Rubens Gisbert Cury

Effects of deep brain stimulation on pain and other nonmotor symptoms in Parkinson disease

Objective: To prospectively evaluate the effect of subthalamic nucleus deep brain stimulation (STN-DBS) on the different characteristics of pain and other nonmotor symptoms (NMS) in patients with Parkinson disease (PD). Methods: Forty-four patients with PD and refractory motor symptoms were screened for STN-DBS. Patients were evaluated before and 1 year after surgery. The primary outcome was change in pain prevalence after surgery. Secondary outcome measures were changes in motor function (Unified Parkinsons Disease Rating Scale), characteristics of pain and other NMS using specific scales and questionnaires, and quality of life. Results: Forty-one patients completed the study. The prevalence of pain changed from 70% to 21% after surgery (p < 0.001). There were also significant improvements in pain intensity, NMS, and quality of life after STN-DBS (p < 0.05). Dystonic and musculoskeletal pain responded well to DBS, while central pain and neuropathic pain were not influenced by surgery. There was a strong correlation between the change in pain intensity and the improvement in quality of life (r = 0.708, p < 0.005). No correlation was found between pain improvement and preoperative response to levodopa or motor improvement during stimulation (r = 0.247, p = 0.197 and r = 0.249, p = 0.193, respectively) or with changes in other NMS. Conclusions: STN-DBS decreased pain after surgery, but had different effects in different types of PD-related pain. Motor and nonmotor symptom improvements after STN-DBS did not correlate with pain relief. Classification of evidence: This study provides Class IV evidence that in patients with idiopathic PD with refractory motor fluctuations, STN-DBS decreases the prevalence of pain and improves quality of life.

Sensory abnormalities and pain in Parkinson disease and its modulation by treatment of motor symptoms.

Pain and sensory abnormalities are present in a large proportion of Parkinson disease (PD) patients and have a significant negative impact in quality of life. It remains undetermined whether pain occurs secondary to motor impairment and to which extent it can be relieved by improvement of motor symptoms. The aim of this review was to examine the current knowledge on the mechanisms behind sensory changes and pain in PD and to assess the modulatory effects of motor treatment on these sensory abnormalities. A comprehensive literature search was performed. We selected studies investigating sensory changes and pain in PD and the effects of levodopa administration and deep brain stimulation (DBS) on these symptoms. PD patients have altered sensory and pain thresholds in the off‐medication state. Both levodopa and DBS improve motor symptoms (i.e.: bradykinesia, tremor) and change sensory abnormalities towards normal levels. However, there is no direct correlation between sensory/pain changes and motor improvement, suggesting that motor and non‐motor symptoms do not necessarily share the same mechanisms. Whether dopamine and DBS have a real antinociceptive effect or simply a modulatory effect in pain perception remain uncertain. These data may provide useful insights into a mechanism‐based approach to pain in PD, pointing out the role of the dopaminergic system in pain perception and the importance of the characterization of different pain syndromes related to PD before specific treatment can be instituted.

Sleep disorder, chorea, and dementia associated with IgLON5 antibodies

A novel syndrome characterized by a distinctive sleep disorder accompanied by variable symptoms of brainstem involvement and a highly restricted haplotype was recently described in association with antibodies to a neuronal cell adhesion protein named IgLON5. Because of the symptoms and chronic disease progression, most of these patients are primarily seen by specialists in sleep and neurodegenerative disorders. Since the initial description of this encephalopathy in 2014, only 1 additional patient has been reported.1 In order to improve clinical recognition we report a new patient who presented with the characteristic sleep dysfunction and subsequently developed chorea.

Spinal cord stimulation improves gait in patients with Parkinson's disease previously treated with deep brain stimulation

Deep brain stimulation and levodopatherapy ameliorate motor manifestations in Parkinsons disease, but their effects on axial signs are not sustained in the long term.

