Subthalamic deep brain stimulation for Parkinson’s disease outcome

The bilateral effects of deep brain stimulation (DBS) on motor and non-motor symptoms of Parkinson’s disease (PD) have been extensively studied and reviewed. However, the unilateral effects-in particular, the potential lateralized effects of left- versus right-sided DBS-have not been adequately recognized or studied.

Lin et al. summarized the current evidence and controversies in the literature regarding the lateralized effects of DBS on motor and non-motor outcomes in PD patients. Publications in the English language before February 2021 were obtained from the PubMed database and included if they directly compared the effects of unilateral versus contralateral side DBS on the motor or non-motor outcomes in PD. The current literature is overall of low-quality and is biased by various confounders. Researchers have investigated mainly PD patients receiving subthalamic nucleus (STN) DBS while the potential lateralized effects of globus pallidus internus (GPi) DBS have not been adequately studied. Evidence suggests potential lateralized effects of STN DBS on axial motor symptoms and deleterious effects of left-sided DBS on language-related functions, in particular, the verbal fluency, in PD. The lateralized DBS effects on appendicular motor symptoms as well as other neurocognitive and neuropsychiatric domains remain inconclusive. Future studies should control for varying methodological approaches as well as clinical and DBS management heterogeneities, including symptom laterality, stimulation parameters, location of active contacts, and lead trajectories. This would contribute to improved treatment strategies such as personalized target selection, surgical planning, and postoperative management that ultimately benefit patients 1).


The surgical and clinical outcomes of asleep DBS for Parkinson’s disease are comparable to those of awake DBS 2).


Suboptimal targeting within the STN can give rise to intolerable sensorimotor side effects, such as dysarthria, contractions and paresthesias 3) 4) 5). eye movement perturbations, and psychiatric symptoms 6) 7) 8), limiting the management of motor symptoms. The small size of the STN motor territory and the consequences of spreading current to immediately adjacent structures obligate precise targeting. Neurosurgeons therefore rely on a combination of imaging, electrophysiology, kinesthetic responses, and stimulation testing to accurately place the DBS lead into the sensorimotor domain of STN 9) 10) 11).

Deep Brain Stimulation has been associated with post-operative neuropsychology changes, especially in verbal memory.

Deep brain stimulation (DBS) of subthalamic nucleus (STN) is widely accepted to treat advanced Parkinson disease (PD). However, published studies were mainly conducted in Western centers 12).

High frequency subthalamic nucleus (STN) deep brain stimulation (DBS) improves the cardinal motor signs of Parkinson’s disease (PD) and attenuates STN alpha/beta band neural synchrony in a voltage-dependent manner. While there is a growing interest in the behavioral effects of lower frequency (60 Hz) DBS, little is known about its effect on STN neural synchrony.

Low-frequency stimulation of the subthalamic nucleus via the optimal contacts is effective in improving overall motor function of patients with Parkinson Disease 13). In Parkinson’s disease significantly improved important aspects of QoL as measured by PDQ-39. The improvements were maintained at 2 years follow-up except for social support and communication. Sobstyl et al., demonstrated a positive correlation between changes in the off condition of motor UPDRS scores and Unified Dyskinesia Rating Scale in several PDQ-39 dimensions, whereas fluctuation UPDRS scores were negatively correlated with PDQ-39 mobility scores 14).

The degree of clinical improvement achieved by deep brain stimulation (DBS) is largely dependent on the accuracy of lead placement.

A study reports on the evaluation of intraoperative MRI (iMRI) for adjusting deviated electrodes to the accurate anatomical position during DBS surgery and acute intracranial changes 15).


Although dementia is a contraindication in deep brain stimulation for Parkinson’s disease, the concept is supported by little scientific evidence. Moreover, it is unclear whether PD with mild cognitive impairment (PD-MCI) or domain-specific cognitive impairments affect the outcome of DBS in non-demented PD patients.

