Abstract/Text
BACKGROUND: Antiepileptic drugs have been used in pain management since the 1960s. Pregabalin is a recently developed antiepileptic drug also used in management of chronic neuropathic pain conditions.
OBJECTIVES: To assess analgesic efficacy and associated adverse events of pregabalin in acute and chronic pain.
SEARCH STRATEGY: We searched MEDLINE, EMBASE, and CENTRAL to May 2009 for randomised controlled trials (RCTs). Additional studies were identified from the reference lists of retrieved papers and on-line clinical trial databases.
SELECTION CRITERIA: Randomised, double blind trials reporting on the analgesic effect of pregabalin, with subjective pain assessment by the patient as either the primary or a secondary outcome.
DATA COLLECTION AND ANALYSIS: Two independent review authors extracted data and assessed trial quality. Numbers-needed-to-treat-to-benefit (NNTs) were calculated, where possible, from dichotomous data for effectiveness, adverse events and study withdrawals.
MAIN RESULTS: There was no clear evidence of beneficial effects of pregabalin in established acute postoperative pain. No studies evaluated pregabalin in chronic nociceptive pain, like arthritis.Pregabalin at doses of 300 mg, 450 mg, and 600 mg daily was effective in patients with postherpetic neuralgia, painful diabetic neuropathy, central neuropathic pain, and fibromyalgia (19 studies, 7003 participants). Pregabalin at 150 mg daily was generally ineffective. Efficacy was demonstrated for dichotomous outcomes equating to moderate or substantial pain relief, alongside lower rates for lack of efficacy discontinuations with increasing dose. The best (lowest) NNT for each condition for at least 50% pain relief over baseline (substantial benefit) for 600 mg pregabalin daily compared with placebo were 3.9 (95% confidence interval 3.1 to 5.1) for postherpetic neuralgia, 5.0 (4.0 to 6.6) for painful diabetic neuropathy, 5.6 (3.5 to 14) for central neuropathic pain, and 11 (7.1 to 21) for fibromyalgia.With 600 mg pregabalin daily somnolence typically occurred in 15% to 25% and dizziness occurred in 27% to 46%. Treatment was discontinued due to adverse events in 18 to 28%. The proportion of participants reporting at least one adverse event was not affected by dose, nor was the number with a serious adverse event, which was not more than with placebo.Higher rates of substantial benefit were found in postherpetic neuralgia and painful diabetic neuropathy than in central neuropathic pain and fibromyalgia. For moderate and substantial benefit on any outcome NNTs for the former were generally six and below for 300 mg and 600 mg daily; for fibromyalgia NNTs were much higher, and generally seven and above.
AUTHORS' CONCLUSIONS: Pregabalin has proven efficacy in neuropathic pain conditions and fibromyalgia. A minority of patients will have substantial benefit with pregabalin, and more will have moderate benefit. Many will have no or trivial benefit, or will discontinue because of adverse events. Individualisation of treatment is needed to maximise pain relief and minimise adverse events. There is no evidence to support the use of pregabalin in acute pain scenarios.
Abstract/Text
Since vasculitic neuropathy is treatable and potentially debilitating, clinicians should develop an approach to neuropathy that increases the likelihood of uncovering existing systemic or nonsystemic vasculitis. The presence of a connective tissue disease, systemic vasculitis, asymmetric or non--length-dependent axonal polyneuropathy, or multiple axonal mononeuropathies should heighten suspicion, but vasculitic neuropathy can also present as a distal symmetric polyneuropathy with or without other organ involvement. Electrodiagnostic testing utilizing extensive nerve conductions may be helpful in identifying features suggestive of vasculitic neuropathy and in selecting an abnormal nerve and muscle for biopsy confirmation. An array of laboratory tests may lead to identification of a systemic disorder that is either characterized by or predisposes to vasculitic neuropathy. The mainstays of treatment are corticosteroids and cyclophosphamide, but other drugs are used in specific conditions. With early diagnosis and careful monitoring of treatment regimens, the prognosis is usually good.
