. Records published between April 2013 and May 2020 were added to the original systematic review. Results: Overall, 58 resources including 45 papers, 10 SCI registry reports, 1 book, and 2 theses were retrieved. We found TSCI incidence data for eight new countries, which overall shapes our knowledge of TSCI incidence for 49 countries. The incidence of TSCI ranges from 3.3 to 195.4 cases per million (cpm) based on subnational studies and from 5.1 to 150.48 cpm based on national studies. Most of the studies were low quality, lacked consistent case selection due to unclear definition of TSCI and unclear ascertainment methods. Conclusions: There is an increasing number of publications in the literature focusing on the epidemiologic data of TSCI. The absence of a standard form of reporting TSCI hinders the comparability of data across different data sources. Use of various definitions for TSCI may lead to heterogeneity in reports. Use of sensitivity analyses based on reasonable classification criteria can aid in offering a uniform set of case identification and ascertainment criteria for TSCI.

Cardiovascular complications of spinal cord injury.

BACKGROUND: The aim of this paper is to provide an overview of the autonomic innervation of the cardiovascular system and the cardiovascular sequelae of spinal cord injuries. METHOD: A literature search was carried out in the PubMed database, with the search phrases "traumatic spinal cord injury"/"traumatic spinal cord injuries" together with "autonomic dysfunction", "autonomic dysreflexia" and "cardiovascular disease". RESULTS: The most important cardiovascular complications in the acute phase are bradyarrhythmia, hypotension, enhanced vasovagal reflexes, supraventricular/ventricular ectopic beats, vasodilation and venous stasis. Important in the chronic phase are orthostatic hypotension and impaired regulation of blood pressure, blood volume and body temperature. Tetraplegia is frequently accompanied by autonomic dysreflexia, impaired transmission of cardial pain, loss of muscle mass in the left ventricle and pseudoinfarction. Patients with injuries above the sixth thoracic vertebra have a predisposition for autonomic dysreflexia. This is a condition characterised by sudden, uncontrolled sympathetic response accompanied by a rise in blood pressure. Autonomic dysreflexia usually leads to headaches and erythema on the upper chest. The condition may cause cerebral haemorrhage and is potentially life threatening. Patients with spinal cord injuries have an increased risk of atherosclerotic disease due to overweight, lipid disorders, metabolic syndrome and diabetes. They are predisposed to thrombotic emboli due to venous stasis and hypercoagulopathy, particularly immediately after the injury. INTERPRETATION: Knowledge of cardiovascular sequelae after spinal cord injuries and assessment of these is important for correct diagnostics, planning of preventive measures and optimal treatment.

Spasticity following spinal cord injury.

BACKGROUND: Up to 70% of patients with spinal cord injuries develop spasticity. The main aim of the paper is to provide an overview of spasticity management, primarily in patients with spinal cord injuries. METHOD: The article is based on literature searches in PubMed using the keyphrases «spasticity¼ and «spasticity AND spinal cord injury¼, and own clinical experience and research. RESULTS: Spasticity may be general, regional or localised. Factors such as an over-filled bladder, obstipation, acute infections, syringomyelia or bone fractures may substantially influence the degree of spasticity and must be determined. An assessment of the clinical and functional consequences for the patient is decisive before management. Active exercise, physiotherapy and peroral drugs are the simplest and cheapest options. Baclofen is the only centrally acting spasmolytic registered in Norway and is the first choice for peroral treatment. Benzodiazepines can also be used. The effect of the tablets is generally limited and there are often pronounced side effects. Local spasticity can be treated with botulinum toxin injections. The effect is time-limited and the treatment must be repeated. International guidelines recommend a combination of botulinum toxin injections and physiotherapy. In cases of regional spasticity, particularly in the lower limbs, intrathecal baclofen administered via a programmable pump may provide a continuous spasm-reducing effect. Orthopaedic surgery or neurosurgery may be an option for selected patients with intractable spasticity. INTERPRETATION: Spasticity following a spinal cord injury must be assessed regularly. The treatment strategy depends on the degree of functional failure caused by the spasticity and its location.

Chronic pain following spinal cord injury.