Baseline cognitive levels of patients with PD who underwent DBS were classified into PD with dementia (PDD) (n = 15), PD-MCI (n = 210), and normal cognition (PD-NC) (n = 79). The impact of the cognitive level on key DBS outcome measures [mortality, nursing home admission, progression to Hoehn&Yahr (HY) stage 5 and progression to PDD] were analyzed using Cox regression models. Park et al. also investigated whether impairment of a specific cognitive domain could predict these outcomes in non-demented patients.

Results: Patients with PDD showed a substantially higher risk of nursing home admission and progression to HY stage 5 compared with patients with PD-MCI [hazard ratio (HR) 4.20, P = .002; HR = 5.29, P < .001] and PD-NC (HR 7.50, P < .001; HR = 7.93, P < .001). MCI did not alter the prognosis in patients without dementia, but those with visuospatial impairment showed poorer outcomes for nursing home admission (P = .015), progression to HY stage 5 (P = .027) and PDD (P = .006).

Conclusions: Cognitive profiles may stratify the pre-operative risk and predict long-term outcomes of DBS in PD 16).


1)

Lin Z, Zhang C, Li D, Sun B. Lateralized effects of deep brain stimulation in Parkinson’s disease: evidence and controversies. NPJ Parkinsons Dis. 2021 Jul 22;7(1):64. doi: 10.1038/s41531-021-00209-3. PMID: 34294724.
2)

Wang J, Ponce FA, Tao J, Yu HM, Liu JY, Wang YJ, Luan GM, Ou SW. Comparison of Awake and Asleep Deep Brain Stimulation for Parkinson’s Disease: A Detailed Analysis Through Literature Review. Neuromodulation. 2019 Dec 12. doi: 10.1111/ner.13061. [Epub ahead of print] Review. PubMed PMID: 31830772.
3) , 10)

Benabid AL, Chabardes S, Mitrofanis J, Pollak P: Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson’s disease. Lancet Neurol 8:67–81, 2009
4) , 11)

Groiss SJ, Wojtecki L, Südmeyer M, Schnitzler A: Deep brain stimulation in Parkinson’s disease. Ther Adv Neurol Disorder 2:20–28, 2009
5)

Zhang S, Zhou P, Jiang S, Wang W, Li P: Interleaving subthalamic nucleus deep brain stimulation to avoid side effects while achieving satisfactory motor benefits in Parkinson disease: a report of 12 cases. Medicine (Baltimore) 95:e5575, 2016
6)

Kulisevsky J, Berthier ML, Gironell A, Pascual-Sedano B, Molet J, Parés P: Mania following deep brain stimulation for Parkinson’s disease. Neurology 59:1421–1424, 2002
7)

Mallet L, Schüpbach M, N’Diaye K, Remy P, Bardinet E, Czernecki V, et al: Stimulation of subterritories of the subthalamic nucleus reveals its role in the integration of the emotional and motor aspects of behavior. Proc Natl Acad Sci U S A 104:10661–10666, 2007
8)

Raucher-Chéné D, Charrel CL, de Maindreville AD, Limosin F: Manic episode with psychotic symptoms in a patient with Parkinson’s disease treated by subthalamic nucleus stimulation: improvement on switching the target. J Neurol Sci 273:116–117, 2008
9)

Abosch A, Timmermann L, Bartley S, Rietkerk HG, Whiting D, Connolly PJ, et al: An international survey of deep brain stimulation procedural steps. Stereotact Funct Neurosurg 91:1–11, 2013
12)

Chiou SM, Lin YC, Huang HM. One-year Outcome of Bilateral Subthalamic Stimulation in Parkinson Disease: An Eastern Experience. World Neurosurg. 2015 Jun 10. pii: S1878-8750(15)00709-3. doi: 0.1016/j.wneu.2015.06.002. [Epub ahead of print] PubMed PMID: 26072454.
13)

Khoo HM, Kishima H, Hosomi K, Maruo T, Tani N, Oshino S, Shimokawa T, Yokoe M, Mochizuki H, Saitoh Y, Yoshimine T. Low-frequency subthalamic nucleus stimulation in Parkinson’s disease: A randomized clinical trial. Mov Disord. 2014 Jan 21. doi: 10.1002/mds.25810. [Epub ahead of print] PubMed PMID: 24449169.
14)

