Medulloblastomas, CNS embryonal tumors, and cerebellar mutism syndrome: advances in care and future directions.

Central nervous system (CNS) embryonal tumors, commonly found in pediatric patients, represent a heterogeneous mix of lesions with an overall poor (though improving) prognosis. Medulloblastomas are by far the most frequently encountered and most widely studied subtype, though others include atypical teratoid/rhabdoid tumors (AT/RTs), embryonal tumor with multilayered rosettes (ETMRs), and CNS neuroblastomas, FOX-R2 activated. The classification, diagnosis, and treatment of these lesions have evolved drastically over the years as their molecular underpinnings have been elucidated. We describe the most recent 2021 WHO Classification system, discuss current understanding of the genetic basis, and demonstrate current thinking in treatment for these highly complex tumors. Since surgical resection continues to remain a mainstay of treatment, preventing and managing surgical complications, especially cerebellar mutism syndrome (CMS), is paramount. We describe the current theories for the etiology of CMS and two centers' experience in mitigating its risks. As our surgical toolbox continues to evolve along with our understanding of these tumors, we hope future patients can benefit from both improved overall survival and quality of life.

Cerebellar Mutism Syndrome in Pediatric Neuro-oncology: A Multidisciplinary Perspective and Call for Research Priorities.

Cerebellar mutism syndrome (CMS), also known as posterior fossa syndrome, occurs in a subset of children after posterior fossa tumor resection, most commonly medulloblastoma. Patients with this syndrome exhibit often transient, although protracted, symptoms of language impairment, emotional lability, cerebellar, and brainstem dysfunction. However, many patients experience persistent neurological deficits and lasting neurocognitive impairment. Historically, research and clinical care were hindered by inconsistent nomenclature, poorly defined diagnostic criteria, and uncertainty surrounding risk factors and etiology. Proposed diagnostic criteria include two major symptoms, language impairment and emotional lability, as proposed by the international Board of the Posterior Fossa Society in their consensus statement as well as other experts in this field. Risk factors most commonly associated with development of CMS include midline tumor location, diagnosis of medulloblastoma and specific tumor subtype, younger age at diagnosis, and preoperative language impairment. A proposed etiology of CMS includes disruption of the cerebellar outflow tracts, the cerebellar nuclei, and their efferent projections through the superior cerebellar peduncle. Treatment for CMS remains supportive. Herein, we present a comprehensive overview of CMS etiology, diagnosis, risk factors, clinical presentation, and clinical management. In addition, we identify essential multidisciplinary research priorities to advance diagnostics, prevention, and intervention efforts for patients with, or at risk for, development of CMS.

Efectividad del tratamiento temprano de niños con mutismo selectivo en los centros educativos / Effectiveness of early treatment of children with selective mutism in educational centers

Resumen El mutismo selectivo (MS) es un trastorno de ansiedad de baja prevalencia, lo que dificulta su investigación. Pese a su inicio temprano su diagnóstico no suele hacerse antes del acceso a la escolaridad obligatoria. El objetivo de este estudio fue valorar la eficiencia de un protocolo cognitivo-conductual para la intervención psicológica en el contexto educativo (ipmsce), siguiendo los criterios de la Task Force in Promotion and Dissemination of Psychological Procedures. Participaron 10 niños que presentaban una demora inferior a dos años entre el inicio del MS y su diagnóstico (1.00 ± 0.54). La edad media fue de 4.94 años y el 80% fueron niñas. Se utilizó un diseño de acumulación de casos, con medidas del tratamiento antes de su aplicación, al finalizar y en un seguimiento a los 12 meses, obtenidas a través de los padres, los profesores y un test situacional. Los resultados muestran la efectividad de la intervención.

Abstract Selective mutism (SM) is an anxiety disorder of low prevalence, which makes its investigation difficult. Despite its early start, its diagnosis is not usually made before access to compulsory schooling. The objective of this study was to assess the efficiency of a cognitive-behavioral protocol for psychological intervention in the educational context (ipmsce), following the criteria of the Task Force in Promotion and Dissemination of Psychological Procedures. Ten children with a delay of less than two years between the onset of SM and its diagnosis (1.00 ± 0.54) participated. The average age was 4.94 years and 80 % were girls. A case accumulation design was used, with measures of treatment before its application, at the end and in a followup at 12 months, obtained through parents, teachers and a situational test. The results show the effectiveness of the intervention.

