Recommendations for the Management of Fibromyalgia

Transcription

1 2011 UBM Medica. Reprinted with permission from Medical Progress 2011 Vol. 38 No. 1. Pain management Recommendations for the Management of Fibromyalgia The Multidisciplinary Panel on Neuropathic Pain Chen Phoon Ping, MBBS, FHKAM (Anaes), FANZCA, FFPMANZCA, Dip Pain Mgt (HKCA); Josephine WY Ip, MBBS, MS, FRCS (Ed), FHKAM (Ortho), Dip Hand Surg (FESSH); Joseph MK Lam, MBChB, FRCS (Edin), FCSHK, FHKAM (Surg); Vincent Mok, MBBS, FHKAM (Med), FRCP (Edin), MD (CUHK); Tsoi Tak Hong, MBBS, MRCP, FRCP (Edin), FRCP (Lond), FRCP (Glas), FHKCP, FHKAM (Med); Wong Chun Por, MBBS, FHKAM (Med), FRCP (Lond), FRCP (Glas), FHKCP; Wong Ho Shan Steven, MBBS, FHKAM (Anaes), FANZCA, Dip Pain Mgt (HKCA) The main symptoms of fibromyalgia are chronic widespread musculoskeletal pain, fatigue, sleep disturbance, and cognitive impairment. Introduction: Epidemiology and Pathophysiology Fibromyalgia is characterized by widespread chronic musculoskeletal pain. 1 3 Most patients with fibromyalgia also experience fatigue, sleep disturbances and cognitive impairment, 3 and may also suffer from a range of other symptoms (Table 1) 4. Epidemiological studies estimate the prevalence of fibromyalgia to be between 2% and 4% in Western populations, 5,6 with the reported prevalence to be lower among Chinese populations in Hong Kong (0.82%) 7 and mainland China (0.05%). 5,8 Fibromyalgia is about 7 to 11 times more prevalent in women than in men, 4,6,9 with patients usually aged between 30 and 55 years at symptom onset. 3 Fibromyalgia has also been observed in men, children, adolescents, and the elderly. 10 Originally termed fibrositis, fibromyalgia was previously thought to be caused by inflammation of connective tissue of the muscle because of the presence of symptoms such as muscle pain and tenderness However, subsequent research has failed to reveal any evidence of inflammation as a possible cause of fibromyalgia. 12 While the exact aetiology of fibromyalgia is still unknown, current knowledge suggests that a disorder in central pain processing may play a role in its pathogenesis. 1 3 A number of mechanisms have been suggested in the pathogenesis of fibromyalgia, including central sensitization, abnormalities of descending inhibitory pain pathways, neurotransmitter abnormalities, and the presence of psychiatric comorbid conditions. 1 Elevated levels of substance P and nerve growth factor have been reported in some patients with fibromyalgia. 14 Evidence suggests that those with fibromyalgia experience pain differently from Medical Progress January

2 the general population. 1 Studies conducted by Buskila and colleagues on family members of diagnosed fibromyalgia patients revealed familial aggregation. 15,16 This finding suggests the involvement of both environmental and genetic factors in the aetiology of fibromyalgia. 17 A higher prevalence of fibromyalgia was observed in spouses of female patients, supporting the shared environmental aspects of its aetiology. 16 The children of female fibromyalgia patients were found to have a much higher incidence of fibromyalgia compared with the expected rate based on a polygenic multifactorial model for first-degree relatives. This suggests a polygenic mode of inheritance. 17 Genetic polymorphism affecting the serotoninergic, dopaminergic and catecholaminergic systems has also been demonstrated in fibromyalgia patients. 18,19 While non-specific to fibromyalgia, these polymorphisms have been found to occur at higher frequencies in fibromyalgia patients than in the general population. 17 These polymorphisms affect the metabolism and transport of monoamines and result in pathophysiological changes to both sensory processing and the stress response. 20 These genetic findings have been confirmed by functional magnetic resonance imaging studies, demonstrating the pathophysiological changes to pain processing that occur in fibromyalgia patients. 21,22 Other external stimuli may be associated with the onset or development of fibromyalgia. Several studies have reported that physical and psychological trauma, and acute infectious illness have occurred at or around the onset of fibromyalgia symptoms Although these external stimuli do not directly cause fibromyalgia, such trigger events (eg, post-traumatic stress disorder) have overlapping clinical Table 1. Common symptoms of fibromyalgia: concomitant with widespread chronic pain 4 Arthralgia Paraesthesia Morning stiffness Poor sleep Fatigue Irritable bowel symptoms Myalgia Headache Restless legs syndrome Cramps Concentration/Memory deficits Depression features that may contribute to the development of the syndrome. 