Spinal cord stimulation for Parkinson's disease: a systematic review

Axial symptoms are a late-developing phenomenon in the course of Parkinson’s disease (PD) and represent a therapeutic challenge given their poor response to levodopa therapy and deep brain stimulation. Spinal cord stimulation (SCS) may be a new therapeutic approach for the alleviation of levodopa-resistant motor symptoms of PD. Our purpose was to systematically review the effectiveness of SCS for the treatment of motor symptoms of PD and to evaluate the technical and pathophysiological mechanisms that may influence the outcome efficacy of SCS. A comprehensive literature search was conducted using electronic databases for the period from January 1966 through April 2014. The methodology utilized in this work follows a review process derived from evidence-based systematic review and meta-analysis of randomized trials described in the PRISMA statement. Reports examining SCS for the treatment of PD are limited. Eight studies with a total of 24 patients were included in this review. The overall motor score of the Unified Parkinson’s Disease Rating Scale in the on/off-stimulation condition remained unchanged in 6 patients and improved in 18 patients after SCS. SCS appears to yield positive results for PD symptoms, especially for impairments in gait function and postural stability. However, evidence is limited and long-term prospective studies will be required to identify the optimal candidates for SCS and the best parameters of stimulation and to fully characterize the effects of stimulation on motor and nonmotor symptoms of PD.

Deep brain stimulation of the dentate nucleus improves cerebellar ataxia after cerebellar stroke

The cerebrocerebellum receives input from the cerebral cortex and projects to the motor and premotor cortices and the ventrolateral nucleus of the thalamus via the dentate nucleus (DN). Dentothalamocortical projections modulate the activity of the contralateral primary motor (M1) cortex and are involved in movement planning. Acute ischemic injury of the cerebellar nuclei leads to ataxia and a loss of physiologic excitatory inputs from the DN to the contralateral M1 cortex.1 However, chronic cerebellar ischemic lesions have been associated with a reemerging decrease in intracortical inhibition (ICI) in the contralesional M1, leading to marked interhemispheric asymmetry in cortical excitability, which could account for the functional impairment observed after strokes.2

Long-term improvement of tremor and ataxia after bilateral DBS of VoP/zona incerta in FXTAS

Fragile X-associated tremor/ataxia syndrome (FXTAS) is an X-linked adult-onset neurodegenerative disorder that affects carriers of the fragile X mental retardation 1 (FMR1) gene premutation, which is a 55–200 CGG repeat expansion in the 5ʹ untranslated region of the gene.1 The core symptoms of FXTAS are progressive intention tremor and cerebellar ataxia. These symptoms can be disabling and, when combined, severely reduce the patients quality of life. Symptomatic control with medication has limited effects.1 Very few cases have been treated with deep brain stimulation (DBS), mostly in the ventrointermediate thalamic (VIM) nucleus. This treatment results in tremor improvement with either no benefit or worsening of the ataxia and balance.2–4 We present a patient who experienced long-term tremor control and ataxia improvement after chronic bilateral stimulation of the ventro-oralis posterior thalamic nucleus and zona incerta (VoP/ZI), which resulted in significant improvement in daily life activities.

Neuronavigation-guided transcranial magnetic stimulation of the dentate nucleus improves cerebellar ataxia: A sham-controlled, double-blind n = 1 study

