Long-term tonic spinal cord stimulation in advanced Parkinson's disease: No effect from stimulation under placebo-controlled evaluation.

•Chronic spinal cord stimulation effectiveness was evaluated in four PD patients.•Double blinded cross over evaluation was performed using subthreshold stimulation.•An open label evaluation with regular suprathreshold stimulation was also performed.•No statistically significant effect was produced with either stimulation.•This study highlights the lack of strong clinical evidence supporting SCS for PD.

Exploring clinical outcomes in patients with idiopathic/inherited isolated generalized dystonia and stimulation of the subthalamic region.

BACKGROUND: Deep Brain Stimulation (DBS) is an established treatment option for refractory dystonia, but the improvement among the patients is variable. OBJECTIVE: To describe the outcomes of DBS of the subthalamic region (STN) in dystonic patients and to determine whether the volume of tissue activated (VTA) inside the STN or the structural connectivity between the area stimulated and different regions of the brain are associated with dystonia improvement. METHODS: The response to DBS was measured by the Burke-Fahn-Marsden Dystonia Rating Scale (BFM) before and 7 months after surgery in patients with generalized isolated dystonia of inherited/idiopathic etiology. The sum of the two overlapping STN volumes from both hemispheres was correlated with the change in BFM scores to assess whether the area stimulated inside the STN affects the clinical outcome. Structural connectivity estimates between the VTA (of each patient) and different brain regions were computed using a normative connectome taken from healthy subjects. RESULTS: Five patients were included. The baseline BFM motor and disability subscores were 78.30 ± 13.55 (62.00-98.00) and 20.60 ± 7.80 (13.00-32.00), respectively. Patients improved dystonic symptoms, though differently. No relationships were found between the VTA inside the STN and the BFM improvement after surgery (p = 0.463). However, the connectivity between the VTA and the cerebellum structurally correlated with dystonia improvement (p = 0.003). CONCLUSIONS: These data suggest that the volume of the stimulated STN does not explain the variance in outcomes in dystonia. Still, the connectivity pattern between the region stimulated and the cerebellum is linked to outcomes of patients.

ANTECEDENTES: A estimulação cerebral profunda (ECP) é um tratamento estabelecido para distonias refratárias. Porém, a melhora dos pacientes é variável. OBJETIVO: O objetivo do estudo foi descrever os desfechos da ECP da região do núcleo subtalâmico (NST) e determinar se o volume de tecido ativado (VTA) dentro do NST ou se a conectividade estrutural entre a área estimulada e diferentes regiões cerebrais estão associadas a melhora da distonia. MéTODOS: A resposta da ECP em pacientes com distonia generalizada isolada de etiologia hereditária/idiopática foi mensurada pela escala de Burke-Fahr-Marsden Dystonia Rating Scale (BFM) antes e 7 meses após a cirurgia. A soma dos volumes do NST nos dois hemisférios foi correlacionada com a melhora nos escores do BFM para avaliar se a área estimulada dentro do NST afeta o desfecho clínico. A conectividade estrutural estimada entre o VTA de cada paciente e as diferentes regiões cerebrais foram computadas usando um conectoma normativo retirado de indivíduos saudáveis. RESULTADOS: Cinco pacientes com idade de 40,00 ± 7,30 anos foram incluídos. O BFM motor e de incapacidade basal eram de 78,30 ± 13,55 (62,00­98,00) e 20,60 ± 7,80 (13,00­32,00), respectivamente. Os pacientes melhoraram com a cirurgia, mas com variabilidade. Não houve relação entre o VTA dentro do NST e a melhora do BFM após a cirurgia (p = 0.463). Entretanto, a conectividade estrutural entre o VTA e o cerebelo correlacionaram com a melhora da distonia (p = 0.003). CONCLUSãO: Os dados sugerem que o VTA dentro do NST não explica a variabilidade do desfecho clínico na distonia. Porém, o padrão de conectividade entre a região estimulada e o cerebelo foi relacionada com o desfecho dos pacientes.