17,26 Diagnosis The diagnosis of fibromyalgia is primarily based on clinical findings from a comprehensive review of patient history and a detailed physical examination. Patients suffering from fibromyalgia usually present with pain as the worst symptom; other key symptoms include fatigue, poor quality of sleep and cognitive impairment. 3 Diagnosis is further complicated, as patients might also present with a myriad of other clinical symptoms (Table 1) that are concomitant with other pain and rheumatic disorders. In the clinical setting, there is currently no laboratory test or study that can provide a conclusive or positive diagnosis for fibromyalgia. 3 Physicians are often presented with ambulatory patients who do not show all the symptoms associated with fibromyalgia. With many symptoms non-specific to fibromyalgia, differential diagnosis is necessary to exclude other rheumatic conditions with similar symptoms. Although it is important to exclude other conditions to effectively treat fibromyalgia, physicians should also avoid overinvestigation as patients may become frustrated having to undergo multiple inconclusive investigations. The classification criteria to standardize the definition of fibromyalgia Table 2. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia 1. History of widespread pain Pain must be present on the left and right sides of the body, and above and below the waist. In addition, axial skeletal pain must be present. Widespread pain must be present for at least 3 months. and 2. Pain in 11 of 18 tender point sites on digital palpation (approximate force of 4 kg) (see Figure 1) The sites are (bilaterally): occiput, low cervical, trapezius, supraspinatus, second rib, lateral epicondyle, gluteal, greater trochanter, and knee. For a tender point to be considered positive, the subject must state that the palpation was painful. Adapted from Wolfe F et al Medical Progress January 2011

3 Figure 1. Tender point sites for the American College of Rheumatology 1990 criteria for the classification of fibromyalgia Lower cervical Lateral epicondyle Knee were developed by the American College of Rheumatology (ACR) in Based on these criteria, a diagnosis of fibromyalgia can be made when the patient has a history of widespread pain for at least the past 3 months, and pain in 11 out of 18 tender point sites on digital palpation (Table 2; Figure 1). Widespread pain is considered to be present when the patient has pain in at least three quadrants of the body. Under these criteria, the diagnosis of fibromyalgia is not a diagnosis of exclusion and remains independent from other diagnoses. 25,27 Originally developed with the intention to facilitate the correlation of fibromyalgia studies from different research groups, the ACR 1990 classification criteria were not intended to be used for diagnosis in clinical practice. 20,25 The 11 tender point cut-off required by the ACR 1990 classification criteria has been the subject of some debate for its arbitrary nature because of the Occiput Second rib Trapezius Early identification and treatment of fibromyalgia may prevent the progression of its debilitating symptoms and limit its impact on the patient s quality of life. Generally, a multidisciplinary approach combining both pharmacological and non-pharmacological intervention should be used in the management of fibromyalgia for optimal treatment outcomes. 10,30,31 The goal of any treatment regimen should focus on relieving pain and improving daily function. Patients should commence treatment once the major symptoms of fibromyalgia are present, even if they do not necessarily fulfil the ACR 1990 or 2010 criteria. Physicians should first determine the predominant underlying factor whether the patient s symptoms are primarily of psychological or muscu- Supraspinatus Gluteus Greater trochanter lack of a clear association between tender point pain and the underlying pathophysiology in fibromyalgia. 20,25,28 Furthermore, the tender point count is rarely performed in routine clinical practice. 29 The criteria also did not consider the importance of coexisting symptoms of fibromyalgia. 29 The ACR has recently published the diagnostic criteria for fibromyalgia. 29 The ACR 2010 diagnostic criteria, as summarized in Table 3, were designed to be simple and practical for use in primary and specialty practice without requiring a tender point examination and to provide a severity scale for characteristic fibromyalgia symptoms; this definition of fibromyalgia has correctly classified 88.1% of the cases classified by the ACR 1990 criteria. While the ACR 2010 criteria have eliminated the need for a tender point examination, all patients should continue to have a physical examination that may include examination of tender point sites. The ACR 2010 criteria also require that patients have had a similar level of symptoms for at least 3 months, similar to the requirement for widespread pain for at least 3 months in the