Sobstyl M, Ząbek M, Górecki W, Mossakowski Z. Quality of life in advanced Parkinson’s disease after bilateral subthalamic stimulation: 2 years follow-up study. Clin Neurol Neurosurg. 2014 Sep;124:161-5. doi: 10.1016/j.clineuro.2014.06.019. Epub 2014 Jun 23. PubMed PMID: 25051167.
15)

Cui Z, Pan L, Song H, Xu X, Xu B, Yu X, Ling Z. Intraoperative MRI for optimizing electrode placement for deep brain stimulation of the subthalamic nucleus in Parkinson disease. J Neurosurg. 2016 Jan;124(1):62-9. doi: 10.3171/2015.1.JNS141534. Epub 2015 Aug 14. PubMed PMID: 26274983.
16)

Park KW, Jo S, Kim MS, et al. Cognitive profile as a predictor of the long-term outcome after deep brain stimulation in Parkinson’s disease [published online ahead of print, 2020 Jul 28]. J Neurol Sci. 2020;417:117063. doi:10.1016/j.jns.2020.117063

Pediatric cerebrovascular disease epidemiology

Pediatric cerebrovascular disease epidemiology

The incidence of pediatric stroke is 1 in 5000, and if hemiplegic cerebral palsy due to vaso-occlusive stroke is included, the number could be as high as 1 in 3000. Additionally, cerebrovascular disease is 1 of the top 10 causes of death in infants younger than 1 year. Finally, 20% to 30% of children with arterial ischemic stroke will have recurrent strokes, even with treatment. Stroke in children differs from stroke in adults. Not only is it rare, but its presentation is subtle—particularly in infants—and even with a focal hemiplegia there is a wide differential diagnosis. Coagulation mechanisms, the arteries, and the neurological systems are all different in children, and each of these plays a large role in stroke. The causes of pediatric stroke do not include atherosclerosis, so a myriad of other risk factors and associations exist and are unique for each age group. The causes of pediatric stroke are poorly understood, and although this is a fertile area of research, clinical trials in the field are lacking. Currently, any treatment guidelines or tools being used to treat children with stroke either come from the field of adult stroke or are based on empirical information.

More than 95% of children with ischemic stroke have an underlying thrombus occluding an artery or a vein, and our understanding of clot pathogenesis in children is increasing. Whereas in adults, platelet clots predominantly form secondary to atherosclerosis, in children and infants there is likely a higher fibrin composition, which may require a different treatment strategy. Although anticoagulation is typically used, it is not known whether anticoagulation is more effective than aspirin. There are also major clinical challenges, the most significant of which is that the diagnosis is not made and the stroke is missed entirely or that the diagnosis is severely delayed and by the time the diagnosis is made, the infarct is much larger 1).


In 1978 A 10-year review of the Mayo Clinic experience with childhood cerebrovascular disease unrelated to birth, intracranial infection, or trauma identified 69 patients (38 with ischemic stroke, and 31 with subarachnoid or intracerebral hemorrhage). Although children with cerebral infarction had better survival, they experienced more residual disability than children with cerebral hemorrhage. The medical records-linkage system for Rochester, Minnesota residents made it possible for the first time to study cerebrovascular disease in a well-defined childhood population. Records from all medical facilities serving this population (average of 15,834 resident children) showed four strokes over 10 years (average annual incidence rate of 2.52 cases per 100,000 per year) 2).


In 2018 a study reported the period prevalence, incidence, and risk factors of pediatric stroke in Taiwan.

