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Abdel-Aziz and Ghaleb Sincerely yours, ANA OLIVEIRA, MSc,*†‡ RICARDO JORGE DINIS-OLIVEIRA, PhD,*‡§¶ AUGUSTO NOGUEIRA, MSc,† ANDREIA S. AZEVEDO, MSc,† FERRAZ GONÇALVES, PhD,** PAULA SILVA, MD,** FÉLIX CARVALHO, PhD,* and RUI MEDEIROS, PhD†,††‡‡§§ *Department of Biological Sciences, Faculty of Pharmacy; §Department of Legal Medicine and Forensic Sciences, Faculty of Medicine, University of Porto, Porto; †Molecular Oncology GRP and VirologyLB, Portuguese Institute of Oncology-Porto, Porto; ‡ Department of Sciences, Advanced Institute of Health Sciences—North, CESPU, CRL, Gandra; ¶Department of Diagnostic and Therapeutic Technologies, Polytechnic Health Institute—North, CESPU, CRL, Vila Nova de Famalicão; **Palliative Care Unit, Portuguese Institute of Oncology -Porto, Porto; ††ICBAS, Abel Salazar Institute for the Biomedical Sciences, Porto; ‡‡CEBIMED, Faculty of Health Sciences of Fernando Pessoa University, Porto; §§LPCC, Liga Portuguesa Contra o Cancro, Núcleo Regional do Norte, Porto, Portugal
References 1 Muralidharan A, Smith MT. Pain, analgesia and genetics. J Pharm Pharmacol 2011;63:1387–400. 2 Meng QC, Soleded Cepeda M, Kramer T, et al. Highperformance liquid chromatographic determination of morphine and its 3- and 6-glucuronide metabolites by two-step solid-phase extraction. J Chromatogr B Biomed Sci Appl 2000;742:115–23.
3 Sia AT, Lim Y, Lim ECP, et al. A118G single nucleotide polymorphism of human mu-opioid receptor gene influences pain perception and patient-controlled intravenous morphine consumption after intrathecal morphine for postcesarean analgesia. Anesthesiology 2008;109: 520–6. 4 Zubieta J-K, Heitzeg MM, Smith YR, et al. COMT val158met genotype affects μ-opioid neurotransmitter responses to a pain stressor. Science 2003;299: 1240–3. 5 Jensen KB, Lonsdorf TB, Schalling M, Kosek E, Ingvar M. Increased sensitivity to thermal pain following a single opiate dose is influenced by the COMT Val158Met polymorphism. PLoS ONE 2009;4:e6016. 6 Loggia ML, Jensen K, Gollub RL, et al. The catecholO-methyltransferase (COMT) val158met polymorphism affects brain responses to repeated painful stimuli. PLoS ONE 2011;6:e27764. 7 Holthe M, Klepstad P, Zahlsen K, et al. Morphine glucuronide-to-morphine plasma ratios are unaffected by the UGT2B7 H268Y and UGT1A1*28 polymorphisms in cancer patients on chronic morphine therapy. Eur J Clin Pharmacol 2002;58:353–6. 8 Parmar S, Stingl JC, Huber-Wechselberger A, et al. Impact of UGT2B7 His268Tyr polymorphism on the outcome of adjuvant epirubicin treatment in breast cancer. Breast Cancer Res 2011;13:R57. 9 Christrup LL. Morphine metabolites. Acta Anaesthesiol Scand 1997;41:116–22.
