Stereotactic radiosurgery for movement disorders

Nowadays, functional neurosurgery is an established treatment for movement disorders such as Parkinson's disease, essential tremor, and dystonia. The effectiveness and safety of neuromodulation procedures (deep brain stimulation) replaced in the last years ablative irreversible stereotactic lesions for movement disorders. Stereotactic radiosurgery with gamma knife is a non-invasive form of treatment for movement disorders. The main limitation of stereotactic radiosurgery is the impossibility of electrophysiological confirmation of the target structure. Nevertheless, patients with advanced age and significant medical conditions that preclude classic open stereotactic procedures or patients who must receive anticoagulation therapy may gain great functional benefit using gamma knife stereotactic radiosurgery.     

Neuropsychology for movement disorders neurosurgery

The neuropsychologist plays a crucial role in three phases of the neurosurgical treatment of movement disorder patients, namely screening, outcome evaluation and research. In screening patients, the differential diagnosis of dementia, impact of depression or other psychiatric conditions, and the influence of disease and medication-induced symptoms on cognitive performance must be determined. Postoperatively, systematic evaluations elucidate the cognitive costs or benefits of the procedure. The neuropsychologist is then able to provide feedback and counselling to the professional staff, patient and family to inform management strategies. Neuropsychologists also study alteration of cognitive processing due to lesions or stimulation, which, in tandem with functional imaging, shed light on plasticity in cortical and subcortical processing.     

立体定向手术治疗顽固性中枢神经痛

目的研究脑立体定向手术治疗顽固性中枢神经痛(central pain,CP)的临床应用。方法CP患者6例,包括丘脑及脑桥梗塞4例,丘脑出血1例,丘脑梗塞合并颈髓损伤1例。所有病例均在局麻下行双侧扣带回及双侧伏核(nucleus accumbens,NAc)毁损。手术前后采用视觉模拟评分(visual analog scale,VAS)、McGill疼痛问卷(mcGill pain questionnaire,MPQ),口述描绘评分法(verbal rating scales,VRS)进行评分,同时记录手术前后患者使用镇痛剂的种类和最大剂量。将术后1周,1个月,3个月,6个月的评分和术前比较,采用自身配对t检验。结果术后6例患者从1周到6个月止痛效果较好,最长1例随访18个月,止痛效果稳定,除1例丘脑出血后疼痛患者目前偶尔口腹止痛片外,其余患者到目前为止未用任何麻醉镇痛剂治疗。VAS,MPQ,PPI,VRS评分手术前后差异显著(P<0.01)。结论脑立体定向双侧伏核+双侧扣带回损毁手术治疗CP具有较好的治疗效果,超过1年的长期疗效有待进一步观察。     

Targeting the caudal intralaminar nuclei for functional neurosurgery of movement disorders

The caudal intralaminar nuclei, in particular the Centrum-Medianum Parafascicularis (CM-Pf) nucleus complex, are involved in various functions, particularly in pain processing and in motor control, through their projections to the subthalamic nucleus and their afferents from the pallidum internus (GPi) (or entopeduncular nucleus in the rat). The nociceptive inputs received by the CM-Pf are modulated by the somato-sensory thalamus. The lateral habenula (HbL) receives noxious inputs and has an inhibitory influence on the nigral dopaminergic neurons. CM-Pf and the HbL share comparable response characteristics to noxious inputs and might play comparable, and perhaps complementary, roles in conveying the nociceptive information to the basal ganglia system, thereby modulating motor responses, such as freezing and dyskinesias. The interaction between CM-Pf, HbL, GPi, STN and SNC might provide a new template for high frequency stimulation strategies in the treatment of movement disorders.     

Physiological localisation in functional neurosurgery for movement disorders: a simple approach.