BACKGROUND: Chronic pain following spinal cord injury is common, and may result in a substantially reduced quality of life. The aim of the paper is to provide an overview of pain conditions resulting from spinal cord injuries and an update on therapy options. METHOD: The article is based on literature searches in PubMed review articles for the period 2006-2011, using the search phrases «pain and spinal cord injury/injuries¼, «chronic pain and spinal cord injury/injuries¼ and «neuropathic pain and spinal cord injury/injuries¼. Some key articles on neuropathic pain are also included, irrespective of the year of publication. RESULTS: Patients with spinal cord injury may develop nociceptive and/or neuropathic pain.The cause, nature and localisation of the pain must be established before therapy is initiated. Neuropathic pain should primarily be treated with amitriptyline, gabapentin or pregabalin. Duloxetine, lamotrigine and tramadol may also be effective. Local treatment with high-concentration capsaicin and lidocaine may relieve localised neuropathic pain. Selected patients with intractable chronic neuropathic pain can be treated with intrathecal medication using an implanted pain pump or by microsurgical DREZotomy (Dorsal Root Entry Zone). Physiotherapy, non-steroidal anti-inflammatory drugs and opioids are most widely used for treating nociceptive pain. Physical exercise and acupuncture may provide relief from shoulder pain. INTERPRETATION: There may be several causes of chronic pain following spinal cord injury. Different measures have been tested for the management of chronic pain after spinal cord injury, but most studies have been performed on a limited number of patients. Further studies are needed to find more effective means of relieving pain following spinal cord injuries.

Traumatic spinal cord injuries--incidence, mechanisms and course.

BACKGROUND: The primary purpose of this article is to provide an overview of demography, neurological level of injury, extent of lesion, incidence, prevalence, injury mechanisms as well as lethality and causes of death associated with traumatic spinal cord injuries. MATERIAL AND METHOD: A literature search was carried out in PubMed, with the search words "traumatic spinal cord injury"/"traumatic spinal cord injuries" together with "epidemiology", and "spinal cord injury"/"spinal cord injuries" together with "epidemiology". RESULTS: The reported annual incidence of traumatic spinal cord injuries varies from 2.3 per million in a study from Canada to 83 per million in Alaska. The prevalence is given as ranging from 236 per million in India to 1800 per million in the USA. The average age at the time of injury varies from 26.8 years in Turkey to 55.5 years in the USA. The ratio of men to women varies from 0.9 in Taiwan to 12.0 in Nigeria. The most frequent cause of injury is traffic accidents, followed by falls, violence and sports/leisure activity incidents. Patients with traumatic spinal cord injuries have a higher lethality than the normal population. The most frequent causes of death today are airway problems, heart disease and suicide. INTERPRETATION: There are large geographical differences in reported incidence, prevalence and lethality. This is attributable to differences in definition, inclusion, classification and patient identification procedures in the various studies, together with geographical and cultural differences and differences in prehospital and hospital treatment.

[Pressure ulcers after spinal cord injury]. / Trykksår etter ryggmargsskade.

BACKGROUND: Pressure ulcers are a serious and frequently occurring complication in patients with a traumatic spinal cord injury. The purpose of the article is to consider the causes of pressure ulcers and how to prevent them. METHOD: The article is based on a non-systematic search in the PubMed database and own clinical experience. RESULTS: 30-40 % of patients with spinal cord injuries develop pressure ulcers during the acute and rehabilitation phases, most frequently over bony prominences such as the sacrum, tuber ischii, heel, malleolus and trochanter. Risk factors are reduced activity/immobility, lack of sensibility, moisture due to urinary or faecal incontinence, muscular atrophy, prolonged time since injury, depression, smoking and poor nutrition. The most important preventive measures are pressure relief, regular change of position and frequent observation of the skin over bony prominences. INTERPRETATION: In most cases, patients with traumatic spinal cord injuries can be prevented from developing pressure ulcers. Prevention saves patients from long-term hospitalisation and the healthcare system from high costs.

Autonomic dysreflexia and concurrent Horner's Syndrome: a rare presentation in a patient with spinal cord injury.

INTRODUCTION: Autonomic dysreflexia is an uninhibited sympathetic response evoked by a strong sensory input below the level of the injury in patients with spinal cord injury. As presented in this case, autonomic dysreflexia can be associated with unusual symptoms such as Horner's syndrome. CASE PRESENTATION: An 18-year-old man with a traumatic spinal cord injury (C7 AIS A) experienced symptoms of unilateral Horner's syndrome: miosis, ptosis and anhidrosis which occurred simultaneously with symptoms of autonomic dysreflexia: severe headache accompanied by increasing right-sided diaphoresis, flushing, blurred vision, and increased blood pressure. These symptoms were triggered by bladder distention and were resolved after catheterisation. DISCUSSION: The patient experienced a transient Horner's syndrome due to autonomic dysreflexia. Both Horner's syndrome and symptoms of autonomic dysreflexia resolved when eliminating the eliciting stimulus, indicating that Horner's syndrome occurred due to a transient pressure on the sympathetic fibres supplying the superior cervical ganglion. Autonomic dysreflexia may have caused increased pressure disrupting the sympathetic input, thus inducing unilateral miosis, ptosis, and facial anhidrosis.