Exploring clinical outcomes in patients with idiopathic/inherited isolated generalized dystonia and stimulation of the subthalamic region / Explorando os desfechos clínicos em pacientes com distonia idiopática/hereditária generalizada isolada submetidos a estimulação da região subtalâmica

Abstract Background Deep Brain Stimulation (DBS) is an established treatment option for refractory dystonia, but the improvement among the patients is variable. Objective To describe the outcomes of DBS of the subthalamic region (STN) in dystonic patients and to determine whether the volume of tissue activated (VTA) inside the STN or the structural connectivity between the area stimulated and different regions of the brain are associated with dystonia improvement. Methods The response to DBS was measured by the Burke-Fahn-Marsden Dystonia Rating Scale (BFM) before and 7 months after surgery in patients with generalized isolated dystonia of inherited/idiopathic etiology. The sum of the two overlapping STN volumes from both hemispheres was correlated with the change in BFM scores to assess whether the area stimulated inside the STN affects the clinical outcome. Structural connectivity estimates between the VTA (of each patient) and different brain regions were computed using a normative connectome taken from healthy subjects. Results Five patients were included. The baseline BFM motor and disability subscores were 78.30 ± 13.55 (62.00-98.00) and 20.60 ± 7.80 (13.00-32.00), respectively. Patients improved dystonic symptoms, though differently. No relationships were found between the VTA inside the STN and the BFM improvement after surgery (p = 0.463). However, the connectivity between the VTA and the cerebellum structurally correlated with dystonia improvement (p = 0.003). Conclusions These data suggest that the volume of the stimulated STN does not explain the variance in outcomes in dystonia. Still, the connectivity pattern between the region stimulated and the cerebellum is linked to outcomes of patients.

Resumo Antecedentes A estimulação cerebral profunda (ECP) é um tratamento estabelecido para distonias refratárias. Porém, a melhora dos pacientes é variável. Objetivo O objetivo do estudo foi descrever os desfechos da ECP da região do núcleo subtalâmico (NST) e determinar se o volume de tecido ativado (VTA) dentro do NST ou se a conectividade estrutural entre a área estimulada e diferentes regiões cerebrais estão associadas a melhora da distonia. Métodos A resposta da ECP em pacientes com distonia generalizada isolada de etiologia hereditária/idiopática foi mensurada pela escala de Burke-Fahr-Marsden Dystonia Rating Scale (BFM) antes e 7 meses após a cirurgia. A soma dos volumes do NST nos dois hemisférios foi correlacionada com a melhora nos escores do BFM para avaliar se a área estimulada dentro do NST afeta o desfecho clínico. A conectividade estrutural estimada entre o VTA de cada paciente e as diferentes regiões cerebrais foram computadas usando um conectoma normativo retirado de indivíduos saudáveis. Resultados Cinco pacientes com idade de 40,00 ± 7,30 anos foram incluídos. O BFM motor e de incapacidade basal eram de 78,30 ± 13,55 (62,00-98,00) e 20,60 ± 7,80 (13,00-32,00), respectivamente. Os pacientes melhoraram com a cirurgia, mas com variabilidade. Não houve relação entre o VTA dentro do NST e a melhora do BFM após a cirurgia (p = 0.463). Entretanto, a conectividade estrutural entre o VTA e o cerebelo correlacionaram com a melhora da distonia (p = 0.003). Conclusão Os dados sugerem que o VTA dentro do NST não explica a variabilidade do desfecho clínico na distonia. Porém, o padrão de conectividade entre a região estimulada e o cerebelo foi relacionada com o desfecho dos pacientes.

Safety and Outcomes of Dentate Nucleus Deep Brain Stimulation for Cerebellar Ataxia.

Cerebellar symptoms remain orphan of treatment options despite being prevalent and incapacitating. Investigate whether dentate nucleus deep brain stimulation (DN DBS) is safe and leads to improvements in cerebellar symptoms when compared to sham stimulation. This randomized double-blind crossover pilot trial enrolled five patients with spinocerebellar ataxia type 3 or post-lesion ataxia. Active or sham phases were randomly performed three months apart. The primary outcome was ataxia improvement as measured by the Scale for the Assessment and Rating of Ataxia (SARA) after the active compared to the sham period. Secondary outcome measures included safety and tolerability, the Fahn-Tolosa-Marin Tremor Rating Scale (FTMRS), quality of life measurements, and patients' global impression of change. The effects on ataxia were numerically better in four out of five patients after active versus sham stimulation. The composite SARA score did not change after comparing active to sham stimulation (8.6 ± 3.6 versus 10.1 ± 4.1; p = 0.223). The FTMRS showed significant improvement after active stimulation versus sham (18.0 ± 17.2 versus 22.2 ± 19.5; p = 0.039) as did patients' global impression of change (p = 0.038). The quality of life was not modified by stimulation (p = 0.337). DN DBS was well tolerated without serious adverse events. One patient had the electrode repositioned. DN DBS is a safe and well tolerated procedure that is effective in alleviating cerebellar tremor. In this small cohort of ataxic patients, DN DBS did not achieve statistical significance for ataxia improvement.