Abstract/Text
Vasculitis affecting the peripheral nerves predominantly manifests as subacute, progressive, asymmetric sensorimotor polyneuropathy or mononeuritis multiplex, and more rarely as painful mononeuropathy, pure sensory neuropathy, neuropathy of the cranial nerves, plexopathy, or as autonomic neuropathy. Vasculitic neuropathy may occur isolated or non-isolated (systemic) together with involvement of other organs. Systemic vasculitis with involvement of the peripheral nerves is further subdivided into primary (Takayasu syndrome, giant cell arteritis, classical panarteritis nodosa, thrombangitis obliterans, Kawasaki disease, Churg-Strauss syndrome, Wegener granulomatosis, cryoglobulinemic vasculitis, Behcet disease, microscopic polyangitis, Schoenlein Henoch purpura) or secondary systemic vasculitis (autoimmune connective tissue diseases, vasculitis from infection, sarcoidosis, malignancy, drugs, radiation, or diabetes). In addition to routine laboratory investigations and nerve conduction studies, nerve biopsy is essential for diagnosing the condition and to delineate it from differentials, although its sensitivity is only approximately 60%. Therapy of non-viral vasculitic neuropathy is based on corticosteroids and cyclophosphamide alone or in combination. Additional options include azathioprine, methotrexate, mycophenolate mofetil, or rituximab. In single cases immunoglobulins, immunoadsorbtion, or plasma exchange have been successfully applied. In case of virus-associated vasculitis interferon-alpha plus lamivudine or ribaverin may be beneficial.
Abstract/Text
Necrotizing vasculitis occurs as a primary phenomenon in connective tissue disorders and cognate fields, including polyarteritis nodosa and the Churg and Strauss syndrome variant, rheumatoid arthritis, systemic lupus and Wegener's granulomatosis. In all these conditions focal and multifocal neuropathy occur as a consequence of destruction of the arterial wall and occlusion of the lumen of small epineurial arteries. Vasculitis may also complicate the course of other conditions ranging from infection with the HIV and with the B and C hepatitis viruses to diabetes and sarcoidosis. Pathologically polymorphonuclear cells are present in the infiltrates of the vessel wall in primary necrotizing vasculitis, while in secondary vasculitis the inflammatory infiltrate is mainly composed of mononuclear cells. In all instances symptomatic vasculitis requires corticosteroid to control the inflammatory process and prevent further ischemic nerve lesions.
Abstract/Text
Sarcoidosis is a chronic disease of unknown aetiology. Neurosarcoidosis is registered in 5% of patients with sarcoidosis. Clinical manifestations of sarcoidosis are numerous and diverse. Manifestation of Neurosarcoidosis includes partial- and grand-mal seizures, low-grade fever, headache, increased intracranial pressure, visual disturbances, diabetes insipidus, amenorrhea- galacterorrhea syndrome and pituitary failure, hypogonadotropic hypogonadism, hyperprolactinemia, unilateral and bilateral facial palsy, infiltration of meninges (aseptic meningitis) and nerve roots, leptominingitis, pachymeningitis with cranial neuropathies, pseudotumor, mild cognitive disorder, psychosis, delirium, dementia, disorientation, amnesia, progressive visual deterioration and proptosis, axonal polyneuropathies, mononeuropathies, chronic polyradiculoneuritis, peripheral neuropathy, cranial nerve abnormalities, radiculopathies, peripheral neuropathy, mononeuritis multiplex, progressive numbness and deep sensation disturbance in bilateral lower extremities, hemiplegia, hyperreflexia with pathological reflexes and hypesthesia, upward gaze palsy, spinal cord compression, dysarthria, dysphagia, weakness, episodes of blurred vision, diplopia, intracerebral hemorrhage, neuro-ophthalmic manifestations, intranuclear ophthalmoplegia, dysorientation, vasculitis presenting with strokes, intracranial hypothalamic lesion, paresthesis, hemiparesis, myelopathy in the cervico-thoracic region, lumbar pain, sensory level and inability of lateral gaze (Tab. 2, Ref. 60).
Abstract/Text
Peripheral nerve dysfunction was a prominent clinical feature in each of three patients with the hypereosinophilic syndrome (HES). The neuropathy, occurring at the onset of marked eosinophilia or at a time of its worsening, had a painful onset, evolved over 1-4 weeks, and affected both sensory and motor function. Electrodiagnostic studies demonstrated both multifocal and generalized nerve involvement, with the former predominating (multiple mononeuropathy). Nerve and muscle biopsies from two patients revealed severe axonal degeneration with neurogenic atrophy of muscle. The eosinophilia decreased dramatically with corticosteroid treatment and the neuropathy gradually improved, but all three patients manifested residual neurologic disability 17-22 months after onset. The neuropathy may be on an ischemic basis or may be related to neurotoxicity of eosinophil products.
