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.

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).

Respiratory Function Under Intrathecal Baclofen Therapy in Patients With Spastic Tetraplegia.

OBJECTIVES: Intrathecal baclofen (ITB) therapy is an effective treatment for patients with severe spasticity. However, the effect of ITB therapy on respiratory function has not been reported in detail. In this study we quantitatively analyzed the effects of ITB on the respiratory function of patients with spastic tetraplegia. METHODS: We retrospectively reviewed 23 patients who were administrated ITB therapy from January 2009 to December 2012. Six of these 23 patients, who had spastic tetraplegia and were able to undergo spirometric testing, were included this study. The spasticity derived from cervical spinal cord injury in four patients and cerebral palsy (CP) in two patients. Patients' Ashworth Scale scores and spirometer measurements obtained before and 1-6 months after the start of ITB therapy were evaluated and compared. RESULTS: Before ITB therapy, %FVC of all six patients was below 80%, and a restrictive respiratory disorder was diagnosed in five patients and a combined respiratory disorder in one patient. Ashworth Scale scores for both the lower and upper extremities improved significantly with ITB therapy. Forced vital capacity (FVC), %FVC, and forced expiratory volume at one sec also improved significantly with ITB therapy. CONCLUSIONS: Respiratory disorders were indeed present in our SCI and CP patients with spastic tetraplegia, and the respiratory function of these patients improved with ITB therapy. Our results suggest that ITB therapy is safe and efficacious in patients with spastic tetraplegia and respiratory dysfunction.

Hypogonadotropic Hypogonadism in a Boy with Myopathy.

Hypogonadism is seldom seen together with myopathy, although testosterone contributes to muscle strength. We present here a rare case of hypogonadotropic hypogonadism with myopathy in a 20 year old male. He had flaccid quadriparesis with raised creatinine phosphokinase. Hormone assays revealed low testosterone as well as low luteinising hormone and follicle stimulating hormone levels. Tests to exclude androgen deficiency should be carried out in male patients with myopathy.

Unusual case of tetraparesis in a patient with systemic lupus erythematosus.

We describe the case of a 67-year-old Asian female patient suffering from severe systemic lupus erythematosus (SLE), including biopsy-proven glomerulonephritis, since the age of 40 who was admitted for tetraparesis. Neurological examination confirmed proximal muscular weakness, hypoesthesia and diminished tendon reflexes. The patient suffered from extremely severe Jaccoud's arthropathy. Magnetic resonance imaging (MRI) demonstrated severe narrowing of the upper spinal canal due to a soft tissue mass surrounding the odontoid process, assumed to be a synovial pannus, causing myelopathy. The patient was treated with three intravenous pulses of methylprednisolone with prompt and full clinical recovery. Follow-up MRI confirmed considerable regression of the pannus. Inflammatory transverse myelopathy is the most common explanation for para/tetraparesis in SLE. However, in this case, the symptoms were caused by atlantoaxial synovitis, which is more typical for rheumatoid arthritis.

Pyomyositis Causing Temporary Quadriparesis During Induction Therapy for Acute Lymphoblastic Leukemia: Case Report and Review of the Literature.

Pyomyositis (PM) is a purulent infection of skeletal muscle. It is often associated with immunosuppression in temperate climates. Herein, we report a case of PM causing temporary quadriparesis in a 14-year-old girl undergoing induction therapy for acute lymphoblastic leukemia and we review the reported pediatric cases associated with induction therapy for hematologic malignancies. Early symptoms of PM can be mistaken for the side effects of chemotherapeutic agents. Greater awareness of the clinical picture of PM will aid in early diagnosis and treatment. With appropriate medical therapy and timely abscess drainage, morbidity and mortality is greatly reduced.

Intrathecal baclofen: effects on spasticity, pain, and consciousness in disorders of consciousness and locked-in syndrome.

Disorders of consciousness (DOCs) include coma, vegetative state (VS), and minimally conscious state (MCS). Coma is characterized by impaired wakefulness and consciousness, while VS and MCS are defined by lacking or discontinuous consciousness despite recovered wakefulness. Conversely, locked-in syndrome (LIS) is characterized by quadriplegia and lower cranial nerve paralysis with preserved consciousness. Intrathecal baclofen (ITB) is a useful treatment to improve spasticity both in patients with DOCs and LIS. Moreover, it supports the recovery of consciousness in some patients with VS or MCS. The precise mechanism underlying this recovery has not yet been elucidated. It has been hypothesized that ITB may act by reducing the overload of dysfunctional sensory stimuli reaching the injured brain or by stabilizing the imbalanced circadian rhythms. Although the current indication of ITB is the management of severe spasticity, its potential use in speeding the recovery of consciousness merits further investigation.