ACR 1990 criteria. The authors have indicated that the ACR 2010 diagnostic criteria are not meant to replace the ACR 1990 classification criteria, but can be an alternative method of diagnosis. Furthermore, the ACR 2010 symptom severity scale can provide a baseline for longer-term evaluation to monitor a patient s progress. Physicians should begin early treatment for patients with pre-fibromyalgia, ie, those who present with the major symptoms of fibromyalgia but may be just outside the ACR 1990 classification or ACR 2010 diagnostic criteria. Patients should be referred for specialist treatment if their symptoms are refractory to treatment and/or meet the ACR 1990 classification criteria for fibromyalgia. Management of Fibromyalgia Medical Progress January

4 loskeletal origin before providing the appropriate treatment. Pharmacological therapies should be selected according to the symptoms experienced by individual patients (Figure 2). In addition, non-pharmacological therapies, such as physical therapy, lifestyle changes and cognitive behavioural therapy (CBT), and interventions, such as acupuncture and trigger point injection, should be considered to complement any pharmacological treatments and to improve the overall well-being of the patient. During treatment, patients should be educated to understand that medications may take several weeks to reach full efficacy and a trial process may be required to ascertain a suitable drug to relieve fibromyalgia symptoms. As the immediate effect of the drug on fibromyalgia may diminish in the longer term (> 13 weeks), physicians should be aware of the need to use different drugs in rotation to relieve pain. 2 Furthermore, as fibromyalgia patients are unusually sensitive to adverse effects of medication, treatment should be started at a low dose and be slowly titrated to minimize potential side effects. 3 Evidence-based Management of Fibromyalgia Pharmacological Management Options There is limited published evidence for drug efficacy in fibromyalgia; however, the drugs outlined in these recommendations are effective in a variety of neuropathic pain syndromes. Where appropriate, trials in fibromyalgia patients will be described below; however, some of the evidence is derived from patients with other neuropathies. Some agents are not licensed for use in neuropathic pain. Full prescribing information should be consulted before initiating therapy. Figure 2. Change in pain score from baseline in patients treated with pregabalin or placebo 7 Pharmacological therapy α 2 -δ Ligands (eg, pregabalin, gabapentin) Tricyclic antidepressants (eg, amitriptyline) SNRIs (eg, duloxetine, milnacipran) Weak opioids and/or analgesics (tramadol or/and acetaminophen) Diagnosis ACR 1990 ACR 2010 Multidisciplinary approach a α 2 -δ Ligands α 2 -δ Ligands act directly on the central nervous system by binding to the α 2 -δ subunit of voltage-gated calcium channels to disrupt neuronal signalling. Pregabalin is the first medication to receive US Food and Drug Agency (FDA) approval for treatment of fibromyalgia and is currently the only drug in Hong Kong to be indicated for fibromyalgia monotherapy. It can be considered as an option for first-line treatment of fibromyalgia. 32 Pregabalin has been studied in randomized, double-blind, placebocontrolled trials as monotherapy for fibromyalgia The safety and efficacy of pregabalin were evaluated in an 8-week trial, during which patients received either placebo or pregabalin (150, 300 or 450 mg/day). 33 Patients receiving pregabalin at 450 mg/day achieved significant pain reduction over the placebo group (-0.93 on a 0 10 scale; P < 0.001), and significantly more Non-pharmacological therapy Physical therapy (exercise, physiotherapy, occupational therapy, aquatherapy/hydrotherapy) Lifestyle changes (improve sleep hygiene, healthy diet, relaxation techniques) Cognitive behavioural therapy Acupuncture Trigger point injection CR = American College of Rheumatology; SNRI = serotonin-norepinephrine reuptake inhibitors. CR = American College of Rheumatology; SNRI = serotonin-norepinephrine reuptake inhibitors. a Refer to specialist/pain clinic if the patient meets the ACR 1990/2010 criteria and/or if refractory to treatment. patients achieved 50% improvement in pain at endpoint (29% vs 13% in the placebo group; P = 0.003). Patients receiving 300 and 450 mg/day also achieved significant improvements in sleep quality and reduction of fatigue. 33 In two other trials in which patients received placebo or pregabalin (300, 450 or 600 mg/day) for 13 and 14 weeks, 34,35 there were significant improvements in endpoint mean pain score, patient global impression of change (PGIC), and assessment of sleep. The benefit of pregabalin was evident 1 week after onset of treatment. Improvements in the PGIC scores were significant for all pregabalin groups, and the fibromyalgia impact questionnaire (FIQ) total scores were numerically greater for both trials but only statistically significantly for one trial. 34 The most commonly reported adverse events were dizziness and somnolence. 34,35 The fibromyalgia relapse evaluation 8 Medical Progress January 2011

