Salsalate Improves Postprandial Glycemic and Some Lipid Responses in Persons With Tetraplegia: A Randomized Clinical Pilot Trial With Crossover Design.

Objectives: To investigate the effects of salsalate on fasting and postprandial (PP) glycemic, lipidemic, and inflammatory responses in persons with tetraplegia. Methods: This study was a randomized, double-blind, cross-over design. It was conducted at a university laboratory. Ten males aged 25 to 50 years with SCI at C5-8 levels for ≥1 year underwent 1 month of placebo and salsalate (4 g/day) treatment. Blood samples were drawn before and 4 hours after breakfast and lunch fast-food meal consumption. Results: Descriptive statistics indicate that fasting and PP glucose values were reduced with salsalate (pre-post mean difference, 4 ± 5 mg/dL and 8 ± 8 mg/dL, respectively) but largely unchanged with placebo (0 ± 6 mg/dL and -0 ± 7 mg/dL, respectively). Insulin responses were generally reciprocal to glucose, however less pronounced. Fasting free fatty acids were significantly reduced with salsalate (191 ± 216 mg/dL, p = .021) but not placebo (-46 ± 116 mg/dL, p = .878). Results for triglycerides were similar (25 ± 34 mg/dL, p =.045, and 7 ± 29 mg/dL, p = .464). Fasting low-density lipoprotein (LDL) levels were higher after salsalate (-10 ± 12 mg/dL, p = .025) but not placebo (2 ± 9 mg/dL, p = .403) treatment. Inflammatory markers were largely unchanged. Conclusion: In this pilot trial, descriptive values indicate that salsalate decreased fasting and PP glucose response to fast-food meal challenge at regular intervals in persons with tetraplegia. Positive effects were also seen for some lipid but not for inflammatory response markers. Given the relatively "healthy" metabolic profiles of the participants, it is possible that salsalate's effects may be greater and more consistent in people with less favorable metabolic milieus.

'White Cord Syndrome': A Rare Catastrophic Complication Following Anterior Cervical Discectomy and Fusion.

Background: 'White-cord syndrome' is an extremely rare entity following decompression of cervical cord in which post-operative reperfusion injury results in worsening of patient's neurology and MRI reveals signal changes in spinal cord in absence of cord compression. We wish to report a case of 'white-cord syndrome' following a 'routine' ACDF. Case Description: A 39-year-old woman with paresthesias and spastic quadriparesis was found to have C5-C6 PIVD on MRI. ACDF was performed at C5-C6, after which worsening of quadriparesis was noted, for which intravenous high-dose steroids were started. An urgent MRI was done, which revealed findings of white-cord syndrome, without compression on underlying cord. With conservative management, her ASIA grade improved from C to D and the features of white-cord syndrome disappeared on follow-up imaging. Conclusion: It is important for surgeons and patients to be aware of this rare but potentially catastrophic entity as this needs to be discussed while taking consent for surgery.

Pulse corticosteroids for the management of extensive CNS tuberculosis presenting with acute-onset quadriparesis.

Myelopathy in central nervous system tuberculosis is notorious for poor outcomes, determined by the severity of inflammation and cord level involved. Acute-onset quadriplegia or paraplegia in these cases represents a neuro-emergency. We report a young female with disseminated tuberculosis who presented with acute onset flaccid quadriparesis with loss of bladder and bowel function. Imaging helped identify the extensive involvement of the neuraxis. We propose that, in addition to anti-tubercular therapy, high-dose corticosteroids such as pulse methylprednisolone may result in a meaningful improvement and show greater rapidity of response in cases of severe central nervous system inflammation such as arachnoiditis or myelopathy.

A severe case of non-infective myositis six weeks post intramuscular injections of Onabotulinum toxin A (Botox) in a young man with tetraplegia: case report.

INTRODUCTION: Myositis of unknown aetiology might be a very rare complication of intramuscular injections of onabotulinum toxin A (Botox) for spasticity treatment. CASE PRESENTATION: We describe a case of significant myositis of unknown aetiology in a 17-year-old man, who was admitted for rehabilitation 4 months after his initial spinal cord injury (SCI) as a result of a mountain bike accident. He has an incomplete tetraplegia, C4 AIS B international Standards for Neurological Classification for Spinal Cord Injury (ISNCSCI) [1] due to C5 vertebra 3 column fracture [2]. He had severe spasticity of his lower limb muscles treated with Botox, following which, he required two acute hospital transfers for diagnosis and management of myositis. DISCUSSION: This is a severe unusual presentation of myositis caused by intramuscular botulinum toxin for treatment of spasticity, in the frequent setting of spasticity where intramuscular botulinum toxin injections are routinely used.