Medication profile and polypharmacy in adults with pediatric-onset spinal cord injury.

STUDY DESIGN: Cross-sectional survey. OBJECTIVES: To describe the medications taken by individuals who had sustained a spinal cord injury (SCI) in childhood or adolescence (age <19 years) and to report the prevalence of polypharmacy and its association with demographic, injury-related and psychosocial factors. SETTING: Community. METHODS: Structured interviews of adults with pediatric-onset SCI. Routine medications and secondary health conditions (SHCs) experienced were recorded. Polypharmacy was defined as the concomitant use of five or more different types of medications. Bivariate analyses and multiple regression models were conducted to determine associations between polypharmacy and demographic factors, injury-related factors, number of SHCs and psychosocial outcomes (FIM, SF-12v2 Health Survey, CHART, PHQ-9). RESULTS: A total of 159 participants (male, 63%; tetraplegia, 59%) with mean age 35.0±6.2 years (range, 26.7-50.9 years) were included. Most common routine medications were muscle relaxants (50.3%), bladder medications (48.5%), bowel agents (41.5%), analgesics (26.4%) and antidepressants (16.9%). Polypharmacy was present in 30.8% (n, 49) and was more prevalent in those with tetraplegia (40.2% vs 17.9%; P=0.003). Participants with polypharmacy were older, had lower FIM, CHART and SF-12v2 scores, and higher PHQ-9 scores. Regression models indicate the total number of SHCs, time since injury and tetraplegia to be significant positive predictors of polypharmacy. CONCLUSION: Duration of SCI and SHCs are risk factors for polypharmacy in this population of adults with SCI. Measures should be taken to prevent the occurrence of SHCs throughout adulthood so as to prevent the potentially adverse physiological effects and psychosocial outcomes associated with polypharmacy.

Circadian rhythms of hemostatic factors in tetraplegia: a double-blind, randomized, placebo-controlled cross-over study of melatonin.

STUDY DESIGN: This is a double-blind, randomized, placebo-controlled cross-over study of melatonin in complete tetraplegia. OBJECTIVES: Tetraplegic patients have an increased risk of venous thrombosis despite prophylaxis, blunted variations in melatonin and altered circadian variation of several hemostatic markers. To examine whether melatonin could modify the regulation of hemostasis, we measured plasma melatonin and several markers of hemostasis in tetraplegic subjects with or without melatonin supplement. SETTING: The study was conducted in the Section for Spinal Cord Injury, Sunnaas Hospital, Nesoddtangen, Norway. METHODS: Six subjects with long-standing complete tetraplegia were included in this cross-over study with 2 mg of melatonin or placebo given 4 days before sampling. We also included six able-bodied men without any intervention. Plasma samples were then collected frequently during a 24-h awake/sleep cycle. The plasma concentrations of melatonin and the various markers were analyzed using linear mixed models. RESULTS: The 24-h profiles of prothrombin fragment 1+2 and von Willebrand factor, but not D-dimer, activated FVII, tissue factor pathway inhibitor and plasminogen activator inhibitor type 1, differed (P<0.05) between tetraplegic patients and able-bodied subjects. The absolute plasma concentration of activated FVII was higher (P<0.05) among the able-bodied compared with the tetraplegic groups. Supplementation of melatonin had no impact on these findings. CONCLUSIONS: We found differences in circadian variation of several hemostatic markers between able-bodied and tetraplegics. These differences were apparently unrelated to fluctuations in the melatonin concentrations, suggesting little or no role of melatonin in the regulation of hemostasis in tetraplegia. SPONSORSHIP: Financial support was provided from the Throne Holst Foundation.

Dexmedetomidine for acute baclofen withdrawal.

BACKGROUND: Intrathecal baclofen is widely accepted as a treatment option for severe spasticity through its γ-Aminobutyric acid-B (GABAB ) agonist properties. Abrupt cessation can lead to severe and life-threatening withdrawal characterized by altered mental status, autonomic dysreflexia, rigidity, and seizures. This symptomatic presentation is similar to alcohol withdrawal, which is mediated by modification of GABAA expression. Use of the α2-adrenergic agonist dexmedetomidine for the treatment of ethanol withdrawal has been widely reported, raising the question of its potential role in baclofen withdrawal. We present a case of the successful treatment of acute severe baclofen withdrawal with a dexmedetomidine infusion. METHODS: A 15-year-old patient with spastic quadriparesis and cerebral palsy underwent unexpected removal of his baclofen pump due to an infection that was encountered during a planned pump revision. Following removal, he was placed on high dose enteral baclofen every 6 h. Despite further benzodiazepine supplementation, he had progressive hemodynamic instability, severe rebound spasticity, and intermittent spontaneous clonus consistent with baclofen withdrawal. A dexmedetomidine infusion was titrated to a peak dose of 16 mcg per hour with successful treatment of withdrawal symptoms. RESULTS: The patient became normotensive without tachycardia. Tone and agitation improved. CONCLUSION: Dexmedetomidine is to our knowledge a previously unreported option for treatment of acute severe baclofen withdrawal. We report a case of safe and efficacious use in a patient with spastic quadriparesis on chronic intrathecal baclofen. Scientifically rigorous comparison with other options remains to be performed.