5 Table 3. The American College of Rheumatology 2010 diagnostic criteria for fibromyalgia Criteria A patient satisfies the diagnostic criteria for fibromyalgia if the following three conditions are met: 1. Widespread pain index (WPI) 7 and symptom severity (SS) scale score 5 or WPI 3 6 and SS scale score 9 2. Symptoms have been present at a similar level for at least 3 months 3. The patient does not have a disorder that would otherwise explain the pain Ascertainment 1. WPI Note the number of areas in which the patient has had pain over the last week. In how many areas has the patient had pain? The score will be between 0 and 19. Shoulder girdle, left Hip (buttock, trochanter), left Jaw, left Upper back Shoulder girdle, right Hip (buttock, trochanter), right Jaw, right Lower back Upper arm, left Upper leg, left Chest Neck Upper arm, right Upper leg, right Abdomen Lower arm, left Lower leg, left Lower arm, right Lower leg, right 2. SS scale score Fatigue Waking unrefreshed Cognitive symptoms For each of the three symptoms above, indicate the level of severity over the past week using the following scale: 0 = no problem 1 = slight or mild problems, generally mild or intermittent 2 = moderate, considerable problems, often present and/or at a moderate level 3 = severe: pervasive, continuous, life-disturbing problems Considering somatic symptoms in general, indicate whether the patient has: 0 = no symptoms 1 = few symptoms 2 = a moderate number of symptoms 3 = a great deal of symptoms The SS scale score is the sum of the severity of the three symptoms plus the extent (severity) of somatic symptoms in general. The final score is between 0 and 12. Adapted from Wolfe F et al. 29 and efficacy for durability of meaningful relief (FREEDOM) study was a 6-month, randomized, double-blind, placebo-controlled, discontinuation trial designed to evaluate the efficacy of pregabalin monotherapy for durability of effect on fibromyalgia pain. 36 Patients who responded to an initial 6-week open-label treatment period with pregabalin ( 50% decrease in pain visual analogue scale and at least much improved on PGIC) were eligible to enter the double-blind phase. Optimal doses of pregabalin were determined during the first 3 weeks by escalation of doses, and patients continued to receive their determined optimal doses for the subsequent 3 weeks of openlabel treatment (300, 450 or 600 mg/ day). Patients were then randomized to receive placebo or pregabalin over an additional 26 weeks to determine the durability of effects for relieving fibromyalgia pain. Time to loss of therapeutic response (< 30% reduction in pain from open-label baseline or worsening of fibromyalgia symptoms) was significantly longer for pregabalintreated patients than those on placebo (P < ), demonstrating durability of benefit in longer-term treatment. The efficacy and safety of pregabalin in fibromyalgia treatment was confirmed by an independent metaanalysis of five separate randomized, double-blind, placebo-controlled trials. 37 Gabapentin is an α 2 -δ ligand that is structurally related to pregabalin. In a 12-week randomized, double-blind trial in which patients received placebo or gabapentin (1,200 or 2,400 mg/ day), gabapentin significantly improved pain scores, with more achieving response at endpoint (defined as > 30% improvement in pain severity; 51% vs 31%, P = 0.014), as well as sleep quality and FIQ scores. 38 Common side effects similar to those of pregabalin, including dizziness, sedation and weight gain, were reported; most were mild to moderate in severity. 38 Serotonin norepinephrine Reuptake Inhibitors The serotonin norepinephrine reuptake inhibitors (SNRIs), duloxetine and milnacipran, are newer options for fibromyalgia treatment. They are the second and third drugs, respectively, to be approved by the FDA for the treatment of fibromyalgia. The efficacy and safety of duloxetine has been studied in four randomized placebo-controlled trials of 3 or 6 months duration, and two 6-month extension trials. These studies demonstrated that duloxetine at 60 or 120 mg/day significantly improved pain Medical Progress January