Should the Globus Pallidus Targeting Be Refined in Dystonia?

BACKGROUND AND STUDY AIMS: Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is a highly effective therapy for primary generalized and focal dystonias, but therapeutic success is compromised by a nonresponder rate of up to 20%. Variability in electrode placement and in tissue stimulated inside the GPi may explain in part different outcomes among patients. Refinement of the target within the pallidal area could be helpful for surgery planning and clinical outcomes. The objective of this study was to discuss current and potential methodological (somatotopy, neuroimaging, and neurophysiology) aspects that might assist neurosurgical targeting of the GPi, aiming to treat generalized or focal dystonia. METHODS: We selected published studies by searching electronic databases and scanning the reference lists for articles that examined the anatomical and electrophysiologic aspects of the GPi in patients with idiopathic/inherited dystonia who underwent functional neurosurgical procedures. RESULTS: The sensorimotor sector of the GPi was the best target to treat dystonic symptoms, and was localized at its lateral posteroventral portion. The effective volume of tissue activated (VTA) to treat dystonia had a mean volume of 153 mm3 in the posterior GPi area. Initial tractography studies evaluated the close relation between the electrode localization and pallidothalamic tract to control dystonic symptoms.Regarding the somatotopy, the more ventral, lateral, and posterior areas of the GPi are associated with orofacial and cervical representation. In contrast, the more dorsal, medial, and anterior areas are associated with the lower limbs; between those areas, there is the representation of the upper limb. Excessive pallidal synchronization has a peak at the theta band of 3 to 8 Hz, which might be responsible for generating dystonic symptoms. CONCLUSIONS: Somatotopy assessment of posteroventral GPi contributes to target-specific GPi sectors related to segmental body symptoms. Tractography delineates GPi output pathways that might guide electrode implants, and electrophysiology might assist in pointing out areas of excessive theta synchronization. Finally, the identification of oscillatory electrophysiologic features that correlate with symptoms might enable closed-loop approaches in the future.

Dentate nucleus deep brain stimulation: Technical note of a novel methodology assisted by tractography.

BACKGROUND: The cerebellum has emerged as an attractive and promising target for neuromodulation in movement disorders due to its vast connection with important cortical and subcortical areas. Here, we describe a novel technique of deep brain stimulation (DBS) of the dentate nucleus (DN) aided by tractography. METHODS: Since 2015, patients with movement disorders including dystonia, ataxia, and tremor have been treated with DN DBS. The cerebellar target was initially localized using coordinates measured from the fastigial point. The target was adjusted with direct visualization of the DN in the susceptibility-weighted imaging and T2 sequences of the MRI and finally refined based on the reconstruction of the dentatorubrothalamic tract (DRTT). RESULTS: Three patients were treated with this technique. The final target was located in the anterior portion of DN in close proximity to the DRTT, with the tip of the lead on the white matter and the remaining contacts on the DN. Clinical outcomes were variable and overall positive, with no major side effect. CONCLUSION: Targeting the DN based on tractography of the DRTT seems to be feasible and safe. Larger studies will be necessary to support our preliminary findings.

Neurocircuitry of Deep Brain Stimulation for Obsessive-Compulsive Disorder as Revealed by Tractography: A Systematic Review.