Controversy exists between anatomical methods and single cell recording as the preferred approach in target localisation in functional neurosurgery for movement disorders. The controversy centres on accuracy as compared to practicality. We describe a mapping technique of semi-microstimulation utilising threshold measurements which has been used in 66 procedures in 50 subjects. We compared the accuracy of anatomical localisation with the final chosen target using the above technique. We also compared the benefit, the side effects and the surgical complication rate with published data on single cell recording and anatomical localisation. The mean difference in 3-dimensional space between the anatomical target and the physiological target was 6.85 mm (P < 0.0001). A good response was obtained in 80% of procedures. Mortality was 1.5%. The surgical complication rate was 1.5%. Mild side effects, serious side effects, transient side effects and permanent side effects were evident in 4.5%, 10.6%, 6.1% and 9.1% of procedures. These figures compared better than anatomical studies and similar to single cell recording studies. It is concluded that this approach provides both accuracy and simplicity and is recommended as a compromise to the currently available methods.     

Stereotactic neurosurgery in children and adolescents

Between March 1992 and January 1998, 100 stereotactic procedures were carried out in our Stereotactic Department. Of these, 24 were performed on patients under 18 years of age, 22 of them under a local anaesthetic and sedation. The ages of these patients ranged between 4 months and 18 years. The stereotactic procedures carried out were: 15 cerebral biopsies, 5 iodine-125 implants, 4 implantations of Rickham reservoirs with ventricular catheter, with additional holes to establish a connection between the cyst content and the ventricular system (internal drainage): 2 of these patients had arachnoidal cysts in the pineal region, 1 a thalamic neuroepithelial cyst and 1 a cystic craniopharyngioma, with excellent control of hydrocephalus. All cerebral biopsies were positive, including 3 in which brain stem tumours were detected. Of the 5 patients treated by brachytherapy, 4 had pilocytic astrocytomas and 1 an anaplastic astrocytoma. The sites of the tumours for which implants were used were the thalamus in 4 cases, and the basal ganglia (corpus striatum) in 1. In only 2 cases was there some transistory morbidity, and mortality was nil. The stereotactic procedures in this varied group were well tolerated, with low morbidity and mortality rates, which proves that this method is effective and safe for patients. It can also be used for the diagnosis of brain stem tumours. Midline cysts can also be treated by means of internal drainage with catheters (a minimally invasive form of surgery). Received: 6 November 1998     

Stereotactic hypothalamotomy for behaviour disorders

Posterior hypothalamotomy is a relatively simple stereotactic procedure. The radiological determination of the target and its physiological corroboration by electrical stimulation are accurate. The lesions have always been made in the site of maximum sympathetic response. In this respect, the cardiovascular changes (hypertension and tachycardia), which are always elicited from a more restricted area, are of particular importance. Depth recordings, however, have been less useful. Undesirable side-effects, if present, were mild and transitory. There was no postoperative intelligence deficit, at least with the standard tests.     

立体定向手术治疗药物依赖24例临床分析

目的探讨立体定向手术治疗药物依赖的方法。方法对24例药物依赖病人行立体定向脑深部核团毁损术治疗,靶点为双侧伏隔核各1点,双侧扣带回前部、中部、前部与中部中间各1点。结果病人出院时均符合戒断标准。随访1~6个月,2例复吸,22例正常生活。结论采用立体定向手术治疗药物依赖病人,近期效果肯定,相对安全,长期疗效有待观察。     

Surgical complications of functional neurosurgery treating movement disorders: results with anatomical localisation

Thalamic and pallidal lesions can alleviate movement disorders, but to achieve this safely and efficaciously requires accurate target localization. We report the surgical complications encountered using an anatomical localization technique to create 121 thalamic and pallidal lesions in 79 consecutive patients over a 3 year period. There was no perioperative mortality, although there was one late death indirectly related to surgery. The risk of haemorrhage was 3.3% per lesion made. Anatomical localization offers a relatively safe way of identifying targets for functional neurosurgery, with complication rates which compare favourably with the published literature.     