6 severity and patient global impression of improvement scores, as well as other secondary clinical outcomes including FIQ, clinical global impression of severity, fatigue, and quality of life. Common side effects included insomnia, dry mouth, constipation, and increase in heart rate. 39 Pooled analysis of data from five clinical trials further confirmed the safety and efficacy of duloxetine in the treatment of fibromyalgia. 40 Milnacipran has also been investigated in four randomized placebo-controlled trials at a dose of mg/day. It has been shown to significantly improve pain scores and increase the proportion of responders compared with placebo. 39 The side effects experienced by the patients were similar to those reported with duloxetine. 2 Meta-analysis of FDA-approved Medications A recently published meta-analysis compared the efficacy and harms of pregabalin, duloxetine and milnacipran in fibromyalgia. 41 While no head-to-head studies were available, indirect comparisons via a common comparator were possible; 11 placebocontrolled trials with a total of 6,388 patients enrolled were included in the meta-analysis. All drugs demonstrated greater symptom control than placebo did, except for duloxetine for fatigue, milnacipran for sleep disturbance, and pregabalin for depressed mood. Significant differences in average symptom reduction were shown: duloxetine and pregabalin were superior to milnacipran in reducing pain and sleep disturbances; duloxetine was superior to milnacipran and pregabalin in reducing depressed mood; and milnacipran and pregabalin were superior to duloxetine in reducing fatigue. Furthermore, the risk of headache and nausea with pregabalin was lower than with duloxetine and milnacipran, and the risk of diarrhoea was higher with duloxetine than with the other agents. The analysis found no significant differences between 30% pain relief and dropout rates due to adverse events among the three drugs. Numbers needed to treat (NNTs) for 30% pain relief were 8.6 for pregabalin, 7.2 for duloxetine and 19 for milnacipran. The NNTs for dropout due to lack of efficacy were -16.0, and for pregabalin, duloxetine and milnacipran, respectively. Numbers needed to harm for dropout due to side effects were 7.6 for pregabalin, 14.9 for duloxetine and 7.6 for milnacipran. The authors concluded that there is evidence for short-term (up to 6 months) efficacy for the three drugs. Moreover, when considering a drug to treat fibromyalgia, consideration should be given to the patients key symptoms. Drug therapy should be initiated at a low dose and titrated slowly, if required, with effects re-evaluated at regular intervals. Tricyclic Antidepressants Tricyclic antidepressants (TCAs) are not approved by the FDA for the treatment of fibromyalgia. However, TCAs, particularly amitriptyline and cyclobenzaprine (which is classified as a centrally acting skeletal muscle relaxant), have been demonstrated to provide some short-term benefit (up to 12 weeks) to patients with fibromyalgia and are recommended treatment options. 2,31 While TCAs have been traditionally considered as the first-line treatment for fibromyalgia, 38 their efficacy is limited by poor tolerability, with up to 85% of patients experiencing side effects, and loss of therapeutic response in longerterm treatment (between 12 and 26 weeks). 2 Other Agents Tramadol is a synthetic opioid analgesic which binds to the µ-opioid receptor. The safety and efficacy of tramadol in treating fibromyalgia was evaluated in three controlled studies, both with and without acetaminophen. 2,42 Patients using tramadol alone responded positively to treatment and experienced a reduction in pain. The dropout rate, predominantly from inadequate pain relief, was also significantly lower with tramadol than with placebo. 42 Tramadol in combination with acetaminophen was also able to achieve pain outcomes similar to the use of tramadol alone. However, this combination therapy was able to achieve significantly lower dropout rates, and patients recorded significant improvement in pain and improved physical functions. 42 Tramadol is recommended as a treatment for fibromyalgia by the European League Against Rheumatism 31 and the American Pain Society. 30 Non-pharmacological Management Options A multidisciplinary approach to managing the symptoms of fibromyalgia, including non-pharmacological treatments to complement pharmacotherapy, is necessary. A recent report found that following a 3-month outpatient programme integrating physiotherapy, occupational therapy, nursing and CBT, longer-term improvement in disability was influenced by selfefficacy and general adherence during treatment. 43 A number of non-pharmacological treatment options are available, and should be tailored to an individual s symptoms and preferences. Physical Therapy Physical therapy such as exercise, phys- 10 Medical Progress January 2011

