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Jia H, Zhang P, Gu G, Li T, Jiang Z, Wu Z, Wang L, Zhang J, Duan Y, Liu Y, Yang F, Qin S, Zhang L. Brainstem tumors may increase the impairment of behavioral emotional cognition in children. J Neurooncol 2022; 160:423-432. [PMID: 36333568 PMCID: PMC9722802 DOI: 10.1007/s11060-022-04161-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 10/05/2022] [Indexed: 11/06/2022]
Abstract
PURPOSE It remains unclear as to whether patients with brainstem tumor experience complex neuropsychiatric problems. In this cohort study, we specifically investigated behavioral, emotional and cognitive symptoms in pediatric patients with brainstem glioma and healthy individuals. METHODS A total of 146 patients with pediatric brainstem tumors (aged 4-18 years old) and 46 age-matched healthy children were recruited to assess their behaviors and emotions examined by the Child Behavior Checklist. A variety of clinical factors were also analyzed. RESULTS There were significant differences in most behavioral and emotional symptoms between pediatric patients and healthy subjects. Moreover, patients with pons tumors exhibited significantly higher scores than patients with medulla oblongata tumors (p = 0.012), particularly in concerning the syndrome categories of Withdrawn (p = 0.043), Anxious/depressed symptoms (p = 0.046), Thought Problems (p = 0.004), Attention deficits (p = 0.008), Externalizing problems (p = 0.013), and Aggressive behavior (p = 0.004). A tumor body located in the pontine (p = 0.01, OR = 4.5, 95% CI = 1.4-14.059) or DIPG in the midbrain (p = 0.002, OR = 3.818, 95% CI = 1.629-8.948) appears to act as a risk factor that is associated with more problems in patients with neuropsychiatric symptoms. CONCLUSIONS Pediatric patients with brainstem tumors exhibit severe behavioral and emotional problems. Tumor invades the pontine and midbrain act a risk factor with more problems. It suggests that structural and functional abnormalities in the brainstem will cause prolonged behavioral problems and emotional-cognitive dysfunctions in young children.
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Affiliation(s)
- Heyuan Jia
- School of Instrumentation and Optoelectronic Engineering, Beihang University, No.37. BeiHang University XueYuan Road, HaiDian District, Beijing, 100083, China
- Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, BeiHang University XueYuan Road, HaiDian District, BeiJing, 100083, China
| | - Peng Zhang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119. the West Southern 4Th Ring Road, Fengtai District, Beijing, 100073, China
| | - Guocan Gu
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119. the West Southern 4Th Ring Road, Fengtai District, Beijing, 100073, China
| | - Tian Li
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119. the West Southern 4Th Ring Road, Fengtai District, Beijing, 100073, China
| | - Zhuang Jiang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119. the West Southern 4Th Ring Road, Fengtai District, Beijing, 100073, China
| | - Zhen Wu
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119. the West Southern 4Th Ring Road, Fengtai District, Beijing, 100073, China
| | - Liang Wang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119. the West Southern 4Th Ring Road, Fengtai District, Beijing, 100073, China
| | - Junting Zhang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119. the West Southern 4Th Ring Road, Fengtai District, Beijing, 100073, China
| | - Yunyun Duan
- Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, No. 119. the West Southern 4Th Ring Road, Fengtai District, Beijing, 100073, China
| | - Yaou Liu
- Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, No. 119. the West Southern 4Th Ring Road, Fengtai District, Beijing, 100073, China
| | - Feng Yang
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, No. 119. the West Southern 4Th Ring Road, Fengtai District, Beijing, 100073, China.
- Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, 100070, China.
| | - Shaozheng Qin
- State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, No. 19, XinJieKouWai St., HaiDian District, Beijing, 100875, China.
| | - Liwei Zhang
- Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, BeiHang University XueYuan Road, HaiDian District, BeiJing, 100083, China.
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119. the West Southern 4Th Ring Road, Fengtai District, Beijing, 100073, China.
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, No. 119. the West Southern 4Th Ring Road, Fengtai District, Beijing, 100073, China.
