Safety and efficacy of ledipasvir/sofosbuvir with or without ribavirin in hepatitis C genotype 1 patients including those with decompensated cirrhosis who failed prior treatment with simeprevir/sofosbuvir.

BACKGROUND: Combination therapy of simeprevir (SIM)/sofosbuvir (SOF) is an approved treatment for hepatitis C genotype (gen) 1 with overall SVR12 rate of 85%-95%. The single tablet fixed-dose combination of ledipasvir (LDV)/SOF is also approved for gen 1 with sustained virologic response at 12 weeks (SVR12) rates ≥95%. No data are available on the efficacy of retreatment with LDV/SOF in patients who failed initial treatment with SIM/SOF. AIM: To evaluate the efficacy of retreatment with LDV/SOF ± ribavirin (RBV) in gen 1 patients who had previously failed treatment with SIM/SOF. METHODS: Data from a combined treatment cohort of 2 hepatology centres, which included patients previously treated with SIM/SOF ± RBV for 12 weeks but failed to achieve SVR and then underwent retreatment with LDV/SOF ± RBV, were analysed (n = 30). LDV/SOF ± RBV was administered for 12-24 weeks based on the discretion of the treating hepatologist. RESULTS: Of the 30 patients, 23 (77%) were male, 77% were Caucasian and 26 (87%) were gen 1a. 26 (86%) had cirrhosis, of which 16 (62%) had decompensated, Child's class B or C cirrhosis. Three patients were liver transplant recipients with recurrent hepatitis C. Overall, 27/30 (90%) achieved SVR. Treatment was well tolerated with 37% reporting no adverse events. The most common adverse events were fatigue, headache, insomnia and nausea. Two patients with Child's B cirrhosis required hospitalization during treatment for variceal haemorrhage and abdominal pain respectively. However, no treatment discontinuations or deaths occurred. CONCLUSION: Single tablet fixed-dose combination LDV/SOF ± RBV is efficacious and well tolerated in patients who previously failed treatment with SIM/SOF, including those with decompensated cirrhosis and recurrent hepatitis C following liver transplantation.

Tactile illusion perception in patients with central pain.

OBJECTIVE: To evaluate lemniscal pathways in patients with central pain (CP) by use of a novel tactile illusion (TI)-producing technique. PATIENTS AND METHODS: Somatosensory (SS) and TI testing was performed on the unaffected and affected wrists of 27 patients with unilateral central nervous system injury and unilateral CP. Data on TI testing-naive control subjects were used to adjust for a learning effect. RESULTS: Testing in CP patients with cervical and brainstem injuries revealed predominantly unchanged or decreased SS perception on the affected side compared with the unaffected side. The majority of cervical- and brainstem-injured subjects with CP had improved TI performance on the affected side compared with the unaffected side. All the thalamic-injured and most of the suprathalamic-injured CP patients had altered SS testing with either decreased or increased SS perception noted. In these same CP patients the majority had reduced TI perception on the affected side compared with the unaffected side. Unexpectedly, perseveration of numbers was noted in patients with Dejerine-Roussy syndrome, and expanded TI testing was performed to better define this observation. CONCLUSION: Cervical spinal cord-injured CP patients may have improved TI perception, whereas the majority of patients with supraspinal injuries and CP have reduced SS and TI perception. A unique sensory phenomenon of TI perseveration was observed in some patients with Dejerine-Roussy syndrome.

Methadone analgesia in cancer pain patients on chronic methadone maintenance therapy.

Methadone is currently best known for its use as the maintenance drug in opioid addiction. The main concern when using methadone for the treatment of pain is its long and unpredictable half-life, which is associated with the risk of delayed toxicity. This may result in side effects such as sedation and respiratory depression if careful titration and close observation of individual patient responses are not performed. For this reason, methadone is often viewed as a second line opioid, after other opioids with a more predictable dose-response have been tried. We report six patients with long-term exposure to methadone as a treatment for heroin dependency, who were also treated with methadone for cancer pain. The first five patients were at least partially refractory to the analgesic effects of opioids other than methadone. All six patients achieved analgesia without sedation or respiratory depression from aggressive upward methadone titration. Methadone analgesia can be considered early in the course of treatment of patients with chronic exposure to methadone who develop new or worsening pain requiring opioid therapy.