Cervical Spinal Cord Stimulation for the Management of Pain from Brachial Plexus Avulsion Dear Editor, Almost 80% of patients with brachial plexus avulsion develop chronic pain. The pain can be treated medically or with more invasive surgical procedures. However, in most cases, the pain is resistant to medical treatment and has a high-recurrence rate after invasive procedures like dorsal root entry zone (DREZ) lesioning. Cervical spinal cord stimulation (SCS) is one of the underutilized treatment modalities with several reports of good outcome. We report a case of significant improvement in pain from brachial plexus avulsion injury after implanting a cervical SCS. A 25-year-old male patient was involved in a motor vehicle accident 5 years ago. He suffered from multiple injuries including injury to his right brachial plexus. 712
Magnetic resonance imaging (MRI) showed complete nerve root avulsion from C6 to T1. He lost sensation and motor function below the deltoid in his right upper extremity, however his main debilitating problem was severe chronic pain. He described his pain as burning, stabbing, and sometime like an electric shock, starting at the shoulder and radiating to the arm and his five fingers, with an intensity of 7/10 on a numeric pain rating scale. On examination, he had no sensation or motor function below the deltoid. He was not interested in functional recovery and was only concerned about relieving the pain. Medical management with a combination of an antidepressant, an anticonvulsant, a nonsteroidal antiinflammatory medication, and an opioid failed to improve his pain. Decision was made to proceed with a cervical spinal cord stimulator trial.
Letters to the Editor We entered the epidural space at C7-T1 level using a paramedian approach. Under fluoroscopy guidance, we advanced the lead until the tip was seen at the C3 level. The electrodes were covering the area from C3 to C6 (Figure 1). With stimulation the patient reported a decrease in his pain level with complete coverage of his right upper extremity and right shoulder. We fixed the stimulator in place and asked the patient to monitor the efficacy of the stimulator on decreasing his pain level and improving his quality of life and to return to the clinic in 3 days. On his follow-up visit, the patient reported a 50% reduction in pain intensity and was satisfied with the result. Decision was made to proceed with implantation of a permanent stimulator. An SCS with paddle-type leads was placed by a neurosurgeon covering the area from C3 to C5 (Figure 2). On 1-month follow-up, the patient continued to report a good coverage of his pain with no recurrence. Most brachial plexus avulsion injuries are traumatic in origin, mainly caused by motor vehicle accidents or industrial injuries. One of the most serious and disabling consequences of brachial plexus avulsion is chronic pain with an incidence of 80% [1]. Most patients describe the pain as a burning sensation, or similar to pins and needles, or an electric shock. In addition to the constant pain, patients typically complain of periodic sharp paroxysms of pain lasting several seconds [2]. The pain usually begins within days of injury and generally persists [2,3]. The origin of the pain has been attributed to root avulsion and spinal cord deafferentation. It is thought that the lack of sensory input into the spinal cord leads to spontaneous activity of the neurons in the dorsal horn, thereby causing pain [2].
Figure 2 Permanent paddle cervical spinal cord stimulation. This pain is unfortunately very resistant to many forms of therapy. Patients are initially treated medically with a combination of anticonvulsants, antidepressants, nonsteroidal anti-inflammatory drugs, or opioids. Surgical procedures for repair of brachial plexus lesions, like repair with autologous grafts, extraplexual or intraplexual nerve transfers, are reported to help in relieving the pain in some cases [4]. If pain persists despite medical management or surgical repair, other invasive treatment modalities like DREZ lesioning and cervical SCS are indicated. For many, DREZ lesioning is the preferred procedure for treating intractable pain due to brachial plexus avulsion. Several studies show that DREZ lesioning produces excellent pain relief in the early postoperative period with 75% to 98.2% of patients having good results immediately after surgery [5,6]. However, the rate of pain recurrence is very high in long-term follow-up [5,6], with many patients undergoing more DREZ lesioning procedures or alternative treatment modalities like SCS.
Figure 1 Cervical spinal cord stimulation trial.
