Intrathecal infusion of drugs for treatment of chronic nonmalignant pain

A infusão intratecal de fármacos analgésicos é método considerado útil no tratamento da dor decorrente do câncer. Entretanto, estudos sobre eficácia no tratamento prolongado da dor crônica não decorrente de câncer são escassos. Este trabalho objetivou analisar prospectivamente o resultado do tratamento de 80 doentes com dor crônica não decorrente de câncer com infusão intratecal de morfina. Os resultados foram avaliados quanto à intensidade, características e etiologias da dor, qualidade de vida e complicações dos procedimentos; 42 doentes eram do sexo masculino, a média das idades foi de 48,4 anos e a duração média da condição álgica foi de 53 meses. A dor decorreu de mielopatia em 26,3% dos doentes, de síndrome dolorosa miofascial em 6,3%, de síndrome dolorosa pós-laminectomia em 23,8%, de síndrome complexa de dor regional em 8,8%, de síndrome fibromiálgica em 13,8% e de neuralgia pós herpética em 5,0%. Apresentavam dor neuropática 49 (61,2%), nociceptiva 19 (23,8%) e mista 12 (15%) pacientes. Foram implantadas 62 bombas de acionamento digital para infusão em bolo e 18 bombas de infusão contínua (gás) ou programável. As médias das intensidades da dor reduziram-se de 9,5 para 4,6 segundo a escala visual analógica (EVA) ao final do acompanhamento que variou de 18 a 98 meses (média = 46,7 meses); houve melhora significativa da dor nos doentes com dor neuropática (p < 0,001), nociceptiva (p < 0,001) ou mista (p = 0,005). Apesar da melhora da qualidade de vida de acordo com SF-36 (30,8 para 49,6) e nas dimensões do Questionário \"Treatment of Pain Survey\" (TOPS), não houve alteração na capacidade objetiva para o trabalho. Não houve diferença significativa entre infusão contínua e em bolo quanto à melhora da dor (p = 0,597). O consumo de morfina estabilizou-se após o sexto mês de tratamento na maioria dos casos. Não houve diferença significativa quanto à melhora em relação à localização da extremidade do cateter subaracnóideo (p = 0,227). Ocorreu agravamento da dor de 4,9 para 8,9 (p < 0,001) durante o período de uso de medicação placebo. Alguns efeitos adversos ocorreram inicialmente e geralmente foram toleráveis. Conclui-se que a infusão intratecal de opióides é método adequado e seguro para o tratamento da dor crônica rebelde não decorrente do câncer.Implantable pumps for intrathecal delivery of opiates are efficient for treatment of cancer pain. However, studies of nonmalignant pain with long term follow-up are few. The present study use prospective analysis of the result of the long term treatment of 80 patients presenting nonmalignant pain with intrathecal infusion of morphine. The nature and etiology of the pain, quantitative and qualitative expressions of pain and the quality of the life before and at the end of the treatment and complications of procedures were evaluated; were male 42 (52%) patients, the average of the ages was 48.4 years and the mean duration of previous pain, 53 months. Pain was due to mielopathy in 26.3% of the cases, myofascial pain syndrome in 6.3%, failed back pain in 23.8%, complex regional pain syndrome in 8.8%, fibromyalgia in 13.8% and post-herpetic neuralgia in 5.0%. Presented as neuropathic pain 49 (61.2%) patients, as nociceptive pain 19 (23.8%) patients and as mixed pain 12 (15%) patients. In 62 patients pumps for self-administration bolus of morphine was implanted and in 18 constant-flow(gas) or programable pumps. The mean intensity of pain according the visual analogical scale (VAS) reduced from 9.5 to 4.6 at the end of 46.7 months (18 to 98 months) mean follow-up; there was significant improvement of the results in neuropathic(p < 0.001), nociceptive(p < 0.001) and mixed pain(p = 0.005). There was improvement of the quality of life measured by SF-36(30.8 to 49.6) and in all dimensions of the Questionnaire \"Treatment of Pain Survey\" (TOPS), except in working capacity. There was no significant difference of the results for patients treated with bolus or constant flow pumps (p = 0.597). The daily dose of morphine became constant after six month of treatment in the majority of the cases. The position of the tip of the cateter did not influenced improvement in pain intensity (p = 0.277). Patients treated with placebo had increasing of pain intensity from 4.9 to 8.9 according the VAS (p < 0,001). Side effects were more frequent at the beginning of the treatment and few were intolerable. Concluded that intrathecal infusion of morphine is a suitable and safe method for treatment of chronic nonmalignant pain