Reversible spastic paraparesis induced by high-dose intravenous methadone.

High doses of parenteral opioids can cause multifocal myoclonus and seizures. Spasticity has been reported in patients receiving intraspinal opioids. In this article, we describe a patient who developed reversible spastic paraparesis with prominent extensor spasms in the legs while receiving an infusion of intravenous methadone at 100 mg/hr. We discuss clinical presentation and possible pathophysiologic mechanisms of opioid side effects on the somatic motor system.

Tactile illusion-produced number perception in blind and sighted persons.

OBJECTIVE: To determine whether tactile receptive communication is possible in both sighted and blind persons through the use of a mechanical device that creates the perception of continuous contact through sequential points of vibration on the skin and whether the ability of these two groups differs. MATERIAL AND METHODS: The cohort consisted of 20 sighted and 20 blind subjects who had no prior exposure to a tactile communication device that produces a tactile illusion. Each subject was presented number sequences created by the tactile illusion in the form of single-digit, three-digit, and four-digit sequences, and the number of trials needed for correct identification was recorded. RESULTS: On average, the sighted subjects tended to identify the digit sequences sooner than did the blind subjects by almost one trial; however, this difference was not statistically significant. Younger subjects and female subjects also tended to identify the digit sequences sooner. Nevertheless, the overall correlation between age and number of trials across all replications was relatively minor. CONCLUSION: Tactile receptive communication is possible through the use of a mechanical device used to create tactile illusions. The tactile illusion of numbers is equally perceived by blind and sighted persons.

Pain in Tolosa-Hunt syndrome.

Tolosa-Hunt syndrome (THS) is a condition that includes recurrent attacks of retro-orbital, steady, and severe pain usually as the presenting symptom. Symptoms may include spontaneous recurrence of pain, chronic pain, and cranial nerve dysfunction that are responsive to steroid treatment. A patients with THS is described, with findings on craniotomy and biopsy, and the typical presentation of acute pain and recurrence of pain associated with response to steroid treatment. An overview of pain in this condition is presented.

The effects of postmortem delay on mu, delta and kappa opioid receptor subtypes in rat brain and guinea pig cerebellum evaluated by radioligand receptor binding.

Studies of human and animal central nervous system receptor degradation and measurement postmortem are important as human tissue can rarely be collected under ideal experimental conditions. Correlating the change in binding of opioid receptor subtypes over time will help define the conditions under which human studies may be valid. The present study was designed to investigate the rate at which opioid receptor subtypes degrade postmortem. Brains from rats or cerebelli from guinea pigs were kept at 22 degrees C or 4 degrees C at times from zero to 24 hours to simulate two common human collection techniques; room temperature and morgue refrigeration. Tissue homogenates from these brains were analysed for mu1, mu2, delta, kappa1 and kappa3 opioid receptor binding using standard radioligand binding techniques. At room temperature mu1, mu2 and delta opioid receptor binding was reduced between 6 and 12 hours, whereas kappa1 and kappa3 binding was reduced after 24 hours. At 4 degrees C mu1, mu2, delta, kappa1 and kappa3 binding remained constant over the 24 hour period.

Symbol recognition produced by points of tactile stimulation: the illusion of linear continuity.