SCS has been used successfully in the treatment of chronic neuropathic pain conditions like failed back surgery syndrome, complex regional pain syndrome, peripheral nerve lesions, and phantom limb pain. Many articles reported the use of SCS for treatment of pain caused by brachial plexus avulsion. Bennet et al. reported five cases of pain caused by brachial plexus avulsion treated with dorsal column stimulation, where all five patients achieved good or excellent pain relief during 13.5 months of follow-up [7]. Piva et al. reported four cases treated with cervical SCS where all attained significant pain relief [8]. Brill et al. reported two cases 713
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López-Mesonero et al. treated with cervical SCS that achieved significant pain reduction and significant reduction of analgesic drug consumption [9]. Lai et al. reported a case of successful pain reduction with high-cervical SCS in a patient who underwent two failed DREZ lesioning procedures [10]. While Bennet et al., Piva et al., and Brill et al. used SCS without a previous DREZ lesioning, Lai et al. prefer DREZ as the first line of treatment after failure of medical management, as it has lower cost than SCS and good immediate outcome. However, with DREZ lesioning, inaccurate lesions can cause complications such as lower extremity weakness, loss of bowel or bladder function, or sexual dysfunction [5,6], as well as a reported high-recurrence rate [5,6]. Our patient reported a significant reduction in pain, 50% improvement, with placement of the trial stimulator at C3–C6 level and continued to have the same coverage and same reduction in pain level after the surgical placement of the paddle stimulator at C3–C5 level. We placed the stimulator above the level of root avulsion as it appears that spinal cord stimulation primarily affects the dorsal column, the spinothalamic tract and the descending pain inhibitory pathway, Lai et al. also reported a good outcome with placement of high-cervical SCS [10]. In conclusion, cervical SCS can be an effective treatment modality for patients with neuropathic pain from brachial plexus avulsion. We recommend an SCS trial in patients with pain resistant to medical management or those with persisting pain despite surgical repair or DREZ lesioning. We recommend placing the stimulator above the avulsion level. More studies on larger patient populations with longterm follow-up and comparison with other treatment modalities are needed to establish guidelines for the treatment of this group of patients who suffer from a debilitating problem that affects their quality of life and their productivity.
SAMER ABDEL-AZIZ, MD, and AHMED H. GHALEB, MD Department of Anesthesiology and Pain Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
References 1 Bertelli JA, Ghizoni MF. Use of clinical signs and computed tomography myelography findings in detecting and excluding nerve root avulsion in complete brachial plexus palsy. J Neurosurg 2006;105:835–42. 2 Parry CB. Pain in avulsion lesions of the brachial plexus. Pain 1980;9:41–53. 3 Narakas AO. Pain syndromes in brachial plexus injuries. In: Brunelli G, ed. Textbook of Microsurgery. Milan: Masson; 1988:809–16. 4 Bonilla G, Di Masi G, Battaglia D, Otero J, Socolovsky M. Pain and brachial plexus lesions: Evaluation of initial outcomes after reconstructive microsurgery and validation of a new pain severity scale. Acta Neurochir 2011;153:171–6. 5 Samii M, Bear-Henney S, Ludemann W, Tatagiba M, Blomer U. Treatment of refractory pain after brachial plexus avulsion with dorsal root entry zone lesions. Neurosurgery 2001;48:1269–77. 6 Sindou MP. Microsurgical lesioning in the dorsal root entry zone for pain due to brachial plexus avulsion: A prospective series of 55 patients. J Neurosurg 2005;102:1018–28. 7 Bennet MI, Tai YM. Cervical dorsal column stimulation relieves pain of brachial plexus avulsion. J R Soc Med 1994;87:5–6. 8 Piva B, Shaladi A, Saltari R, Gilli G. Spinal cord stimulation in the management of pain from brachial plexus avulsion. Neuromodulation 2003;6:27–31. 9 Brill S, Aryeh I. Neuromodulation in the management of pain from brachial plexus injury. Pain Physician 2008;11:81–5. 10 Lai HY, Lee CY, Lee ST. High cervical spinal cord stimulation after failed dorsal root entry zone surgery for brachial plexus avulsion pain. Surg Neurol 2009;72(3):286–9.
Nummular Headache in a Patient with Craniosynostosis: One More Evidence for a Peripheral Mechanism Dear Editor, Nummular headache (NH) is a normally mild-to-moderate pain felt in a coin-shaped or elliptical area of the head, typically 1 to 6 cm in diameter. The affected area may show several combinations of sensory signs, such as hypoesthesia, paresthesia, dysesthesia, and tenderness 714
[1,2]. In addition, a few patients develop local alopecia or other trophic changes [3]. NH was described in 2002 [1], and has already been reported in 238 cases according to a recent review [4]. Although NH emerged as a primary disorder, we have to pay attention to possible symptomatic or secondary cases. Here we report a case of NH associated with craniosynostosis.