[Effectiveness of continuous infusion of tizanidine (Ternelin) via a feeding tube for patients with the mixed type of tetraplegia].

OBJECTIVE: Severe muscle hypertonia in patients with the mixed type of tetraplegia may be associated with significant deterioration in the quality of life of the patients. Intermittent use of oral muscle relaxant drugs, for example, Tizanidine (Ternelin), which is a fast-acting muscle relaxant, can provide relief from the severe hypertonia in these patients, but only for short durations. METHODS: We conducted a retrospective study of the effect of continuous infusion of tizanidine via a feeding tube on the severe systemic muscle hypertonia in patients with the mixed type of tetraplegia. We mixed tizanidine with milk or other enteral nutrients and administered the mixture via a naso-duodenal tube at a constant infusion rate several hours to 5 patients with the mixed type of tetraplegia showing severe uncontrolled systemic hypertonia under intermittent treatment with oral muscle relaxant drugs. RESULTS: Significant relief from the systemic muscle hypertonia was obtained in 4 of the 5 patients with improvement of the quality of life of the patients, e. g., they could get adequate sleep. There were no serious side effects in any of the cases. CONCLUSION: We consider that continuous infusion of tizanidine via a feeding tube would be useful for the treatment of severe systemic hypertonia in patients in whom the symptom cannot be adequately controlled by intermittent use of oral muscle relaxant drugs.

Selective effects of baclofen on use-dependent modulation of GABAB inhibition after tetraplegia.

Baclofen is a GABAB receptor agonist commonly used to relief spasticity related to motor disorders. The effects of baclofen on voluntary motor output are limited and not yet understood. Using noninvasive transcranial magnetic and electrical stimulation techniques, we examined electrophysiological measures probably involving GABAB (long-interval intracortical inhibition and the cortical silent period) and GABAA (short-interval intracortical inhibition) receptors, which are inhibitory effects mediated by subcortical and cortical mechanisms. We demonstrate increased active long-interval intracortical inhibition and prolonged cortical silent period during voluntary activity of an intrinsic finger muscle in humans with chronic incomplete cervical spinal cord injury (SCI) compared with age-matched controls, whereas resting long-interval intracortical inhibition was unchanged. However, long-term (~6 years) use of baclofen decreased active long-interval intracortical inhibition to similar levels as controls but did not affect the duration of the cortical silent period. We found a correlation between signs of spasticity and long-interval intracortical inhibition in patients with SCI. Short-interval intracortical inhibition was decreased during voluntary contraction compared with rest but there was no effect of SCI or baclofen use. Together, these results demonstrate that baclofen selectively maintains use-dependent modulation of largely subcortical but not cortical GABAB neuronal pathways after human SCI. Thus, cortical GABA(B) circuits may be less sensitive to baclofen than spinal GABAB circuits. This may contribute to the limited effects of baclofen on voluntary motor output in subjects with motor disorders affected by spasticity.

Sleep disruption in tetraplegia: a randomised, double-blind, placebo-controlled crossover trial of 3 mg melatonin.

STUDY DESIGN: Randomised, double-blind, placebo-controlled crossover trial of melatonin supplementation to people with complete tetraplegia. OBJECTIVES: To investigate the effect that 3 mg melatonin supplementation has on objective and subjective sleep, quality of life and mood of people living with complete tetraplegia. SETTING: Austin Hospital Sleep Laboratory and participants' homes, Melbourne, Victoria, Australia. METHODS: Two week run-in followed by 3 week nightly administration of 3 mg melatonin or placebo, 2-week washout and further 3 week administration of the opposite treatment. Four testing sessions were conducted; the last nights of the run-in, treatment and washout periods. Testing sessions involved recording full polysomnography, completing a questionnaire battery and collecting urine and blood samples. The questionnaires assessed mood, sleep symptoms and health-related quality of life, and the urine and plasma samples assayed 6-sulphatoxymelatonin (aMT6s) and melatonin levels, respectively. A sleep diary was completed throughout the study. RESULTS: Eight participants (mean (s.d.): age 49.5 years (16), postinjury 16.9 years (7.1)) were recruited in which seven concluded the protocol. Endogenous-circulating melatonin was significantly higher (P < or = 0.01) following melatonin (urine: 152.94 µg h(-1) (74.51), plasma: 43,554.57 pM (33,527.11)) than placebo (urine: 0.86 µg h(-1) (0.40), plasma: 152.06 pM (190.55)). Subjective sleep improved significantly following melatonin specifically for duration of sleep per night and psychological wellbeing. Objective sleep showed a significant increase in light sleep with melatonin, with all other sleep parameters being unchanged. CONCLUSION: These results suggest that increasing melatonin in people with complete tetraplegia is beneficial, especially for subjective sleep. Investigation of the pharmacokinetics of melatonin metabolism in this population is warranted. SPONSORSHIP: This project is proudly supported by the Transport Accident Commission.