Objective: Deep brain stimulation (DBS) was proposed in 1999 to treat refractory obsessive-compulsive disorder (OCD). Despite the accumulated experience over more than two decades, 30-40% of patients fail to respond to this procedure. One potential reason to explain why some patients do not improve in the postoperative period is that DBS might not have engaged structural therapeutic networks that are crucial to a favorable outcome in non-responders. This article reviews magnetic resonance imaging diffusion studies (DTI-MRI), analyzing neural networks likely modulated by DBS in OCD patients and their corresponding clinical outcome. Methods: We used a systematic review process to search for studies published from 2005 to 2020 in six electronic databases. Search terms included obsessive-compulsive disorder, deep brain stimulation, diffusion-weighted imaging, diffusion tensor imaging, diffusion tractography, tractography, connectome, diffusion analyses, and white matter. No restriction was made concerning the surgical target, DTI-MRI technique and the method of data processing. Results: Eight studies published in the last 15 years were fully assessed. Most of them used 3 Tesla DTI-MRI, and different methods of data acquisition and processing. There was no consensus on potential structures and networks underlying DBS effects. Most studies stimulated the ventral anterior limb of the internal capsule (ALIC)/nucleus accumbens. However, the contribution of different white matter pathways that run through the ALIC for the effects of DBS remains elusive. Moreover, the improvement of cognitive and affective symptoms in OCD patients probably relies on electric modulation of distinct networks. Conclusion: Though, tractography is a valuable tool to understand neural circuits, the effects of modulating different fiber tracts in OCD are still unclear. Future advances on image acquisition and data processing and a larger number of studies are still required for the understanding of the role of tractography-based targeting and to clarify the importance of different tracts for the mechanisms of DBS.

Balloon compression vs radiofrequency for primary trigeminal neuralgia: a randomized, controlled trial.

ABSTRACT: Surgical procedures are necessary in up to 50% of trigeminal neuralgia patients. Although radiofrequency (RF) is more widely used, it is associated with high intraprocedural costs and long technical learning time. Other simpler procedures such as balloon compression (BC) require a lower training period and have significant lower costs. We evaluated the effects of BC and RF in pain control in primary trigeminal neuralgia in a randomized, double-blinded, head-to-head trial. Individuals were randomly allocated in 1 of 2 groups: BC and RF. Throughout pain, psychological and quality of life measurements were performed at baseline and after surgery. The main outcome was the worst pain in the last 24 hours (0-10) at 6 months postoperatively. After the inclusion of half of the estimated sample, a preplanned interim analysis was performed when 33 patients (62.1 ± 9.4 y.) completed the study. Pain intensity (confidence interval [CI] 95% 0.6 to 3.8, and -0.6 to 2.2, for BC and RF) did not significantly differ. Complications, interference of pain in daily life (CI 95% -0.1 to 2.3 and -0.4 to 2.3, for BC and RF), neuropathic pain symptoms (CI 95% 1.7 to 3.6 and 3.0 to 5.7, for BC and RF), mood (CI 95% 4.8 to 11.5 and 5.5 to 15.1, BC and RF, respectively), medication use, and quality of life (CI 95% 80.4 to 93.1 and 83.9 to 94.2, for BC and RF) were also not different. Radiofrequency presented more paresthetic symptoms than BC at 30 days after intervention. Based on these results, the study was halted due to futility because BC was not superior to RF.

Microvascular decompression of the posterior inferior cerebellar artery for intermediate nerve neuralgia.

BACKGROUND: Intermediate nerve neuralgia (INN) is an extremely rare craniofacial pain disorder mainly caused by neurovascular compression. CASE DESCRIPTION: We present the case of a 48-year-old female with a 20-month history of intractable paroxysmal INN on the right side. The patient described feeling paroxysmal pain in her auditory canal, pinna, deep in the jaw, and adjacent retromastoid area on the right side. She described the pain as being like a burning sensation. Magnetic resonance imaging showed the right posterior cerebellar artery crossing the cerebellopontine cistern in close contact with the right VII and VIII nerves. Surgical exploration via retromastoid craniotomy revealed vascular compression of the intermediate nerve by the posterior cerebellar artery. We therefore performed microvascular nerve decompression to relieve pain, and the patient remained pain-free at the 6-month follow-up visit. CONCLUSION: INN should be considered as a differential diagnosis in cases with atypical facial neuralgia, and microvascular decompression is an effective treatment option that can provide optimal pain relief.

Liposomal topical capsaicin in post-herpetic neuralgia: a safety pilot study.