Myoclonus-dystonia syndrome due to GNAO1 mutation: a case report

Introduction: Myoclonus-dystonia syndrome (MDS) is an autosomal-dominant movement disorder characterized by childhood-onset myoclonic jerks and dystonic symptoms. The estimated prevalence for MDS is 1/500.000 and usually it is associated with mutations in the epsilon-sarcoglycan (SGCE) gene. One rarer genetic cause for MDS is the GNAO1 mutation. Cytogenetically located on 16q13, this gene encodes a specific subclass of G protein, a signal-transducing molecule important to the central and peripheral nervous system. This heterotrimeric guanine nucleotide-binding protein is composed of alpha, beta, and gamma subunits. The GNAO1 gene usually encodes for G-alpha-o, one of the four subclasses of the G-alpha subunit. GNAO1 variants can cause a wide clinical spectrum and the two major characteristic features caused by them are early-onset epileptic encephalopathies (EOEEs) and involuntary movements without seizures. Genetic testing for GNAO1 should be considered in patients with EOEE or involuntary movement with severe developmental delay. Objective: Our report is about a 2 years old female patient with MDS due to GNAO1 mutation, a rare genetic condition. The aim of the present case report is to highlight the relevance of genetic testing for GNAO1 in cases of MDS. Case Report: A 2-years-old female patient diagnosed with the Myoclonus-dystonia syndrome due to GNAO1 mutation presented multifocal dystonia and severe myoclonic jerks. GNAO1 is located on chromosome 16 (not X-linked) and the mutation was found by whole exome sequencing. The alteration in the position chr16.56.385.308 resulted from a G to A substitution. The glutamine at codon 246 was replaced with lysine. In addition, the electroencephalogram detected myoclonia with no loss of consciousness. In spite of the absence of epileptic encephalopathy, this neurodevelopmental disorder interferes with her daily tasks, particularly breastfeeding. Low doses of rivotril had been attempted for small periods of time. It is expected that, at the age of six years, she undergoes a neurosurgery to insert DBS (deep brain stimulation) in the internal globus pallidus (GPi). DBS is an effective treatment for even the severe MDS and surgery at an early stage may predict a better outcome

DBS treatment in an 18-year-old with refractory dystonia due to DYT1 mutation: a case report

Introduction: The term dystonia may be defined by abnormal involuntary movements or postures due to sustained or intermittent muscle contractions. One of the most common aetiologies of isolated dystonia is due to the mutation in DYT1 gene, resulting in a disorder of abnormal regulation of gene transcription and neuronal circuit development. Of all the patients with this mutation, about 30-40% will develop symptoms of the disease. Typically, the clinical manifestation of this type of dystonia will begin from the first to third decade of life, with generalized distribution, and involving more likely the lower limbs or, less frequently, the upper limbs and trunk. Objective: To present a case of an infrequent refractory dystonia due to DYT1 gene mutation in an 18-year-old male patient that was later treated with Deep Brain Stimulation (DBS). Case report: Here we report about the case of a 18-year-old male patient affected by torsion dystonia of the neck and a segment of the upper limbs. He first exhibited symptoms when he was 15 years old and, since then, has had a series of complications, such as severe pain and recurrent pneumonia. Genetic analysis identified a DYT1 gene superexpression mutation. Previous therapies had included physiotherapy, botulinum toxin injections, drugs such as primidone and clonazepam, but all with little improvement. Due to the patient's severe torsion dystonia on his right side, it was decided to implant a DBS only in the left internal globus pallidus (GPi) posteromedial area, in a brain surgery with general anesthesia that took place in March 2018. After 10 months, the same procedure was made in the right GPi, at the subthalamic nucleus, aiming to treat his dystonic tremors located in the left part of the body. The electrodes inserted were Medtronic® 3389 and the generator was Activa RC rechargeable, with 0.5 mm spacing. The following programming was set: current of 3 mA, frequency of 130 Hz and pulse width of 90 μs. The battery of the electrode was inserted in the right side of the chest due to the patient's more severe torsion. The post-operative (PO) was successful, without any deficit, being discharged from the hospital at the PO day 4 in the first surgery and day 2 and in the second. After a 2-year follow-up period, the patient presents a normal life compared to the average of his age, without any of the symptoms or complications he had before. He regularly attends physiotherapy and fitness centres to maintain muscle training