Autonomic dysreflexia in a case of radiation myelopathy and cisplatin-induced polyneuropathy.

INTRODUCTION: While autonomic dysreflexia caused by severe spinal cord lesions can be life-threatening, relevant reports on non-traumatic spinal lesions are rare. Furthermore, modes of innervation of the supraspinal inhibitory pathways at each spinal sympathetic segment remain unknown. Herein, I report the case of a patient with autonomic dysreflexia and radiation myelopathy. The laterality of autonomic dysreflexia was investigated with special reference to the sudomotor function. CASE PRESENTATION: A 51-year-old man with a history of epipharynx carcinoma, radiotherapy, and cisplatin chemotherapy was referred for the evaluation of autonomic function. He was ambulant but displayed spastic tetraparesis, areflexia of the extremities, sensory disturbance below C4 dermatome, dysuria, and impotence. Spinal magnetic resonance imaging demonstrated a cervical lesion involving the lateral portion of C2-C5, bilaterally. The thermal sweating test showed that sweating was lower on the left side of the face and neck, left shoulder, and arm than the corresponding parts on the right side. The rest of the body was anhidrotic. Sweating due to autonomic dysreflexia was symmetric, but more abundant on the left side of the face. Acetylcholine-induced sweating was markedly reduced on the left leg. DISCUSSION: This might be the first documentation of autonomic dysreflexia observed in a patient with radiation myelopathy. The present observations suggested that the supraspinal inhibitory pathway to spinal preganglionic neurons may descend on the same side as thermal sudomotor facilitatory pathways at the cervical level. Furthermore, autonomic dysreflexia was more prominent in the standing position suggesting that the pressure stimulus might enhance autonomic dysreflexia.

Adrenoleukodystrophy presenting as glue sniffing.

Adrenoleukodystrophy classically presents in childhood with bronze skin, spastic tetraparesis, dysphagia, behavioural abnormalities and adrenal insufficiency. However, atypical presentations are known. Here we report an adolescent with adrenoleukodystrophy who first sought medical attention for glue sniffing.

Rituximab in refractory chronic inflammatory demyelinating polyneuropathy.

INTRODUCTION: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a disorder in which early effective treatment is important to minimize disability from axonal degeneration. It has been suggested that some patients with CIDP may benefit from rituximab therapy, but there is no definitive evidence for this. METHODS: Baseline and post-rituximab-therapy neuromuscular Medical Research Council (MRC) sum scores, Inflammatory Neuropathy Cause and Treatment (INCAT) disability score, and functional status were assessed in 11 patients with refactory CIDP. RESULTS: The MRC sum score, INCAT disability score, and functional status improved in all patients after rituximab therapy. DISCUSSION: Our study provides evidence of the efficacy of rituximab therapy in at least some patients with CIDP. A placebo-controlled study to assess the effectiveness of rituximab therapy in CIDP with and without nodal antibodies is required to identify disease markers that predict responsiveness.

Palliative Sedation via Intraosseous Vascular Access: A Safe and Feasible Way to Obtain a Vascular Access End of Life.

Intraosseous (IO) access is normally reserved for emergencies and critical care conditions when venous cannulation is not possible. Nonetheless, we present a case of IO insertion to a 56-year-old man, tetraplegic for many years due to progressive spinal muscular atrophy and with refractory suffering. The IO access was used for palliative sedation with propofol in a home care setting. The patient died after 11 days of palliative care, of which the last 4 days were with palliative sedation using an IO cannula as a vascular access. No complications were noted from this route of administration. We advocate the use of IO access in the palliative care of terminal ill patients when a venous cannulation is not possible.

Severe CNS angiostrongyliasis in a young marine: a case report and literature review.