Abdel-Aziz and Ghaleb Sincerely yours, ANA OLIVEIRA, MSc,*†‡ RICARDO JORGE DINIS-OLIVEIRA, PhD,*‡§¶ AUGUSTO NOGUEIRA, MSc,† ANDREIA S. AZEVEDO, MSc,† FERRAZ GONÇALVES, PhD,** PAULA SILVA, MD,** FÉLIX CARVALHO, PhD,* and RUI MEDEIROS, PhD†,††‡‡§§ *Department of Biological Sciences, Faculty of Pharmacy; §Department of Legal Medicine and Forensic Sciences, Faculty of Medicine, University of Porto, Porto; †Molecular Oncology GRP and VirologyLB, Portuguese Institute of Oncology-Porto, Porto; ‡ Department of Sciences, Advanced Institute of Health Sciences—North, CESPU, CRL, Gandra; ¶Department of Diagnostic and Therapeutic Technologies, Polytechnic Health Institute—North, CESPU, CRL, Vila Nova de Famalicão; **Palliative Care Unit, Portuguese Institute of Oncology -Porto, Porto; ††ICBAS, Abel Salazar Institute for the Biomedical Sciences, Porto; ‡‡CEBIMED, Faculty of Health Sciences of Fernando Pessoa University, Porto; §§LPCC, Liga Portuguesa Contra o Cancro, Núcleo Regional do Norte, Porto, Portugal
References 1 Muralidharan A, Smith MT. Pain, analgesia and genetics. J Pharm Pharmacol 2011;63:1387–400. 2 Meng QC, Soleded Cepeda M, Kramer T, et al. Highperformance liquid chromatographic determination of morphine and its 3- and 6-glucuronide metabolites by two-step solid-phase extraction. J Chromatogr B Biomed Sci Appl 2000;742:115–23.
3 Sia AT, Lim Y, Lim ECP, et al. A118G single nucleotide polymorphism of human mu-opioid receptor gene influences pain perception and patient-controlled intravenous morphine consumption after intrathecal morphine for postcesarean analgesia. Anesthesiology 2008;109: 520–6. 4 Zubieta J-K, Heitzeg MM, Smith YR, et al. COMT val158met genotype affects μ-opioid neurotransmitter responses to a pain stressor. Science 2003;299: 1240–3. 5 Jensen KB, Lonsdorf TB, Schalling M, Kosek E, Ingvar M. Increased sensitivity to thermal pain following a single opiate dose is influenced by the COMT Val158Met polymorphism. PLoS ONE 2009;4:e6016. 6 Loggia ML, Jensen K, Gollub RL, et al. The catecholO-methyltransferase (COMT) val158met polymorphism affects brain responses to repeated painful stimuli. PLoS ONE 2011;6:e27764. 7 Holthe M, Klepstad P, Zahlsen K, et al. Morphine glucuronide-to-morphine plasma ratios are unaffected by the UGT2B7 H268Y and UGT1A1*28 polymorphisms in cancer patients on chronic morphine therapy. Eur J Clin Pharmacol 2002;58:353–6. 8 Parmar S, Stingl JC, Huber-Wechselberger A, et al. Impact of UGT2B7 His268Tyr polymorphism on the outcome of adjuvant epirubicin treatment in breast cancer. Breast Cancer Res 2011;13:R57. 9 Christrup LL. Morphine metabolites. Acta Anaesthesiol Scand 1997;41:116–22.