The multiple faces of catatonia in autism spectrum disorders: descriptive clinical experience of 22 patients over 12 years.

A retrospective review was conducted from the inpatient and outpatient records of twenty-two autistic youth presenting to a neurobehavioral service over a twelve-year period for combined psychiatric and behavioral pathology who also met DSM5 criteria for catatonia. Six autistic girls and 16 autistic boys ranging from ages eight to 26 years old were identified, and their variegated symptoms evaluated. Stereotypy, posturing, negativism, mutism and stupor were the most common catatonic symptoms, each present in more than half of the study patients. One patient had abnormal vital signs indicative of malignant catatonia. Twenty patients had concomitant repetitive self-injurious behaviors that had led to significant tissue injury and were refractory to psychotropic and behavioral interventions. The sample was weighted towards patients with severe self-injurious behavior, which often was the reason for admission. The many "faces" of catatonia in autism spectrum disorders are seen in this sample, and the novel recognition of repetitive self-injury as an under-recognized motor symptom of catatonia is highlighted. The preliminary findings in this study open many important future vistas for ongoing research regarding catatonia in ASDs.

Mutismo Selectivo: Revisión de la literatura / Selective Mutism: a review

El mutismo selectivo es un cuadro clínico caracterizado por una falta constante del habla en situaciones sociales específicas en las que hay una expectativa de hablar, a pesar de hacerlo en otras situaciones. El objetivo del presente trabajo es realizar una revisión narrativa de la evidencia en relación a este trastorno, con un énfasis en la evolución que presentan estos pacientes. La evidencia muestra que, si bien los síntomas generalmente mejoran con el tiempo, las personas a menudo continúan exhibiendo problemas de comunicación, un peor desempeño académico y laboral, además de presentar un mayor riesgo de otros trastornos psiquiátricos, principalmente Trastorno de Ansiedad Social. Es necesaria mayor investigación respecto al seguimiento de estos pacientes considerando la escasa evidencia disponible y el gran impacto que genera en el paciente y su familia.

Abstract. Selective mutism is a disorder in which an individual fails to speak in certain social situations, in spite of being able to speak normally in other settings. The aim of the present work is to perform a narrative review of the evidence in relation to this disorder, with an emphasis on the progression presented by these patients. Evidence shows that, although symptoms generally improve over time, people often continue to exhibit communication problems, have a worse academic and work performance than expected, and present a higher risk of other psychiatric disorders, mainly Social Anxiety Disorder. Further research is necessary regarding the follow-up of these patients, considering the limited available evidence and the great impact it has on the patient and his family.

The Use of Lorazepam and Electroconvulsive Therapy in the Treatment of Catatonia: Treatment Characteristics and Outcomes in 60 Patients.

OBJECTIVES: Lorazepam and electroconvulsive therapy (ECT) are effective treatments for catatonia. However, systematic data on these treatments in catatonia are limited. In the present study, we aimed to investigate the clinical and treatment-related characteristics of patients with catatonia who underwent lorazepam and/or ECT. METHODS: Between January 2012 and December 2016, we received 60 patients with catatonia hospitalized in the Gaziantep University Faculty of Medicine Clinic of Psychiatry. Lorazepam and/or ECT were used in the patients' treatment schedule. Treatment results were evaluated using the Bush-Francis Catatonia Rating Scale and Clinical Global Impression-Improvement. RESULTS: Thirty-five patients (58.3%) in the sample were in their first catatonic episode. The most common comorbidity was mood disorder (n = 34, 56.7%), whereas the most frequent catatonic sign was mutism (n = 43, 71.7%). Moreover, 31 patients (51.7%) had some form of medical comorbidity. Cerebral abnormalities were detected in computed tomography/magnetic resonance imaging in 22 patients (36.7%). Furthermore, 95% of the patients (n = 57) fully recovered after administration of the treatment. CONCLUSIONS: Lorazepam is a reasonable initial choice in the treatment of catatonia, with rapid consideration for ECT if there is no rapid response to lorazepam.