Angiostrongylus cantonensis is the most common cause of eosinophilic meningitis worldwide. Infection typically occurs through ingestion of undercooked molluscs or vegetables contaminated by infective larvae. Endemic regions were previously limited to southeast Asia and the Pacific basin; however, this parasite is seeing an alarming increase in global distribution with reported cases in more than 30 countries, including several states in the USA. Although infection typically results in meningitis, a broad spectrum of CNS involvement and severity is emerging as diagnostic methods (such as real-time PCR) continue to improve diagnosis. In this Grand Round, we report a case of a 20-year-old active duty US marine serving in Okinawa, Japan, afflicted with severe CNS angiostrongyliasis marked by radiculomyelitis with quadriparesis, hyperaesthesia, and urinary retention. We present this case to highlight that no clear guidelines exist for the treatment of severe CNS angiostrongyliasis and provide our consensus recommendation that treatment algorithms include use of dual corticosteroids plus anthelmintics when radicular symptoms are present. In this Grand Round we review the clinical features, epidemiology, advances to diagnostic techniques, and available data on current treatment options for CNS angiostrongyliasis. This diagnosis should be highly considered in the differential diagnosis of a patient presenting with meningeal symptoms, paraesthesia or hyperaesthesia, and CSF eosinophilia so that treatment can be started early, which is particularly important in children, because of their increased risk of severe disease and mortality. We recommend combined therapy with albendazole and prednisolone, with consideration for increased steroid dosing in severe cases.

Locked-in syndrome responding to thrombolytic therapy.

Locked-in syndrome (LIS) is an exceedingly rare condition that has been described as a fate worse than death. Unfortunately, exam findings can be subtle and imaging is poorly sensitive, often leading to a delay in diagnosis. We present a case of a 70-year-old female who presented to our emergency department after developing respiratory distress followed by sudden unresponsiveness. She was diagnosed with LIS and had an immediate and remarkable improvement after administration of tissue plasminogen activator (TPA). Patients presenting with sudden onset altered mental status require a very careful physical exam, even if deemed comatose, and should be considered for emergent imaging for stroke. Fortunately, our patient recovered well and was discharged home in good condition.

Normalization of disrupted clock gene expression in males with tetraplegia: a crossover randomized placebo-controlled trial of melatonin supplementation.

STUDY DESIGN: Crossover double blind, randomized placebo-controlled trial. OBJECTIVES: Circadian oscillators are located both in the brain and in peripheral organs. Melatonin, the main brain-derived hormone governing circadian variations, is highly associated with daylight patterns. However, in subjects with tetraplegia the melatonin levels are blunted. Here we studied peripheral oscillators in peripheral blood mononuclear cells (PBMCs) in males with tetraplegia by examining how exogenous melatonin may influence the expression of clock gene mRNAs. SETTING: Sunnaas Rehabilitation Hospital, Nesoddtangen, Norway. METHODS: Six males with tetraplegia received 2 mg of melatonin or placebo 4 days before the study period. We also included six able-bodied men sleeping or kept awake during the night. Plasma samples were collected four times during a 24-h period. The mRNA expression levels of the clock genes PER1, PER2, BMAL1, and REV-ERBα were quantified in PBMCs using quantitative RT-PCR. RESULTS: The mRNA expression levels of PER-1 and -2 and REV-ERBα were increased at 04:00 h compared with the able-bodied controls (p < 0.05). Melatonin supplementation changed mRNA peak-time toward the time of supplementation. CONCLUSIONS: Several peripheral clock genes displayed distorted expression levels in tetraplegia. Supplementation with melatonin changed the mRNA expression levels of these genes toward those observed among able-bodied. SPONSORSHIP: Financial support was provided from the Throne Holst Foundation, Sunnaas Rehabilitation hospital and the University of Ferrara (FAR2016).

First-in-Man Intrathecal Application of Neurite Growth-Promoting Anti-Nogo-A Antibodies in Acute Spinal Cord Injury.