7 iotherapy or occupational therapy should aim to help patients maintain their daily function. 42 Although there are conflicting opinions on the efficacy of exercise in the management of fibromyalgia, there is moderate evidence to suggest that aerobic exercise and strength training improve overall fitness and pain thresholds. Exercise programmes should be tailored individually and intensity of exercise should be increased gradually so as not to worsen the patient s symptoms. In addition, aquatherapy or hydrotherapy in a heated pool is well tolerated and beneficial in relieving pain. 2,30,31 Lifestyle Changes Changes to the patient s lifestyle, such as improving sleep hygiene to maximize sleep, having a balanced and healthy diet, practicing meditation or relaxation techniques and patient education on fibromyalgia, may be beneficial. 3 Cognitive Behavioural Therapy Cognitive behavioural therapy has been shown to be effective in reducing pain and improving function in randomized controlled trials. The major aim of CBT is to help patients understand how emotions and cognitive factors (thoughts, memories, beliefs, expectations, fears) affect the way the patient handles sensory inputs. 3,30,31,42 In a recent systematic review and metaanalysis, CBT was reported to improve self-efficacy and coping with pain, and to reduce depressed mood and health care-seeking behaviour. 44 Acupuncture Acupuncture has yielded conflicting results when used to treat fibromyalgia patients. This can be attributed to studies not being adequately blinded. An electroacupuncture trial showed an improvement in FIQ score compared with sham acupuncture study, while another study did not demonstrate any significant improvement between traditional and sham acupuncture. A meta-analysis of controlled clinical trials on acupuncture concluded that acupuncture has a small but insignificant analgesic effect for fibromyalgia and is not recommended as monotherapy for managing fibromyalgia. 45 Trigger Point Injection Trigger point injection has been shown to be an effective procedure for pain relief, although there is no data currently available to demonstrate the long-term effects. One study showed that fibromyalgia patients with myofascial pain syndrome had significant improvement in subjective pain intensity, pain threshold, and range of movement 2 weeks after trigger point injection. 46 Summary Fibromyalgia is a non-inflammatory pain disorder of unknown aetiology. It occurs predominantly in women aged between 30 and 55 years at symptom onset. The main symptoms are chronic widespread pain, fatigue, sleep disturbance, and cognitive impairment. While no laboratory test or study is able to provide a positive diagnosis for fibromyalgia, physicians should begin treatment for patients when they present with the key symptoms. A multidisciplinary approach combining both pharmacological and non-pharmacological treatments should be used in the management of fibromyalgia, with the goals of relieving pain and improving daily function. A tailored treatment approach is necessary, with treatment individualized to a patient s symptoms. Pregabalin, duloxetine and milnacipran are currently the only medications approved by the FDA for the treatment of fibromyalgia. However, other agents, such as gabapentin, TCAs and tramadol, have been demonstrated to provide beneficial effects to patients. Non-pharmacological options, such as physical therapy, lifestyle changes and CBT, and interventions, such as acupuncture and trigger point injection, have also been shown to benefit some fibromyalgia patients, and should be considered as complementary therapy in a patient s individualized treatment programme. Declaration of Interests The Multidisciplinary Panel on Neuropathic Pain is supported by an unrestricted educational grant from Pfizer Corporation Hong Kong Ltd. A list of references can be obtained from the editor upon request. About the Authors Dr Chen is Consultant and Chief of Service, Department of Anaesthesiology and Operating Services, Alice Ho Miu Ling Nethersole Hospital and North District Hospital, and Adjunct Associate Professor, The Chinese University of Hong Kong, Hong Kong SAR. Dr Ip is Associate Professor and Chief, Division of Hand and Foot Surgery, Department of Orthopaedic Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR. Dr Lam is Honorary Consultant and Honorary Clinical Associate Professor, Division of Neurosurgery, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR. Dr Mok is Associate Professor and Honorary Associate Consultant, Division of Neurology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR. Dr Tsoi is Neurologist and Consultant Physician, Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Hong Kong SAR. Dr CP Wong is Chief, Integrated Medical Services, and Consultant and Head, Department of Geriatrics, Ruttonjee and Tang Shiu Kin Hospitals, Hong Kong SAR. Dr S Wong is Consultant Anaesthesiologist and Head of the Pain Management Team, Department of Anaesthesiology and Operating Theatre Services, Queen Elizabeth Hospital, Hong Kong SAR. Medical Progress January