UNLABELLED: Topical treatments have gained popularity for general use as an adjunct to systemic drugs in neuropathic pain, but their use produces variable clinical results and local adverse events. OBJECTIVE: To evaluate the safety and analgesic effect of a formulation of liposomal capsaicin (LC) (0.025%) in patients with post herpetic neuralgia (PHN). METHOD: Patients who remained symptomatic after first-and second-line treatment were randomized to receive LC for six weeks in a placebo-controlled, crossover design study. Clinical assessment was performed at baseline, in the second, fourth and sixth week of treatment. RESULTS: Thirteen patients completed both treatment periods. Visual Analog Scale (VAS) was significantly decreased after the end of the study (p = 0.008), however the effect of treatment was not significant (p = 0.076). There was no difference on global impression of change and other pain characteristics. LC was safe and well tolerated. However, at the concentration used, its analgesic effects were marginal and not significant.

Liposomal topical capsaicin in post-herpetic neuralgia: a safety pilot study / Capsaicina lipossomal tópica na neuralgia pós-herpética: um estudo piloto de segurança

Topical treatments have gained popularity for general use as an adjunct to systemic drugs in neuropathic pain, but their use produces variable clinical results and local adverse events. Objective To evaluate the safety and analgesic effect of a formulation of liposomal capsaicin (LC) (0.025%) in patients with post herpetic neuralgia (PHN). Method Patients who remained symptomatic after first-and second-line treatment were randomized to receive LC for six weeks in a placebo-controlled, crossover design study. Clinical assessment was performed at baseline, in the second, fourth and sixth week of treatment. Results Thirteen patients completed both treatment periods. Visual Analog Scale (VAS) was significantly decreased after the end of the study (p = 0.008), however the effect of treatment was not significant (p = 0.076). There was no difference on global impression of change and other pain characteristics. LC was safe and well tolerated. However, at the concentration used, its analgesic effects were marginal and not significant. .

Os tratamentos tópicos ganharam popularidade para uso geral como um adjuvante de medicamentos sistêmicos na dor neuropática, mas seu uso produz resultados clínicos variáveis e eventos adversos locais. Objetivo Avaliar o efeito de segurança e analgesia de uma formulação de capsaicina lipossomal (LC) (0,025%) em pacientes com neuralgia pós-herpética. Método Os pacientes que permaneceram sintomáticos após tratamento de primeira e de segunda linha foram randomizados para receber LC durante seis semanas em um estudo cruzado controlado por placebo. A avaliação clínica foi realizada no início do estudo, na segunda, quarta e sexta semana de tratamento. Resultados Treze pacientes completaram dois períodos de tratamento. Escala Visual Analógica diminuiu significativamente após o final do estudo (p = 0,008), no entanto, o efeito do tratamento não era significativo (p = 0,076). Não houve diferença na impressão global de mudança e de outras características da dor. LC foi segura e bem tolerada. No entanto, para a concentração utilizada, os seus efeitos analgésicos foram marginais e não significativos. .

Management of trigeminal neuralgia in sclerosteosis.

BACKGROUND: Sclerosteosis is a rare bone disorder characterized by a progressive craniotubular hyperostosis. The diagnosis of sclerosteosis is based on characteristic clinical and radiographic features and a family history consistent with autosomal recessive inheritance. The skull overgrowth may lead to lethal elevation of intracranial pressure, distortion of the face, and entrapment of cranial nerves, resulting in recurrent facial palsy or secondary trigeminal neuralgia. CASES DESCRIPTION: The authors reported cases of two siblings who were diagnosed with familial sclerosteosis and presented with secondary trigeminal neuralgia. The patients were 28 and 40-year-old and presented with pain in the right V2-V3 and V3 distributions, respectively. The facial pain was resistant to medications and was treated with percutaneous techniques. The foramen ovale puncture was complicated initially and the difficulty increased over the years due to stenosis of the foramen. CONCLUSION: The treatment of the trigeminal neuralgia secondary to hyperostosis and resistant to medications presents a dilemma. The narrowing of the foramen oval and difficulty in the identifying and approaching of the foramen makes the percutaneous technique a challenge for the neurosurgeon in patients harboring sclerosteosis. Microvascular decompression should not be considered since the primary cause of the trigeminal neuralgia is the nerve entrapment by the narrowing of neurovascular foramina and not the neurovascular conflict related to essential trigeminal neuralgia. Stereotactic radiosurgery may be a good treatment option, but there is a lack of published data supporting the use of this method in cranial hyperostosis.