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Polli FS, Kohlmeier KA. Prenatal nicotine alters development of the laterodorsal tegmentum: Possible role for attention-deficit/hyperactivity disorder and drug dependence. World J Psychiatry 2022; 12:212-235. [PMID: 35317337 PMCID: PMC8900586 DOI: 10.5498/wjp.v12.i2.212] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 08/07/2021] [Accepted: 01/14/2022] [Indexed: 02/06/2023] Open
Abstract
As we cycle between the states of wakefulness and sleep, a bilateral cholinergic nucleus in the pontine brain stem, the laterodorsal tegmentum (LDT), plays a critical role in controlling salience processing, attention, behavioral arousal, and electrophysiological signatures of the sub- and microstates of sleep. Disorders involving abnormal alterations in behavioral and motivated states, such as drug dependence, likely involve dysfunctions in LDT signaling. In addition, as the LDT exhibits connectivity with the thalamus and mesocortical circuits, as well as receives direct, excitatory input from the prefrontal cortex, a role for the LDT in cognitive symptoms characterizing attention-deficit/hyperactivity disorder (ADHD) including impulsivity, inflexibility, and dysfunctions of attention is suggested. Prenatal nicotine exposure (PNE) is associated with a higher risk for later life development of drug dependence and ADHD, suggesting alteration in development of brain regions involved in these behaviors. PNE has been shown to alter glutamate and cholinergic signaling within the LDT. As glutamate and acetylcholine are major excitatory mediators, these alterations would likely alter excitatory output to target regions in limbic motivational circuits and to thalamic and cortical networks mediating executive control. Further, PNE alters neuronal development and transmission within prefrontal cortex and limbic areas that send input to the LDT, which would compound effects of differential processing within the PNE LDT. When taken together, alterations in signaling in the LDT are likely to play a role in negative behavioral outcomes seen in PNE individuals, including a heightened risk of drug dependence and ADHD behaviors.
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Affiliation(s)
- Filip S Polli
- Drug Design and Pharmacology, University of Copenhagen, Copenhagen 2100, Denmark
| | - Kristi A Kohlmeier
- Drug Design and Pharmacology, University of Copenhagen, Copenhagen 2100, Denmark
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Demirtas-Tatlidede A, Freitas C, Cromer JR, Safar L, Ongur D, Stone WS, Seidman LJ, Schmahmann JD, Pascual-Leone A. Safety and proof of principle study of cerebellar vermal theta burst stimulation in refractory schizophrenia. Schizophr Res 2010; 124:91-100. [PMID: 20817483 PMCID: PMC3268232 DOI: 10.1016/j.schres.2010.08.015] [Citation(s) in RCA: 127] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2010] [Revised: 08/04/2010] [Accepted: 08/09/2010] [Indexed: 12/14/2022]
Abstract
BACKGROUND Early invasive electrical stimulation studies suggested that enhancement of cerebellar vermal activity might prove valuable in symptomatic treatment of refractory neuropsychiatric diseases via modulation of emotion and affect. This proof of principle study aimed to test this hypothesis using noninvasive brain stimulation, and to explore the safety of this protocol in schizophrenia. METHODS Eight treatment-refractory patients with schizophrenia underwent ten sessions of intermittent theta burst stimulation (TBS) to the cerebellar vermis using MRI-guided transcranial magnetic stimulation (TMS). Assessments included side effect questionnaires, cardiovascular monitoring, psychiatric evaluations and comprehensive neuropsychological testing before and after TBS and at one-week follow-up. RESULTS Overall, TBS was tolerated well with mild side effects primarily comprising neck pain and headache. No serious adverse events occurred. Diastolic blood pressure (BP) showed mild decreases for five minutes post-TBS; no significant changes were detected for systolic BP or pulse. PANSS negative subscale showed significant improvements following TBS and during the follow-up. Calgary Depression Scale and self-report visual analog scales for Happiness and Sadness pointed to significant mood elevation. Neuropsychological testing revealed significantly fewer omissions in working memory and interference conditions of a Continuous Performance Test, a longer spatial span and better delay organization on the Rey-Osterrieth Complex Figure during follow-up. No significant worsening in psychiatric or neuropsychological measures was detected. CONCLUSIONS Theta burst stimulation of the cerebellar vermis is safe and well-tolerated, while offering the potential to modulate affect, emotion and cognition in schizophrenia. Future randomized, sham-stimulation controlled studies are warranted to support the clinical efficacy of this technique.