Lesions of the cerebellum can lead to hypotonia, ataxia, intention tremor, and dystonia [1], which can be disabling and resistant to conventional treatments. The cerebrocerebellum receives input exclusively from the cerebral cortex (via pontine nuclei) and projects to the motor, premotor, and prefrontal cortices and to the ventrolateral nucleus of the thalamus via the dentate nucleus. It is involved in motor planning, motor learning, and fine-tuning of the motor activity, mainly by evaluating disparities between intention and action during the execution of movement. Cerebellar projectionsmodulate activity in the contralateral primarymotor cortex (M1) through dentothalamocortical projections. Acute ischemic damage to the deep cerebellar nuclei is known to result in ataxia and loss of excitatory input to the contralateral M1 cortex [1]. However, chronic cerebellar ischemic lesions have recently been associated with reemerging increase in intracortical inhibition in the contralesional M1, leading to marked inter-hemispheric asymmetry in cortical excitability, which could account for part of the functional impairment seen after stroke [2]. We report a case of post-surgical unilateral cerebellar infarction leading to dystonia, intention tremor, and ataxia treated by inhibitory low-frequency neuronavigated repetitive transcranial magnetic stimulation (rTMS) to the healthy cerebellar hemisphere. The aim was to decrease the functional cortical asymmetry related to chronic cerebellar infarction [2]. We hypothesized that this treatment would balance the functional asymmetry seen between both M1 after chronic cerebellar and attenuate clinical symptoms. A 50-year-old female underwent a resection of a right acoustic neuroma in 2006, which was complicated by ischemia of the right cerebellar hemisphere (Fig. 1A). She developed severe axial and appendicular ataxia, mostly on the right, with significant impairment in functioning. A few months later, she developed bilateral involuntary hand and cervical dystonia (documented by electroneuromyographic study), which was refractory to medical treatment. Several treatments were attempted for the cerebellar tremor, including: physical therapy, benzodiazepines, biperidene, beta-adrenergic blocking agents, and primidone, without satisfactory symptomatic improvement. The patient declined deep brain stimulation for symptomatic tremor control. Because of the refractory nature of the symptoms, the subject consented to neuronavigated low-frequency TMS to the healthy dentate nucleus. A double-blind sham-controlled trial of 1 Hz neuronavigated rTMSwas performed on the left dentate nucleus with a refrigerated double-cone rTMS coil (cooled DB-80, Magventure TonikaElektronik, Denmark), which allows for the stimulation of deep structures up to 4e5 cm from the coil center. The dentate nucleus lay 50 mm deep from the skull surface, a distance similar to that of the skull vertex to the leg area at M1 (48 mm) (Fig. 1B). We detected the “hot spot” for M1 distal leg representation (peroneus longus muscle), and then its rest motor threshold was measured. The left dentate nucleus was then targeted by neuronavigation and a 1500-pulse session of either active or sham stimulation was performed at 90% of the rest motor threshold of the leg M1 area. Two (active or sham) stimulation sessions were randomly performed four weeks apart. Clinical assessment and video recording were performed using validated tools before stimulation and one week after by movement disorder specialist blinded to the study. After the active session, there was improvement in tremor (Fahn, Tolosa, Marin Tremor Rating Scale before 1⁄4 38/144; after 1⁄4 24/ 144 37% reduction) and in cerebellar ataxia (scale for the assessment and rating of ataxia [SARA] before 1⁄4 25.5/40, after 1⁄4 17/40) (see video). The Patient Global Impression of Change (measured on a seven-point Leikert scale ranging from 1 to 7) was 6 after the active session (i.e. moderately improved) and 3 after the sham procedure (i.e. no change). There was no change in her dystonia after active treatment (Unified Dystonia Rating Scale 1⁄4 9/112 before, and 9/112 after active stimulation). There was no clinical improvement after sham stimulations using the same rating scales Table 1. Supplementary data related to this article can be found online at http://dx.doi.org/10.1016/j.parkreldis.2015.05.010.

Effects of cerebellar neuromodulation in movement disorders: A systematic review

BACKGROUND The cerebellum is involved in the pathophysiology of many movement disorders and its importance in the field of neuromodulation is growing. OBJECTIVES To review the current evidence for cerebellar modulation in movement disorders and its safety profile. METHODS Eligible studies were identified after a systematic literature review of the effects of cerebellar modulation in cerebellar ataxia, Parkinsons disease (PD), essential tremor (ET), dystonia and progressive supranuclear palsy (PSP). Neuromodulation techniques included transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS). The changes in motor scores and the incidence of adverse events after the stimulation were reviewed. RESULTS Thirty-four studies were included in the systematic review, comprising 431 patients. The evaluation after stimulation ranged from immediately after to 12 months after. Neuromodulation techniques improved cerebellar ataxia due to vascular or degenerative etiologies (TMS, tDCS and DBS), dyskinesias in PD patients (TMS), gross upper limb movement in PD patients (tDCS), tremor in ET (TMS and tDCS), cervical dystonia (TMS and tDCS) and dysarthria in PSP patients (TMS). All the neuromodulation techniques were safe, since only three studies reported the existence of side effects (slight headache after TMS, local skin erythema after tDCS and infectious complication after DBS). Eleven studies did not mention if adverse events occurred. CONCLUSIONS Cerebellar modulation can improve specific symptoms in some movement disorders and is a safe and well-tolerated procedure. Further studies are needed to lay the groundwork for new researches in this promising target.

Unilateral non traumatic vertebral artery dissection with cervical spinal cord infarction

A 45-year old male patient with diabetes presented neck pain with paresthesia and paresis in upper limbs. Physical examination: proximal paraparesis, hyporeflexia and hypoesthesia in the upper limbs. MRI: ischemia in the right hemi-spinal cord (Fig 1), associated to right vertebral artery (VA) dissection (Fig 2). Although more frequently VA dissection causes transient ischemic attack or stroke1, there are few reported cases of ischemia of the cervical cord. VA branches may feed the cervical part of the anterior spinal artery on one or both sides and its occlusion by VA dissection may cause hypoperfusion in this territory2.