Autonomic cardiovascular dysfunction during simple arithmetic test in a patient with cervical spinal cord injury-a case report.

INTRODUCTION: Spinal cord injury (SCI) disrupts autonomic control of the cardiovascular system, which may lead to autonomic dysfunction. Growing amounts of evidence support the possibility that systemic and cerebral hemodynamic dysfunctions may contribute to cognitive deficits in patients with SCI. CASE PRESENTATION: We present a case of autonomic cardiovascular dysfunction in a 55-year old female patient following non-traumatic cervical SCI. This case illustrates how a simple arithmetic test may elicit fluctuations in blood pressure causing cognitive disturbances. DISCUSSION: Clinical awareness of autonomic dysfunction and cognitive deficits is relevant in neurorehabilitation of patients with SCI. Assessment of autonomic function should be evaluated according to recommendation from International Standards to document remaining Autonomic Function after Spinal Cord Injury (ISAFSCI) [1].

Postprandial Hypotension and Spinal Cord Injury.

Postprandial hypotension (PPH) is defined as a fall of ≥20 mmHg in systolic blood pressure (SBP) or a SBP of <90 mmHg after having been >100 mmHg before the meal within two hours after a meal. The prevalence of PPH among persons with spinal cord injury (SCI) is unknown. Ambulatory blood pressure measurement was performed in 158 persons with SCI, 109 men, median age was 59.1 years (min.:13.2; max.: 86.2). In total, 78 persons (49.4%) had PPH after 114 out of 449 meals (25.4%). The median change in SBP during PPH was -28 mmHg (min.: -87; max.: -15 mmHg) and 96% of the PPH episodes were asymptomatic. The occurrence of PPH was correlated to older age (p = 0.001), level of injury (p = 0.023), and complete SCI (p = 0.000), but not, gender or time since injury. Further studies are needed to elucidate if PPH contributes to the increased cardiovascular mortality in the SCI population.

Mortality after traumatic spinal cord injury: 50 years of follow-up.

OBJECTIVE: To study mortality and causes of death in an unselected geographically defined cohort of patients with traumatic spinal cord injury (TSCI), 1952-2001. METHODS: Patients were identified from hospital records. The date of death was obtained from the National Population Register, and causes of death recorded by linkage to the Norwegian Cause of Death Registry. Patient mortality was compared with mortality in the Norwegian population using standardised mortality ratios (SMR) adjusted for age and gender. RESULTS: 401 patients (70 women and 331 men) were identified. By 31 August 2008, 173 were dead. Median survival time in deceased patients was 7.4 years; 6.9 years for patients with cervical injuries and 8.2 years for patients with thoracolumbosacral injuries (TLS). TSCI patients had an increased mortality (SMR 1.85) compared with the Norwegian population. SMR did not change during the observation period. SMR was significantly higher for women than for men (2.88 vs 1.72), and higher in patients with complete TSCI compared with patients with incomplete TSCI (4.23 vs 1.25). SMR was 6.70 for patients with complete cervical injuries and 3.07 for patients with complete TLS injuries. Cause specific SMR were 1.96 for respiratory disease, and for suicide including accidental poisoning 3.70 for men and 37.59 for women. CONCLUSIONS: Patients with a TSCI, and especially women, have an increased mortality despite modern treatment and care. Special attention should be paid to respiratory dysfunction and pulmonary infections, and to prevent suicide and accidental poisoning.

Fatal autonomic failure due to premanifesting Parkinson's disease only diagnosed at autopsy.

A 46-year-old male had 11-year history of cryptic autonomic dysfunction. He developed a fatal autonomic failure with diffuse hypoxic brain injury. Histology examination of medulla oblongata and the celiac ganglion revealed many α-synuclein immunoreactive Lewy bodies confirming the diagnosis of premanifesting Parkinson's disease (PD). PNS involvement in PD is underappreciated.

Thermodysregulation in persons with spinal cord injury: case series on use of the autonomic standards.