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Affiliation(s)
- Asli Demirtas-Tatlidede
- Harvard Medical School, Boston, MA
- Berenson-Allen Center for Noninvasive Brain Stimulation, Behavioral Neurology Unit, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA
| | - Catarina Freitas
- Harvard Medical School, Boston, MA
- Berenson-Allen Center for Noninvasive Brain Stimulation, Behavioral Neurology Unit, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA
| | - Jennifer R. Cromer
- Harvard Medical School, Boston, MA
- Behavioral Neurology Unit, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA
| | - Laura Safar
- Harvard Medical School, Boston, MA
- Behavioral Neurology Unit, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA
| | - Dost Ongur
- Harvard Medical School, Boston, MA
- Department of Psychiatry, McLean Hospital, Belmont, MA
| | - William S. Stone
- Harvard Medical School, Boston, MA
- Department of Psychiatry, Massachusetts Mental Health Center, Beth Israel Deaconess Medical Center, Boston, MA
| | - Larry J. Seidman
- Harvard Medical School, Boston, MA
- Department of Psychiatry, Massachusetts Mental Health Center, Beth Israel Deaconess Medical Center, Boston, MA
| | - Jeremy D. Schmahmann
- Harvard Medical School, Boston, MA
- Cognitive and Behavioral Neurology Unit, Ataxia Unit, Department of Neurology, Massachusetts General Hospital, Boston, MA
| | - Alvaro Pascual-Leone
- Harvard Medical School, Boston, MA
- Berenson-Allen Center for Noninvasive Brain Stimulation, Behavioral Neurology Unit, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA
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Omar R, Warren JD, Ron MA, Lees AJ, Rossor MN, Kartsounis LD. The neuro-behavioural syndrome of brainstem disease. Neurocase 2007; 13:452-65. [PMID: 18781444 DOI: 10.1080/13554790802001403] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
We describe two patients with isolated brainstem lesions who exhibited behavioural and cognitive changes that are commonly associated with frontal lobe pathology, as leading clinical features. These cases illustrate the role of distributed neural networks in cognitive and behavioural processes. The brainstem, frontal-subcortical and limbic systems are extensively and reciprocally linked via neurotransmitter projection pathways. We argue that cognitive and behavioural features in patients with brainstem lesions reflect remote effects of brainstem structures on frontal lobe and limbic regions, as a consequence of disruption to ascending neurotransmitter pathways.
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Affiliation(s)
- R Omar
- Dementia Research Centre, Institute of Neurology, University College London, Queen Square, London, UK
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Abstract
OBJECTIVE The primary purpose of this article is the presentation of three cases of manic and mixed states associated with an acoustic neuroma, and review of the literature on psychiatric symptoms accompanied by the tumor. METHODS The cases were identified from 830 consecutive inpatient psychiatric admissions over age fifty-five years. Patients were assessed using a Structured Clinical Interview (SCID-R), and met DSM-III-R criteria for the diagnosis of bipolar disorder. The psychopathology seen in acoustic neuroma patients and the pathophysiologic mechanisms proposed to explain them are reviewed. RESULTS The cases we report differ from other cases in the literature in that psychiatric symptoms began pre-operatively and remained for long periods post-operatively. The psychiatric signs and symptoms reported in acoustic neuroma patients are usually described as transient, and these include mood changes, agitation, persecutory delusions, hallucinations, and memory loss and confusional episodes. The disruption of brainstem structures including the auditory pathways, the cerebellum and the ascending reticular system may contribute to mood changes. Systematic studies are necessary to examine their relationship. Although psychological reactions attributable to surgery and facial paralysis may serve as contributory factors the evidence for their role was not striking in the cases we report.
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Affiliation(s)
- B Kalayam
- Cornell University Medical College, White Plains, New York
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Sandyk R, Kay SR, Merriam AE. Atrophy of the cerebellar vermis: relevance to the symptoms of schizophrenia. Int J Neurosci 1991; 57:205-12. [PMID: 1938163 DOI: 10.3109/00207459109150694] [Citation(s) in RCA: 29] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Degeneration of the cerebellar vermis is a common pathological and neuroradiological feature of chronic schizophrenia, but its relationship to symptoms of the disease are poorly understood. We investigated the relationship of vermal cerebellar atrophy on CT scan to features of positive (productive) and negative (defect) dimensions of schizophrenia as well as to symptoms of general psychopathology in a sample of 23 chronic schizophrenic patients. For comparison, we also studied the relationship of third ventricular width (TVW), which reflects periventricular and diencephalic atrophy, to these features of schizophrenic symptomatology. Vermal cerebellar atrophy was found in 43.5% of patients and correlated significantly with general psychopathology and, more specifically, with feelings of guilt and disturbance of volition. It was unrelated to global positive or negative features of schizophrenia. By contrast, TVW was uniquely associated with global negative syndrome. These observations indicate that degeneration of the cerebellar vermis and enlargement of the third ventricle are integral aspects of schizophrenia, and that each contributes independently to specific clinical aspects of the disease.
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Affiliation(s)
- R Sandyk
- Department of Psychiatry, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York, NY 10461
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