All Taiwan inhabitants aged 1 month to 18 years registered in the National Health Insurance Research Database between 2010 and 2011 were enrolled in this study. Factors including age, sex, location, and household income levels were collected. Incidence, period prevalence, mortality rate, and the possible risks were completely evaluated. Outcomes and results: Hemorrhagic stroke has a significantly higher mortality rate than ischemic stroke (27.6% vs. 10.2%, P<0.05). Risk factors or underlying diseases for stroke were identified in 77.8% of the patients and 16.2% had more than one risk factor. The most common risk factors were vascular diseases (26.3%), infection (14.0%), and cardiac disorders (9.1%).

Infants younger than 2 years, boys, and children in lower socioeconomic status have a significantly higher risk of stroke. Hemorrhagic stroke has a significantly higher mortality rate than ischemic stroke. More than half of the children with stroke had underlying diseases and the causes of hemorrhagic stroke are significantly different from ischemic stroke 3).


In 2019 Surmava et al. sought to evaluate in -Ontario, the incidence and characteristics of pediatric stroke and TIA including care gaps and the predictive value of International Classification of Diseases (ICD) codes.

A retrospective chart review was conducted at 147 Ontario pediatric and adult acute care hospitals. Pediatric stroke and TIA cases (age < 18 years) were identified using ICD-10 code searches in the 2010/11 Canadian Institute for Health Information’s Discharge Abstract Database (CIHI-DAD) and National Ambulatory Care Reporting System (NACRS) databases in the Ontario Stroke Audit.

Among 478 potential pediatric strokes and TIA cases identified in the CIHI-DAD and NACRS databases, 163 were confirmed as cases of stroke and TIA during the 1-year study period. The Ontario stroke and TIA incidence rate was 5.9 per 100,000 children (3.3 ischemic, 1.8 hemorrhagic, and 0.8 TIA). The mean age was 6.4 years (16% neonate). Nearly half were not imaged within 24 h of arrival in emergency and only 56% were given antithrombotic treatment. At discharge, 83 out of 121 (69%) required health care services post-discharge. Overall positive predictive value (PPV) of ICD-10 stroke and TIA codes was 31% (range 5-74%) and yield ranged from 2.4 to 29% for acute stroke or TIA event; code I63 achieved maximal PPV and yield.

This population-based study yielded a higher incidence rate than prior North-American studies. Important care gaps exist including delayed diagnosis, lack of expert care, and departure from published treatment guidelines. Variability in ICD PPV and yield underlines the need for prospective data collection and for improving the pediatric stroke and TIA coding processes 4).


It is believed that the incidence in the Hospital Universitario “Dr. Jose Eleuterio Gonzalez,” Universidad Autonoma de Nuevo Leon, Monterrey, Nuevo Leon, Mexico is higher than it appears.

A study by Garza-Alatorre et al. aimed to assess the incidence and characteristics of pediatric stroke in this university hospital. Likewise, this study seeks to evaluate if a longer symptoms-to-diagnosis time is associated with mortality in patients with ischemic stroke.

Methods: A retrospective study including children with stroke admitted to the UANL University Hospital from January 2013 to December 2016.

Results: A total of 41 patients and 46 stroke episodes were admitted. About 45.7% had an ischemic stroke and 54.3% had a hemorrhagic stroke. Mortality of 24.4% and morbidity of 60.9% were recorded. Regarding ischemic and hemorrhagic stroke, and increased symptoms-to-diagnosis time and a higher mortality were obtained with a relative risk of 2.667 (95% confidence interval [CI]: 1.09-6.524, p = 0.013) and 8.0 (95% CI: 2.18-29.24, p = < 0.0001), respectively. A continuous increase in the incidence rate, ranging from 4.57 to 13.21 per 1,000 admissions comparing the first period (2013) versus the last period (2016), p = 0.02, was found in our center.

Pediatric stroke is a rare disease; however, its incidence shows a continuous increase. More awareness toward pediatric stroke is needed 5).