Cerebellar mutism.

INTRODUCTION: Cerebellar mutism (CM) is defined as a peculiar form of mutism that may complicate the surgical excision of posterior cranial fossa tumor. The incidence is variable in the literature, occurring in up to one third of cases in some series. Commonly occurring peculiar features of CM are delayed onset following surgery, limited duration, and spontaneous recovery usually associated with dysarthria. METHODS: A review has been performed concerning anatomical substrates and circuits actually considered to be involved in the development of cerebellar mutism, as well as risk factors for its development that have been documented in the literature. Attention has also been given to the long-term prognosis and the possibilities of rehabilitation that can be considered in these children, which has been compared with the authors' institutional experience. RESULTS AND CONCLUSIONS: Tumor infiltration of the brainstem seems to represent the most relevant feature related to the development of CM, along with the histological diagnosis of medulloblastoma. On the other hand, hydrocephalus does not represent an independent risk factor. The higher rate of CM in children seems to be related to the higher incidence in children of tumors with malignant histology and brain stem involvement. Surgical technique does not seem to have a definite role; in particular, the use of a telovelar approach as compared to vermian split to reach the fourth ventricle extension of the tumor has not been demonstrated to prevent the development of cerebellar mutism. Concerning long-term prognosis, around one third of the children who develop cerebellar mutism after surgery have a persistent dysarthria, the remaining ones showing a residual phonological impairment. Long-term dysarthric features tend to be more severe and less prone to recovery in children presenting at diagnosis with associated combined procedural memory and defective neurocognitive functions.

Cause and outcome of cerebellar mutism: evidence from a systematic review.

PURPOSE: Cerebellar mutism is a serious neurosurgical complication after posterior fossa surgery, but the cause, incidence and outcome remain incompletely defined. The aim of this paper was to identify and review all reports of this phenomenon to better delineate and improve the evidence base. METHODS: A systematic search and retrieval of databases was conducted using advanced search techniques. Review/outcomes criteria were developed, and study quality was determined. RESULTS: The retrieval identified 2,281 papers of which 96 were relevant, identifying 650 children with cerebellar mutism. Causative factors, clinical features and outcomes were reported variably; papers focussed on multiple areas, the majority reporting incidence in single or series of case studies with little or no analysis further than description. CONCLUSIONS: The complexity and variability of data reporting, likely contributing factors and outcomes make cerebellar mutism difficult to predict in incidence and the degree of impact that may ensue. A clear and accepted universal definition would help improve reporting, as would the application of agreed outcome measures. Clear and consistent reporting of surgical technique remains absent. Recommendations for practice are provided.

Cerebellar mutism.

Mutism of cerebellar origin is a well-described clinical entity that complicates operations for posterior fossa tumors, especially in children. This review focuses on the current understanding of principal pathophysiological aspects and risk factors, epidemiology, clinical characteristics, treatment strategies, and outcome considerations. The PubMed database was searched using the term cerebellar mutism and relevant definitions to identify publications in the English-language literature. Pertinent publications were selected from the reference lists of the previously identified articles. Over the last few years an increasing number of prospective studies and reviews have provided valuable information regarding the cerebellar mutism syndrome. Importantly, the clarification of principal terminology that surrounds the wide clinical spectrum of the syndrome results in more focused research and more effective identification of this entity. In children who undergo surgery for medulloblastoma the incidence of cerebellar mutism syndrome was reported to be 24%, and significant risk factors so far are brainstem involvement and midline location of the tumor. The dentate-thalamo-cortical tracts and lesions that affect their integrity are considered significant pathophysiological issues, especially the tract that originates in the right cerebellar hemisphere. Moderate and severe forms of the cerebellar mutism syndrome are the most frequent types during the initial presentation, and the overall neurocognitive outcome is not as favorable as thought in the earlier publications. Advanced neuroimaging techniques could contribute to identification of high-risk patients preoperatively and allow for more effective surgical planning that should focus on maximal tumor resection with minimal risk to important neural structures. Properly designed multicenter trials are needed to provide stronger evidence regarding effective prevention of cerebellar mutism and the best therapeutic approaches for such patients with a combination of pharmacological agents and multidisciplinary speech and behavior augmentation.