Deep brain stimulation in primary Meige’s syndrome: a successful case report

Introduction: Meige’s Syndrome is a rare focal dystonia disorder characterized mainly by blepharospasm and orofacial dystonia. Dystonia is identified as a movement disorder, with abnormal involuntary movements and postures, caused by sustained or intermittent muscle contractions. Its pathophysiology is not fully elucidated, but it is known that its evolution is due to an abnormal excitability of the sensorimotor cortex and the interneural pathways of the brainstem, a genetic predisposition and environmental factors. Treatment includes various interventions, ranging from conservative approaches to invasive surgical procedures. Oral medications such as anticholinergics, dopamine antagonists and GABA receptor agonists shows positive results, also botulinum A injection can be used as treatment. If any of those conservative alternatives are not providing the required results, deep brain stimulation (DBS) of globus pallidus interna (GPi) provides an invasive neuromodulation that has been presenting improvement of symptoms in individuals with previous failure in other forms of treatment. Objectives: The purpose of this case report is to show the effectiveness of treatment with deep brain stimulation of GPi in a patient with Meige Syndrome that has undergone several other approaches previously. Because it is a surgical procedure, there are risks of adverse effects, but most of them can be minimized or even stopped by the correct programming of the intracerebral electrodes. This case report shows that the deep brain stimulation of Gpi is more efficient than other treatments when well indicated, besides having a better index of improvement when compared to the stimulation of the subthalamic nucleus. The authors do not have any conflict of interests. Case report: A 66-years-old man started suffering involuntary contractions of the orofacial muscles associated with blepharospasm that impaired his quality of life. He was diagnosed with Meige syndrome by a neurologist specialized in movement disorders. Before starting the treatment, he was extremely depressed with suicidal ideas and his psycho-affective relationship with family deteriorated since those symptoms started. Therefore, he was under follow-up with a psychologist and psychiatrist, who prescribed antidepressants Duloxetin 30 mg 12/12 oral and Nortriptyline 25 mg 12/12 oral. The patient was unresponsive to the conventional treatment. He had pharmacological treatment with Levodopa, Trazodone and Lorazepam without benefits. He also underwent several botulinum toxin applications for one year and two eyelid lift surgeries, also without success. He was referred to a functional neurosurgeon, who proceeded with the Gpi-DBS implantation in the patient, in February 2021, with an ActivRC generator. The surgery was performed with the patient awake and bilateral microrecording was used to help locate the target. After 4 weeks of surgery and correct programming of the electrodes - 3387 from Medtronic, 130 Hz, 90 PW, 2.5 mA, 1.5 mm2 contact area and 1.5 mm interelectrode spacing, with rechargeable battery -, the patient evolved with an improvement of 80% of the symptoms he presented before the surgical procedure

Endoscopic-guided percutaneous radiofrequency cordotomy

The authors present the first clinical implementation of an endoscopic-assisted percutaneous anterolateral radiofrequency cordotomy. The aim of this article is to demonstrate the intradural endoscopic visualization of the cervical spinal cord via a percutaneous approach to refine the spinal target for anterolateral cordotomy, avoiding undesired trauma to the spinal tissue or injury to blood vessels. Initially, a lateral puncture of the spinal canal in the C1-2 interspace is performed, guided by fluoroscopy. As soon as CSF is reached by the guide cannula (17-gauge needle), the endoscope can be inserted for visualization of the spinal cord and its surrounding structures. The endoscopic visualization provided clear identification of the pial surface of the spinal cord, arachnoid membrane, dentate ligament, dorsal and ventral root entry zone, and blood vessels. The target for electrode insertion into the spinal cord was determined to be the midpoint from the dentate ligament and the ventral root entry zone. The endoscopic guidance shortened the fluoroscopy usage time and no intrathecal contrast administration was needed. Cordotomy was performed by a standard radiofrequency method after refining of the neurophysiological target. Satisfactory analgesia was provided by the procedure with no additional complications or CSF leak. The initial use of this technique suggests that a percutaneous endoscopic procedure may be useful for particular manipulation of the spinal cord, possibly adding a degree of safety to the procedure and improving its effectiveness. (DOI: 10.3171/2010.4.JNS091779