1)

Bowers KJ, Deveber GA, Ferriero DM, Roach ES, Vexler ZS, Maria BL. Cerebrovascular disease in children: recent advances in diagnosis and management. J Child Neurol. 2011 Sep;26(9):1074-100. doi: 10.1177/0883073811413585. Epub 2011 Jul 21. PMID: 21778188; PMCID: PMC5289387.
2)

Schoenberg BS, Mellinger JF, Schoenberg DG. Cerebrovascular disease in infants and children: a study of incidence, clinical features, and survival. Neurology. 1978 Aug;28(8):763-8. doi: 10.1212/wnl.28.8.763. PMID: 567292.
3)

Chiang KL, Cheng CY. Epidemiology, risk factors and characteristics of pediatric stroke: a nationwide population-based study. QJM. 2018 Jul 1;111(7):445-454. doi: 10.1093/qjmed/hcy066. PMID: 29648667.
4)

Surmava AM, Maclagan LC, Khan F, Kapral MK, Hall RE, deVeber G. Incidence and Current Treatment Gaps in Pediatric Stroke and TIA: An Ontario-Wide Population-Based Study. Neuroepidemiology. 2019;52(3-4):119-127. doi: 10.1159/000493140. Epub 2019 Jan 17. PMID: 30654369.
5)

Garza-Alatorre G, Carrion-Garcia AL, Falcon-Delgado A, Garza-Davila EC, Martinez-Ponce de Leon AR, Botello-Hernandez E. Characteristics of Pediatric Stroke and Association of Delayed Diagnosis with Mortality in a Mexican Tertiary Care Hospital. Neuropediatrics. 2021 Jul 14. doi: 10.1055/s-0041-1731802. Epub ahead of print. PMID: 34261144.

Rosai-Dorfman disease

Rosai-Dorfman disease

Sinus histiocytosis or Rosai-Dorfman disease (RDD) is a rare but well-recognized disorder characterized by an unusual proliferation of histiocytic cells. Intracranial localization is a rare manifestation of RDD.

Rosai-Dorfman disease (RDD) is a rare disease that can be triggered by either viral or bacterial infection. Several parts of the body can be involved, from the CNS to the pelvic regions had been reported.

Conventional MRI, combined with diffusion-weighted imaging and ADC mapping, is an important diagnostic tool in evaluating RDD patients. An accurate diagnosis of RDD should consider the clinical features, imaging characteristics, and the pathological findings 1).


FDG-PET/CT image of a cystic central nervous system Rosai-Dorfman disease 2).

Meningioma.

Rosai-Dorfman disease: especially if extracranial lesions are also identified. Usually in young adults. Isolated intracranial involvement is rare. MRI: duralbased enhancing mass with signal characteristics similar to meningioma, may have dural tail. Most common intracranial locations: cerebral convexities, parasagittal, suprasellar, cavernous sinus. Pathology: dense fibrocollagenous connective tissue with spindle cells and lymphocytic infiltration, stains for CD68 & S-100. Histiocytic proliferation without malignancy. Foamy histiocytes are characteristic. Surgery and immunosuppressive therapy not effective. Low-dose XRT may be the best option.


Some case reports highlights the necessity to consider Rosai-Dorfman disease as a potential posterior fossa tumor differential diagnosis and/or intraventricular tumor.

At present, there is a serious lack of guidelines as to how to treat cases of RDD involving the spine. Current trends show that surgery remains the first method of choice to cure this disease, but in refractory or recurrent RDD, repeat surgery cannot guarantee total resection. Under such circumstances, adjuvant therapy can be very useful.

Rosai-Dorfman disease case reports.


1)

Cheng X, Cheng JL, Gao AK. A Study on Clinical Characteristics and Magnetic Resonance Imaging Manifestations on Systemic Rosai-Dorfman Disease. Chin Med J (Engl). 2018 Feb 20;131(4):440-447. doi: 10.4103/0366-6999.225053. PubMed PMID: 29451149; PubMed Central PMCID: PMC5830829.
2)

Kong Z, Wang Y, Ma W, Cheng X. FDG-PET/CT image of a cystic central nervous system Rosai-Dorfman disease. Eur J Nucl Med Mol Imaging. 2020 Jan 3. doi: 10.1007/s00259-019-04671-3. [Epub ahead of print] PubMed PMID: 31901102.
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