Cervical Spinal Cord Stimulation for the Management of Pain from Brachial Plexus Avulsion Dear Editor, Almost 80% of patients with brachial plexus avulsion develop chronic pain. The pain can be treated medically or with more invasive surgical procedures. However, in most cases, the pain is resistant to medical treatment and has a high-recurrence rate after invasive procedures like dorsal root entry zone (DREZ) lesioning. Cervical spinal cord stimulation (SCS) is one of the underutilized treatment modalities with several reports of good outcome. We report a case of significant improvement in pain from brachial plexus avulsion injury after implanting a cervical SCS. A 25-year-old male patient was involved in a motor vehicle accident 5 years ago. He suffered from multiple injuries including injury to his right brachial plexus. 712
Magnetic resonance imaging (MRI) showed complete nerve root avulsion from C6 to T1. He lost sensation and motor function below the deltoid in his right upper extremity, however his main debilitating problem was severe chronic pain. He described his pain as burning, stabbing, and sometime like an electric shock, starting at the shoulder and radiating to the arm and his five fingers, with an intensity of 7/10 on a numeric pain rating scale. On examination, he had no sensation or motor function below the deltoid. He was not interested in functional recovery and was only concerned about relieving the pain. Medical management with a combination of an antidepressant, an anticonvulsant, a nonsteroidal antiinflammatory medication, and an opioid failed to improve his pain. Decision was made to proceed with a cervical spinal cord stimulator trial.
Letters to the Editor We entered the epidural space at C7-T1 level using a paramedian approach. Under fluoroscopy guidance, we advanced the lead until the tip was seen at the C3 level. The electrodes were covering the area from C3 to C6 (Figure 1). With stimulation the patient reported a decrease in his pain level with complete coverage of his right upper extremity and right shoulder. We fixed the stimulator in place and asked the patient to monitor the efficacy of the stimulator on decreasing his pain level and improving his quality of life and to return to the clinic in 3 days. On his follow-up visit, the patient reported a 50% reduction in pain intensity and was satisfied with the result. Decision was made to proceed with implantation of a permanent stimulator. An SCS with paddle-type leads was placed by a neurosurgeon covering the area from C3 to C5 (Figure 2). On 1-month follow-up, the patient continued to report a good coverage of his pain with no recurrence. Most brachial plexus avulsion injuries are traumatic in origin, mainly caused by motor vehicle accidents or industrial injuries. One of the most serious and disabling consequences of brachial plexus avulsion is chronic pain with an incidence of 80% [1]. Most patients describe the pain as a burning sensation, or similar to pins and needles, or an electric shock. In addition to the constant pain, patients typically complain of periodic sharp paroxysms of pain lasting several seconds [2]. The pain usually begins within days of injury and generally persists [2,3]. The origin of the pain has been attributed to root avulsion and spinal cord deafferentation. It is thought that the lack of sensory input into the spinal cord leads to spontaneous activity of the neurons in the dorsal horn, thereby causing pain [2].
Figure 2 Permanent paddle cervical spinal cord stimulation. This pain is unfortunately very resistant to many forms of therapy. Patients are initially treated medically with a combination of anticonvulsants, antidepressants, nonsteroidal anti-inflammatory drugs, or opioids. Surgical procedures for repair of brachial plexus lesions, like repair with autologous grafts, extraplexual or intraplexual nerve transfers, are reported to help in relieving the pain in some cases [4]. If pain persists despite medical management or surgical repair, other invasive treatment modalities like DREZ lesioning and cervical SCS are indicated. For many, DREZ lesioning is the preferred procedure for treating intractable pain due to brachial plexus avulsion. Several studies show that DREZ lesioning produces excellent pain relief in the early postoperative period with 75% to 98.2% of patients having good results immediately after surgery [5,6]. However, the rate of pain recurrence is very high in long-term follow-up [5,6], with many patients undergoing more DREZ lesioning procedures or alternative treatment modalities like SCS.
Figure 1 Cervical spinal cord stimulation trial.