Stereotactic biopsy for intracranial lesions: clinical-pathological compatibility in 60 patients Biopsia estereotáctica para lesões intracranianas: compatibilidade clínico patológica em 60 casos

OBJECTIVE: Image guided stereotactic biopsy (SB) provides cerebral tissue samples for histological analysis from minimal lesions or those that are located in deep regions, being crucial in the elaboration of therapeutic strategies, as well as the prevention of unnecessary neurosurgical interventions. METHOD: Sixty patients with central nervous lesions underwent SB from November 1999 to March 2008. They were followed up to 65 months. Preoperative diagnosis was based on clinical presentation and neuro-radiological features, pathologic diagnosis, clinical outcome. The compatibility of these findings with the pathologic diagnosis was analyzed. RESULTS: Considering diagnosis confirmation when inflammatory hypothesis were made, our accuracy was of 76%, with 94% of those cases having clinic-pathological correspondence after an average of 65.2 months of follow up. Considering diagnosis confirmation with the preoperative hypothesis of neoplasm, our accuracy was of 69% with 90% of these cases having clinic-pathological correspondence after an average of 47.3 months of follow-up. Morbidity rate was of 5% and mortality was zero. The diagnosis rate was 95%. CONCLUSION: Stereotactic biopsy represents a safe and precise method for diagnosis. Anatomic and histopathological analyses have high compatibility with long-term clinical outcome.<br>OBJETIVO: A biopsia estereotáctica (BE) guiada por imagem propicia amostras de tecido cerebral para análises histológicas, sendo decisiva na estratégia terapêutica e prevenção de intervenções neurocirúrgicas desnecessárias. MÉTODO: 60 pacientes com lesões do sistema nervoso central foram submetidos à biópsia estereotáctica no período de novembro de 1999 a março de 2008. Foram analisados a acurácia do método, a capacidade de confirmar o diagnóstico clínico pré-operatório e o comportamento evolutivo com sua compatibilidade com o diagnóstico patológico. RESULTADOS: As três lesões mais freqüentes foram: neoplasias neuroepiteliais, processos inflamatórios e infecções. Considerando a confirmação diagnóstica quando pensava-se em lesão inflamatória, nossa acurácia foi 76%, com 94% destes casos tendo compatibilidade clínico patológica após média de 65,2 meses de acompanhamento. Considerando a confirmação diagnóstica com a hipótese pré-operatória de lesão neoplásica, nossa acurácia foi 69%, com 90% destes casos tendo compatibilidade clínico-patológica após média de 47,3 meses de acompanhamento. O índice de morbidade foi 5%. A mortalidade foi nula e o índice de diagnóstico foi 95%. CONCLUSÃO: A biopsia estereotáctica é um método seguro e preciso para o diagnóstico. O exame anátomo-patológico possui alta compatibilidade com a evolução clínica dos doentes a longo prazo

Reversal of diabetic-induced myopathy by swimming exercise in pregnant rats:a translational intervention study

Gestational diabetes mellitus (GDM) plus rectus abdominis muscle (RAM) myopathy predicts long-term urinary incontinence (UI). Atrophic and stiff RAM are characteristics of diabetes-induced myopathy (DiM) in pregnant rats. This study aimed to determine whether swimming exercise (SE) has a therapeutic effect in mild hyperglycemic pregnant rats model. We hypothesized that SE training might help to reverse RAM DiM. Mild hyperglycemic pregnant rats model was obtained by a unique subcutaneous injection of 100 mg/kg streptozotocin (diabetic group) or citrate buffer (non-diabetic group) on the first day of life in Wistar female newborns. At 90 days of life, the rats are mated and randomly allocated to remain sedentary or subjected to a SE protocol. The SE protocol started at gestational day 0 and consisted of 60 min/day for 6 days/week in a period of 20 days in a swim tunnel. On day 21, rats were sacrificed, and RAM was collected and studied by picrosirius red, immunohistochemistry, and transmission electron microscopy. The SE protocol increased the fiber area and diameter, and the slow-twitch and fast-twitch fiber area and diameter in the diabetic exercised group, a finding was also seen in control sedentary animals. There was a decreased type I collagen but not type III collagen area and showed a similar type I/type III ratio compared with the control sedentary group. In conclusion, SE during pregnancy reversed the RAM DiM in pregnant rats. These findings may be a potential protocol to consider in patients with RAM damage caused by GDM