OBJECTIVE: To determine whether tactile receptive communication is possible through the use of a mechanical device that produces the phi phenomenon on the body surface. DESIGN: Twenty-six subjects (11 blind and 15 sighted participants) were tested with use of a tactile communication device (TCD) that produces an illusion of linear continuity forming numbers on the dorsal aspect of the wrist. Recognition of a number or number set was the goal. MATERIAL AND METHODS: A TCD with protruding and vibrating solenoids produced sequentially delivered points of cutaneous stimulation along a pattern resembling numbers and created the illusion of dragging a vibrating stylet to form numbers, similar to what might be felt by testing for graphesthesia. RESULTS: Blind subjects recognized numbers with fewer trials than did sighted subjects, although all subjects were able to recognize all the numbers produced by the TCD. Subjects who had been blind since birth and had no prior tactile exposure to numbers were able to draw the numbers after experiencing them delivered by the TCD even though they did not recognize their meaning. CONCLUSION: The phi phenomenon is probably responsible for the illusion of continuous lines in the shape of numbers as produced by the TCD. This tactile illusion could potentially be used for more complex tactile communications such as letters and words.

Radiation-induced meningioma following radiation therapy for pituitary adenoma. Case report.

The authors report the long-term result of treatment of a presumed pituitary adenoma with external-beam radiation therapy, which appears to be the development of a radiation-induced meningioma. Of the post radiation neoplasms that have been reported, meningiomas constitute a large proportion of these lesions.

Central pain: diagnosis and treatment strategies.

The pathophysiology of central pain (CP) remains poorly understood. The paucity of objective findings on clinical examination of some of these patients can add to the difficulty in establishing a concrete diagnosis of CP. A pathophysiologic conceptual framework has been established to provide guidance. The goal of treatment should be pain reduction rather than complete pain relief. Surgical procedures have been used for specific causes of CP, but no one surgical technique helps relieve pain over the long term in all CP patients. Likewise, no one pharmacologic agent is successful in all CP patients, and pain relief is often incomplete. Pharmacologic treatment may take the form of stepwise addition of various agents, the cornerstone of which are antidepressants, followed by anticonvulsants, opioids, and other drugs. If all standard pharmacologic treatments fail, treatment of psychological problems induced by chronic pain is necessary since depression and the risk of suicide are significant in patients with poorly controlled CP.

Postherpes simplex type 1 neuralgia simulating postherpetic neuralgia.

Patients with prodromal neuralgia associated with recurrent herpes simplex type 1 (HST1) infection and chronic facial pain following years of relapsing HST1 have been described. Chronic neuralgia following a single clinical HST1 infection and simulating postherpetic neuralgia has not been previously reported. Such a case is described: A 49-yr-old woman with a 2-mo history of oral-facial dyskinesia developed burning pain and hypersensitivity of the left side of the tongue, lower gum, and inner cheek, followed 1 day later by a vesicular rash in the same painful distribution. Viral cultures of the lesions identified HST1 but not herpes zoster. Cerebrospinal fluid analyses during the vesicular lesion stage and 1 mo later were normal with no viral growth. Oral and facial lesions resolved after 10 days; acyclovir was given for 3 wk. Brain and brainstem magnetic resonance imaging (MRI), electroencephalogram, and brainstem evoked potential studies were normal. Hyperesthesias, allodynia, and burning pain persisted despite nonsteroidal antiinflammatory agents, codeine and hydrocodone. Oral opioids were administered until sedation occurred, with no relief of pain. The burning pain and hyperesthesia resolved after the 16th day of amitriptyline use, 75 mg/day. A trial off amitriptyline 6 mo later resulted in recurrence of pain, and amitriptyline was restarted with good pain control. Post-HST1 neuralgia may simulate postherpetic neuralgia clinically, and painful symptoms may respond to amitriptyline.

Central pain from cerebral abscess: thalamic syndrome in AIDS patients with toxoplasmosis.

We describe two patients with acquired immunodeficiency syndrome (AIDS) who developed classic thalamic syndrome (TS) due to Toxoplasma abscesses in the thalamic region. Treatment with amitriptyline provided substantial relief in both patients. Postmortem examination in one case revealed a lesion in the internal capsule and thalamic reticular nucleus. These observations indicate that (1) TS can result from an isolated lesion in the internal capsule and reticular nucleus of the thalamus, (2) cerebral abscess can cause classic TS, (3) central pain can be added to the many pain syndromes that afflict AIDS patients, and (4) an analgesic response to amitriptyline is possible in these patients.