Deep brain stimulation for movement disorders before DBS for movement disorders

Deep brain stimulation (DBS) is an established surgical treatment for Parkinson’s disease (PD), essential tremor and dystonia. It is generally acknowledged that the development of DBS as we know it today started with the publication of Benabid, Pollak et al in 1987 on thalamic DBS for tremor. This technique gained momentum in the mid-Nineties after that Pollak and Benabid introduced the subthalamic nucleus as a target in advanced PD.This paper reviews the gestational pre-natal era of deep brain stimulation, before 1987. The origin of DBS can be traced back to the practice of intra-operative electrical stimulation, used for target exploration prior to lesioning, during the early years of stereotactic functional neurosurgery. During the 60s, Sem-Jacobsen and others implanted externalised electrodes which were used for intermittent stimulation and evaluation during weeks or months, prior to subsequent ablation of thalamic and other basal ganglia targets. In the early 70s Bechtereva treated PD patients using “therapeutic electrical stimulation” through electrodes implanted for up to 1.5 years. In the late 70s and early 80s the term Deep Brain Stimulation was coined and few groups attempted treatment of Parkinson’s disease, non-Parkinsonian tremor and dystonia with high-frequency stimulation using chronically implanted DBS systems. Cumbersome, un-sophisticated DBS hardware, together with the general decline of all surgery for PD following the introduction of levodopa, may have contributed to the lack of popularity of old-times DBS. It is to the credit of the Grenoble Group to have reinvented, modernised and expanded modern DBS in surgical treatment of movement disorders.     

脑立体定向手术治疗Meige综合征二例报告并文献复习

目的 探讨立体定向深部脑刺激术( DBS)和脑内核团毁损术在Meige综合征(MS)中的临床应用.方法 2例患者术前均采用Burke - Fahn - Marsden肌张力障碍运动评分(BFMDRS),1例MS患者行双侧苍白球内侧核(GPi) DBS手术治疗,1例患者行单侧GPi射频毁损术治疗.结果 行双侧GPi - DBS患者术后随访1年改善达83.7％(BFMDRS评分由术前的22.5分减少为4分),随访2年改善率达69.1％左右(BFMDRS评分由22.5分减少为6分),疗效较为稳定.1例行立体定向右侧GPi毁损术,术后1周疗效明显,BFMDRS从28分减少到6分,改善达78.6％;术后3个月BFMDRS评分为15分,改善率为46.2％,术后6个月随访,所有症状恢复到术前水平.结论 双侧GPi - DBS对于传统治疗无效的Meige综合征患者是一种安全有效的治疗方法;对于不能接受DBS手术的患者,行苍白球或丘脑毁损手术也是值得推荐的一种方法.     

Functional models of movement disorders of basal ganglia origin and effects of functional neurosurgery]

The rate model regarding the development of movement disorders of basal ganglia origin suggests that hyperkinetic and hypokinetic disorders occur as a result of changes in the firing rates in the GPi and SNr, which in turn suppress thalamocortical output. Dopamine depletion in Parkinson's disease increases basal ganglia output, then decreases thalamocortical output, leading to bradykinesia. This model, however, cannot explain a lack of deterioration of parkinsonian signs following thalamic coagulation surgery. Instead of the rate model, the beta oscillation hypothesis has been proposed, explaining that synchronized oscillation in the beta frequency in the basal ganglia disturbs initiation of voluntary movement. We observed that effective high-frequency STN stimulation in parkinsonian monkeys was associated with increase in the firing rate and the pattern shift from irregular burst firing to regular high-frequency firing in the projecting sites. High-frequency neural activation by deep brain stimulation is supposed to cancel lower frequency oscillation including beta oscillation, leading to improvement of bradykinesia. Our observation supports the significance of the neural activity pattern, rather than the tonic activity level, in the development of movement disorders. The rate model cannot explain the improvement of ballismus and chorea by pallidotomy because pallidotomy increases the disinhibition of the thalamocortical projection, which should increase the movements. We observed repetitive bursts or pauses of neuronal firing of the globus pallidus synchronized to ballistic movements in patients with hemiballism or chorea, suggesting that phasic neuronal driving in the basal ganglia is important as their pathophysiology.     