INTRODUCTION: The ability to maintain core body temperature (Tcore) within a narrow range (37 ± 0.6 °C), despite exposure to a wide range of ambient temperatures, is essential in order to provide an optimal environment for vital organs, the central nervous system (CNS), and cellular processes to function. High-level (above T6) spinal cord injury (SCI) interrupts the autonomic nervous system's ability to carry out hypothalamic regulation of thermoregulatory mechanisms for both heat dissipation and conservation. This interruption leaves persons with high-level SCI vulnerable to hyper and hypothermia even during exposure to relatively mild ambient temperatures. The goal of the Autonomic Standards is to enable the clinician to quickly identify those individuals with SCI who may be most at risk for thermoregulatory dysfunction. CASE PRESENTATION: Case 1: Heat Exhaustion, Case 2: Heat Stroke in absence of CNS symptoms, Case 3: Heat Exhaustion. DISCUSSION: The three cases demonstrate the signs and symptoms that may accompany hyperthermia in persons with SCI. The onset may be quite rapid and the condition persistent, despite ambient temperatures being much less intense than expected to be necessary to induce similar conditions in able-bodied (AB) persons. The responses of the persons in the case studies to the temperature regulation and autonomic control of sweating sections of the Autonomic Standards would identify them as being vulnerable and warrant providing appropriate exposure guidelines and precautions to them and their caregivers.

Cannabis use in persons with traumatic spinal cord injury in Denmark.

OBJECTIVE: To evaluate recreational and medical cannabis use in individuals with traumatic spinal cord injury, including reasons and predictors for use, perceived benefits and negative consequences. DESIGN: Cross-sectional survey in Denmark. METHODS: A 35-item questionnaire was sent to 1,101 patients with spinal cord injury who had been in contact with a rehabilitation centre between 1990 and 2012. RESULTS: A total of 537 participants completed the questionnaire. Of these, 36% had tried cannabis at least once and 9% were current users. Of current users, 79% had started to use cannabis before their spinal cord injury. The main reason for use was pleasure, but 65% used cannabis partly for spinal cord injury-related consequences and 59% reported at least good effect on pain and spasticity. Negative consequences of use were primarily inertia and feeling quiet/subdued. Lower age, living in rural areas/larger cities, tobacco-smoking, high alcohol intake and higher muscle stiffness were significantly associated with cannabis use. Those who had never tried cannabis reported that they would mainly use cannabis to alleviate pain and spasticity if it were legalized. CONCLUSION: Cannabis use is more frequent among individuals with spinal cord injury in Denmark than among the general population. High muscle stiffness and various demographic characteristics (lower age, living in rural areas/larger cities, tobacco-smoking and high alcohol intake) were associated with cannabis use. Most participants had started using cannabis before their spinal cord injury. There was considerable overlap between recreational and disability-related use.

Feasibility and Data Quality of the National Spinal Cord Injury Registry of Iran (NSCIR-IR): A Pilot Study.

BACKGROUND: Spinal cord injury (SCI) is one of the most disabling consequences of trauma with unparalleled economic, social, and personal burden. Any attempt aimed at improving quality of care should be based on comprehensive and reliable data. This pilot investigation studied the feasibility of implementing the National Spinal Cord and Column Injury Registry of Iran (NSCIR-IR) and scrutinized the quality of the registered data. METHODS: From October 2015 to May 2016, over an 8-month period, 65 eligible trauma patients who were admitted to hospitals in three academic centers in mainland Iran were included in this pilot study. Certified registered nurses and neurosurgeons were in charge of data collection, quality verification, and registration. RESULTS: Sixty-five patients with vertebral column fracture dislocations were registered in the study, of whom 14 (21.5%) patients had evidence of SCI. Mechanisms of injury included mechanical falls in 30 patients (46.2%) and motor vehicle accidents in 29 (44.6%). The case identification rate i.e. clinical and radiographic confirmation of spine and SCI, ranged from 10.0% to 88.9% in different registry centers. The completion rate of all data items was 100%, except for five data elements in patients who could not provide clinical information because of their medical status. Consistency i.e. identification of the same elements by all the registrars, was 100% and accuracy of identification of the same pathology ranged from 66.6% to 100%. CONCLUSIONS: Our pilot study showed both the feasibility and acceptable data quality of the NSCIR-IR. However, effective and successful implementation of NSCIR-IR data use requires some modifications such as presence of a dedicated registrar in each center, verification of data by a neurosurgeon, and continuous assessment of patients' neurological status and complications.