Ultrasound-guided refilling of an intrathecal baclofen pump--a case report.

INTRODUCTION: Refilling intrathecal baclofen (ITB) pumps can be difficult because many patients gain excessive weight after implantation due to their reduced expenditure of energy on muscle spasticity. METHODS: We report a case of a 12-year-old girl with spastic quadriplegia who gained 20 lbs after pump implantation. It was necessary to identify the access port of her pump by ultrasonography during drug refilling so as to avoid multiple needle punctures. RESULTS: The access port of the pump was readily visible by ultrasonography and stood out from other parts of the pump. CONCLUSION: Localisation of the access ports of ITB pumps by ultrasonography proved to be a feasible and easy technique for refilling the drug reservoir in patients with excessive weight gain and abundant subcutaneous fat after ITB therapy.

A retrospective chart review of heart rate and blood pressure abnormalities in veterans with spinal cord injury.

OBJECTIVE: Autonomic impairment may lead to increased prevalence of heart rate (HR) and blood pressure (BP) abnormalities in veterans with spinal cord injury (SCI). In addition, comorbid medical conditions and prescription medication use may influence these abnormalities, including bradycardia, and tachycardia, hypotension, hypertension as well as autonomic dysreflexia (AD), and orthostatic hypotension (OH). DESIGN: A retrospective review of clinical and administrative datasets in veterans with SCI and compared the prevalence rates between clinical values and ICD-9 diagnostic codes in individuals with tetraplegia (T: C1-C8), high paraplegia (HP: T1-T6), and low paraplegia (LP: T7 and below). RESULTS: The prevalence of clinical values indicative of a HR ≥ 80 beats per minute was higher in the HP compared to the LP and T groups. A systolic BP (SBP) ≤ 110 mmHg was more common in the T compared to the HP and LP groups, whereas the prevalence of a SBP ≥ 140 mmHg was increased in the LP compared to the HP and T groups. Diagnosis of hypertension was 39-60% whereas the diagnosis of hypotension was less than 1%. Diagnosis of AD and OH was highest in the T group, but remained below 10%, regardless of categorical lesion level. Antihypertensive medications were commonly prescribed (55%), and patients on these medications were less likely to have high BP. The odds ratio of higher SBP and DBP increased with age and body mass index (BMI). CONCLUSION: In veterans with SCI, the prevalence of HR and BP abnormalities varied depending on level of lesion, age, BMI, and prescription medication use.

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.

Neuroprotective therapy using granulocyte colony-stimulating factor for patients with worsening symptoms of compression myelopathy, Part 1: a phase I and IIa clinical trial.

OBJECTIVE: Based on the neuroprotective effects of granulocyte colony-stimulating factor (G-CSF) on experimental spinal cord injury, we initiated a clinical trial that evaluated the safety and efficacy of neuroprotective therapy using G-CSF for patients with worsening symptoms of compression myelopathy. METHODS: We obtained informed consent from 15 patients, in whom the Japanese Orthopaedic Association (JOA) score for cervical myelopathy decreased two points or more during a recent 1-month period. G-CSF (5 or 10 µg/kg/day) was intravenously administered for five consecutive days. We evaluated motor and sensory functions of the patients and the presence of adverse events related to G-CSF therapy. RESULTS: G-CSF administration suppressed the progression of myelopathy in all 15 patients. Neurological improvements in motor and sensory functions were obtained in all patients after the administration, although the degree of improvement differed among the patients. Nine patients in the 10-µg group (n=10) underwent surgical treatment at 1 month or later after G-CSF administration. In the 10-µg group, the mean JOA recovery rates 1 and 6 months after administration were 49.9±15.1 and 59.1±16.3%, respectively. On the day following the start of G-CSF therapy, the white blood cell count increased to more than 22,700 cells/mm3. It varied from 12,000 to 50,000 and returned to preadministration levels 3 days after completing G-CSF treatment. No serious adverse events occurred during or after treatment. CONCLUSION: The results indicate that G-CSF administration at 10 µg/kg/day is safe for patients with worsening symptoms of compression myelopathy and may be effective for their neurological improvement.