BACKGROUND: Neutralization of central nervous system neurite growth inhibitory factors, for example, Nogo-A, is a promising approach to improving recovery following spinal cord injury (SCI). In animal SCI models, intrathecal delivery of anti-Nogo-A antibodies promoted regenerative neurite growth and functional recovery. OBJECTIVE: This first-in-man study assessed the feasibility, safety, tolerability, pharmacokinetics, and preliminary efficacy of the human anti-Nogo-A antibody ATI355 following intrathecal administration in patients with acute, complete traumatic paraplegia and tetraplegia. METHODS: Patients (N = 52) started treatment 4 to 60 days postinjury. Four consecutive dose-escalation cohorts received 5 to 30 mg/2.5 mL/day continuous intrathecal ATI355 infusion over 24 hours to 28 days. Following pharmacokinetic evaluation, 2 further cohorts received a bolus regimen (6 intrathecal injections of 22.5 and 45 mg/3 mL, respectively, over 4 weeks). RESULTS: ATI355 was well tolerated up to 1-year follow-up. All patients experienced ≥1 adverse events (AEs). The 581 reported AEs were mostly mild and to be expected following acute SCI. Fifteen patients reported 16 serious AEs, none related to ATI355; one bacterial meningitis case was considered related to intrathecal administration. ATI355 serum levels showed dose-dependency, and intersubject cerebrospinal fluid levels were highly variable after infusion and bolus injection. In 1 paraplegic patient, motor scores improved by 8 points. In tetraplegic patients, mean total motor scores increased, with 3/19 gaining >10 points, and 1/19 27 points at Week 48. Conversion from complete to incomplete SCI occurred in 7/19 patients with tetraplegia. CONCLUSIONS: ATI335 was well tolerated in humans; efficacy trials using intrathecal antibody administration may be considered in acute SCI.

Hypercapnia Caused by a Therapeutic Dosage of Pregabalin in a Tetraplegic Patient With Cervical Spinal Cord Injury.

Pregabalin is often used for the treatment of neuropathic pain in patients with spinal cord injury (SCI). We reported a patient with C5 [S(C5/C6)] ASIA Impairment Scale C SCI due to cervical myelopathy who presented CO2 retention when taking a therapeutic dosage of pregabalin. An 88-year-old patient with cervical SCI was transferred to the department of physical medicine and rehabilitation. When he had transferred, his neuropathic pain had been treated with 150-mg pregabalin per day (75 mg twice a day); however, he still exhibited severe neuropathic pain with a Numeric Pain Rating Scale score of 7 to 8. Dosage for the pregabalin increased from 150 mg/d (75 mg twice a day) to 225 mg/d (150 mg at morning and 75 mg at dinner). That afternoon, he presented drowsiness and confusion, and arterial blood gas analysis (ABGA) demonstrated respiratory acidosis with CO2 retention; pH, 7.312; PaCO2, 62.8 mm Hg; PaO2,58.9 mm Hg; HCO3 concentration, 30.8 mmol/L; base excess, 3.2 mmol/L; and oxygen saturation, 90.4%. Finally, he required tracheal intubation and ventilation. After 6 weeks, the patient was transferred to a general ward, and the follow-up ABGA and end-tidal CO2 showed normal range with the discontinuation of pregabalin. We demonstrated CO2 retention via ABGA in a patient with SCI due to cervical myelopathy who developed hypercapnia after taking a therapeutic dose of pregabalin. Physicians should pay particular attention to CO2 retention when prescribing a therapeutic dosage of pregabalin in a patient with cervical SCI.

Asymmetric Acute Motor Axonal Neuropathy With Unilateral Tongue Swelling Mimicking Stroke.

A 60-year-old man presented with acute onset of left hemiparesis and left hypoglossal nerve palsy with ipsilateral tongue swelling. He then progressed to tetraparesis in a few days. Cerebrospinal fluid showed cell protein dissociation. A nerve conduction study showed motor axonal neuropathy with sensory sparing. A subsequent blood test revealed anti-GD1b IgG antibody positivity. He was diagnosed to have acute motor axonal neuropathy (AMAN) and treated with a course of intravenous immunoglobulin with slow improvement. This is probably the first AMAN with asymmetrical presentation mimicking stroke reported in the literature in detail. The anti-GD1b IgG antibody is also not commonly associated with AMAN.

Intrathecal baclofen withdrawal: A rare cause of reversible cardiomyopathy.

Baclofen is commonly used to treat spasticity of central etiology. Unfortunately, a potentially lethal withdrawal syndrome can complicate its use. This is especially true when the drug is administered intrathecally. There are very few cases of baclofen withdrawal leading to reversible cardiomyopathy described in the literature. The authors present a patient with a history of chronic intrathecal baclofen use who, in the setting of acute baclofen withdrawal, develops laboratory, electrocardiogram, and echocardiogram abnormalities consistent with cardiomyopathy. Upon reinstitution of intrathecal baclofen, the cardiomyopathy and associated abnormalities quickly resolve. Although rare, it is crucial to be aware of this reversible cardiomyopathy to ensure its prompt diagnosis and treatment.