Sleep Treatments in Disorders of Consciousness: A Systematic Review

Sleep disorders are among the main comorbidities in patients with a Disorder of Consciousness (DOC). Given the key role of sleep in neural and cognitive functioning, detecting and treating sleep disorders in DOCs might be an effective therapeutic strategy to boost consciousness recovery and levels of awareness. To date, no systematic reviews have been conducted that explore the effect of sleep treatments in DOCs; thus, we systematically reviewed the existing studies on both pharmacological and non-pharmacological treatments for sleep disorders in DOCs. Among 2267 assessed articles, only 7 were included in the systematic review. The studies focused on two sleep disorder categories (sleep-related breathing disorders and circadian rhythm dysregulation) treated with both pharmacological (Modafinil and Intrathecal Baclofen) and non-pharmacological (positive airway pressure, bright light stimulation, and central thalamic deep brain stimulation) interventions. Although the limited number of studies and their heterogeneity do not allow generalized conclusions, all the studies highlighted the effectiveness of treatments on both sleep disorders and levels of awareness. For this reason, clinical and diagnostic evaluations able to detect sleep disorders in DOC patients should be adopted in the clinical routine for the purpose of intervening promptly with the most appropriate treatment.

P.154 Subcutaneous intrathecal catheter and port implants for administration of Nusinersen in patients with Spinal Muscular Atrophy

Background: Until recently, no effective treatment was available for spinal muscular atrophy (SMA). In 2017, Health Canada approved intrathecal Nusinersen a medication that prevents degeneration of the motor neurons in the spinal cord. The administration is intrathecally most commonly via lumbar puncture (LP) to have a direct effect on the motor neurons of the spinal cord. Many older patients with SMA and concomitant spinal deformities present technical challenges to access the thecal sac. Different routes have been described for delivery of the medication whoever these techniques may require sedation, are associated with radiation exposure, and demand experience personnel. Methods: A new surgical technique has been proposed to overcome these obstacles by combining two Health Canada approved devices: 1) an intrathecal catheter designed for intrathecal baclofen pumps and 2) an implantable subcutaneous port designed for intravascular medication administration Results: We describe the technical nuances and outline the clinical outcomes of six patients with complex spine deformities who have undergone such an implant for administration of Nusinersen. Conclusions: We discuss the benefits of the procedure which includes: 1) administration in the outpatient setting without sedation, 2) avoidance of costly imaging and experienced personnel, and 3) placement of the catheter in the cervicothoracic junction.

Systemic and intrathecal baclofen produce bladder antinociception in rats

Background Baclofen, a clinically available GABAB receptor agonist, produces non-opioid analgesia in multiple models of pain but has not been tested for effects on bladder nociception. Methods A series of experiments examined the effects of systemic and spinally administered baclofen on bladder nociception in female anesthetized rats. Models of bladder nociception included those which employed neonatal and adult bladder inflammation to produce bladder hypersensitivity. Results Cumulative intraperitoneal dosing (1–8 mg/kg IP) and cumulative intrathecal dosing (10–160 ng IT) of baclofen led to dose-dependent inhibition of visceromotor responses (VMRs) to urinary bladder distension (UBD) in all tested models. There were no differences in the magnitude of the analgesic effects of baclofen as a function of inflammation versus no inflammation treatments. Hemodynamic (pressor) responses to UBD were similarly inhibited by IT baclofen as well as UBD-evoked excitatory responses of spinal dorsal horn neurons. The GABAB receptor antagonist, CGP 35,348, antagonized the antinociceptive effects of IT baclofen on VMRs in all tested models but did not affect the magnitude of the VMRs by itself suggesting no tonic GABAB activity was present in this preparation. Tolerance to a seven day continuous IT infusion of baclofen was not observed. Conclusions These data provide support for a clinical trial of baclofen as a non-opioid treatment of human bladder pain.

Prepontine placement of an intrathecal baclofen pump catheter for treatment of dystonia

Background: Cerebral palsy with medically refractory spasticity and dystonia is a condition that often benefits from intrathecal baclofen pump therapy to treat these symptoms. In this case report, an intracranial baclofen catheter was placed in the prepontine space to improve withdrawal symptoms in a patient unable to undergo new lumbar catheter placement due to infection. Case Description: A 22-year-old female with past medical history of cerebral palsy presented with baclofen pump failure and was unable to undergo placement of a new lumbar baclofen catheter due to an infection in her lower back precluding safe and efficacious catheter placement. It was decided the patient would benefit from intrathecal baclofen administered in the prepontine space as a means to avoid a lumbar catheter and thus bypass this prior infection site. An endoscopic third ventriculostomy (ETV) was performed with the endoscope and the distal end of the baclofen pump catheter was fed through this ETV into the prepontine space. Placement in the prepontine space was confirmed by a follow-up head computed tomography. There was a significant improvement in autonomic symptoms and spasticity. By postoperative day 5, the patient was surgically and medically cleared for discharge. Conclusion: In cases of severe baclofen withdrawal due to dysfunctional pumps, immediate reversal is preferred but may not be feasible due to factors such as infection. This case report has demonstrated that prepontine catheter placement can be effective for the administration of baclofen to reverse withdrawal symptoms in these types of patients.