Functional models of movement disorders of basal ganglia origin and effects of functional neurosurgery]

The rate model regarding the development of movement disorders of basal ganglia origin suggests that hyperkinetic and hypokinetic disorders occur as a result of changes in the firing rates in the GPi and SNr, which in turn suppress thalamocortical output. Dopamine depletion in Parkinson's disease increases basal ganglia output, then decreases thalamocortical output, leading to bradykinesia. This model, however, cannot explain a lack of deterioration of parkinsonian signs following thalamic coagulation surgery. Instead of the rate model, the beta oscillation hypothesis has been proposed, explaining that synchronized oscillation in the beta frequency in the basal ganglia disturbs initiation of voluntary movement. We observed that effective high-frequency STN stimulation in parkinsonian monkeys was associated with increase in the firing rate and the pattern shift from irregular burst firing to regular high-frequency firing in the projecting sites. High-frequency neural activation by deep brain stimulation is supposed to cancel lower frequency oscillation including beta oscillation, leading to improvement of bradykinesia. Our observation supports the significance of the neural activity pattern, rather than the tonic activity level, in the development of movement disorders. The rate model cannot explain the improvement of ballismus and chorea by pallidotomy because pallidotomy increases the disinhibition of the thalamocortical projection, which should increase the movements. We observed repetitive bursts or pauses of neuronal firing of the globus pallidus synchronized to ballistic movements in patients with hemiballism or chorea, suggesting that phasic neuronal driving in the basal ganglia is important as their pathophysiology.     

Neuromodulation for movement disorders.

The field of movement disorder surgery is expanding rapidly. This has been accompanied by improvements in neuromodulation technology and neuroimaging, in addition to a realisation that the medical and destructive neurosurgical methods previously employed do not provide an acceptable long-term benefit for many of these patients. The contemporary treatment of Parkinson's disease, dystonia, and other tremulous disorders using deep brain chronic electrical stimulation will be reviewed, and future directions discussed.     

Antisense therapies for movement disorders

Currently, few disease‐modifying therapies exist for degenerative movement disorders. Antisense oligonucleotides are small DNA oligonucleotides, usually encompassing ～20 base pairs, that can potentially target any messenger RNA of interest. Antisense oligonucleotides often contain modifications to the phosphate backbone, the sugar moiety, and the nucleotide base. The development of antisense oligonucleotide therapies spinal muscular atrophy and Duchenne muscular dystrophy suggest potentially wide‐ranging therapeutic applications for antisense oligonucleotides in neurology. Successes with these two diseases have heightened interest in academia and the pharmaceutical industry to develop antisense oligonucleotides for several movement disorders, including, spinocerebellar ataxias, Huntington's disease, and Parkinson's disease. Compared to small molecules, antisense oligonucleotide–based therapies have an advantage because the target disease gene sequence is the immediate path to identifying the therapeutically effective complementary antisense oligonucleotide. In this review we describe the different types of antisense oligonucleotide chemistries and their potential use for the treatment of human movement disorders. © 2019 International Parkinson and Movement Disorder Society     

Zolpidem therapy for movement disorders

Zolpidem is a selective agonist of the benzodiazepine subtype receptor BZ1. The highest density of this receptor is in the output structures of the basal ganglia. The basal ganglia are pathologically involved in many movements disorders. Thus, zolpidem has accumulated attention for a possible drug to treat neurological signs and symptoms in Parkinsonian diseases. In this mini-review, I reviewed effects of zolpidem as movement disorders including Parkinson's disease, progressive supranuclear palsy, dystonia and so on. In addition, I reviewed a possible mechanism of zolpidem for movement disorders.