SCS has been used successfully in the treatment of chronic neuropathic pain conditions like failed back surgery syndrome, complex regional pain syndrome, peripheral nerve lesions, and phantom limb pain. Many articles reported the use of SCS for treatment of pain caused by brachial plexus avulsion. Bennet et al. reported five cases of pain caused by brachial plexus avulsion treated with dorsal column stimulation, where all five patients achieved good or excellent pain relief during 13.5 months of follow-up [7]. Piva et al. reported four cases treated with cervical SCS where all attained significant pain relief [8]. Brill et al. reported two cases 713
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López-Mesonero et al. treated with cervical SCS that achieved significant pain reduction and significant reduction of analgesic drug consumption [9]. Lai et al. reported a case of successful pain reduction with high-cervical SCS in a patient who underwent two failed DREZ lesioning procedures [10]. While Bennet et al., Piva et al., and Brill et al. used SCS without a previous DREZ lesioning, Lai et al. prefer DREZ as the first line of treatment after failure of medical management, as it has lower cost than SCS and good immediate outcome. However, with DREZ lesioning, inaccurate lesions can cause complications such as lower extremity weakness, loss of bowel or bladder function, or sexual dysfunction [5,6], as well as a reported high-recurrence rate [5,6]. Our patient reported a significant reduction in pain, 50% improvement, with placement of the trial stimulator at C3–C6 level and continued to have the same coverage and same reduction in pain level after the surgical placement of the paddle stimulator at C3–C5 level. We placed the stimulator above the level of root avulsion as it appears that spinal cord stimulation primarily affects the dorsal column, the spinothalamic tract and the descending pain inhibitory pathway, Lai et al. also reported a good outcome with placement of high-cervical SCS [10]. In conclusion, cervical SCS can be an effective treatment modality for patients with neuropathic pain from brachial plexus avulsion. We recommend an SCS trial in patients with pain resistant to medical management or those with persisting pain despite surgical repair or DREZ lesioning. We recommend placing the stimulator above the avulsion level. More studies on larger patient populations with longterm follow-up and comparison with other treatment modalities are needed to establish guidelines for the treatment of this group of patients who suffer from a debilitating problem that affects their quality of life and their productivity.
SAMER ABDEL-AZIZ, MD, and AHMED H. GHALEB, MD Department of Anesthesiology and Pain Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
References 1 Bertelli JA, Ghizoni MF. Use of clinical signs and computed tomography myelography findings in detecting and excluding nerve root avulsion in complete brachial plexus palsy. J Neurosurg 2006;105:835–42. 2 Parry CB. Pain in avulsion lesions of the brachial plexus. Pain 1980;9:41–53. 3 Narakas AO. Pain syndromes in brachial plexus injuries. In: Brunelli G, ed. Textbook of Microsurgery. Milan: Masson; 1988:809–16. 4 Bonilla G, Di Masi G, Battaglia D, Otero J, Socolovsky M. Pain and brachial plexus lesions: Evaluation of initial outcomes after reconstructive microsurgery and validation of a new pain severity scale. Acta Neurochir 2011;153:171–6. 5 Samii M, Bear-Henney S, Ludemann W, Tatagiba M, Blomer U. Treatment of refractory pain after brachial plexus avulsion with dorsal root entry zone lesions. Neurosurgery 2001;48:1269–77. 6 Sindou MP. Microsurgical lesioning in the dorsal root entry zone for pain due to brachial plexus avulsion: A prospective series of 55 patients. J Neurosurg 2005;102:1018–28. 7 Bennet MI, Tai YM. Cervical dorsal column stimulation relieves pain of brachial plexus avulsion. J R Soc Med 1994;87:5–6. 8 Piva B, Shaladi A, Saltari R, Gilli G. Spinal cord stimulation in the management of pain from brachial plexus avulsion. Neuromodulation 2003;6:27–31. 9 Brill S, Aryeh I. Neuromodulation in the management of pain from brachial plexus injury. Pain Physician 2008;11:81–5. 10 Lai HY, Lee CY, Lee ST. High cervical spinal cord stimulation after failed dorsal root entry zone surgery for brachial plexus avulsion pain. Surg Neurol 2009;72(3):286–9.
Nummular Headache in a Patient with Craniosynostosis: One More Evidence for a Peripheral Mechanism Dear Editor, Nummular headache (NH) is a normally mild-to-moderate pain felt in a coin-shaped or elliptical area of the head, typically 1 to 6 cm in diameter. The affected area may show several combinations of sensory signs, such as hypoesthesia, paresthesia, dysesthesia, and tenderness 714
[1,2]. In addition, a few patients develop local alopecia or other trophic changes [3]. NH was described in 2002 [1], and has already been reported in 238 cases according to a recent review [4]. Although NH emerged as a primary disorder, we have to pay attention to possible symptomatic or secondary cases. Here we report a case of NH associated with craniosynostosis.