A case of selective mutism in an 8-year-old girl with thalassaemia major after bone marrow transplantation.

Selective mutism is rare with a prevalence below 1% in the general population, but a higher prevalence in populations at risk (children with speech retardation, migration). Evidence for treatment strategies is hardly available. This case report provides information on the treatment of selective mutism in an 8-year-old girl with preexisting thalassaemia major. As medications she received penicillin prophylaxis (500000 IE/d) and deferasirox (Exjade; 20-25mg/kg/d), an iron chelator. The preexisting somatic disease and treatment complicated the treatment, as there are no data about pharmacological combination therapy. Psychotherapy in day treatment, supported by the use of the SSRI fluoxetine (10 mg), led to a decrease in the selective mutism score from 33 to 12 points, GAF improved by 21 points. Mean levels of fluoxetine plus norfluoxetine were 287.8 ng/ml without significant level fluctuations.

[Hysterical mutism]. / Le mutisme hystérique.

BACKGROUND: Conversion disorders comprise many clinical pictures, including hysterical mutism. Hysterical mutism has emerged as a clinical entity that remains difficult to diagnose, and whose treatment is poorly codified. Hysterical mutism is a disorder of the vocal function without changing the integrity of the body, resulting in loss of voice. Identified at all times, hysterical mutism entered the medical field in the late nineteenth century, under the direction of Jean-Martin Charcot (Salpêtrière School). Since then, although the disorder has emerged as a clinical entity, it remains little known. METHOD: A systematic review of the literature. We performed electronic literatures search of relevant studies using Medline, SUDOC, and BIUM. Search terms used were mutism, functional aphonia, conversion disorder, hysteria. RESULTS: The epidemiology of hysterical mutism is difficult to assess. The first limitation is the lack of consensensual diagnostic criteria. An estimate of its frequency may be advanced through registries consultation of otolaryngology-head and neck surgery. Through a literature review, emerges a rare disorder, about 5% of functional dysphonia. The sex-ratio is in favour of women. Regarding age of onset of disorder, functional aphonia mainly concerns adults with an average around the age of 30-40 years. The onset of the disorder typically involves a sudden onset and a recent stressful event. The duration of the disorder is difficult to specify. It appears that this dysfunction is rapidly reversible and that the majority of patients are in remission of this disorder within three months. The recurrence of dysfunction seems to be frequent. The existence of psychiatric comorbidity did not appear to be the rule. The natural history of this disorder is not known making it tricky to evaluate the efficiency of therapeutic approaches. CONCLUSION: Today the term hysterical mutism does not appear as an entity in either international classification. It belongs to the category of conversion disorder in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). Identified as a medical entity described by the school of the Salpêtrière, this disorder has raised little interest. The medicalization of the condition remains difficult because of the importance of stigma associated with it, which contributes to the rejection rather than support of patients with mutism. To better understand this disorder and improve the care of patients who suffer, renewed interest is warranted.

Postoperative cerebellar mutism and autistic spectrum disorder.

PURPOSE: I read the article "An Inside View of Autism" written by a 44-year-old autistic woman who had a successful international career designing livestock equipment. In this article, she wrote about her life, disease, and experiences as an autistic individual. She stated that "It is interesting that my speech resembled the stressed speech in young children who have had tumors removed from the cerebellum". METHODS: In this article, we intend to review and extensively document both postoperative cerebellar mutism and autistic spectrum disorder. RESULTS: We reviewed the clinical and neurological findings, etio-pathogenesis, neuroanatomy, mechanisms of development, and similarities between the etio-pathogenesis of both diseases. CONCLUSIONS: Cerebellar lesions can produce mutism and dysarthria, symptoms sometimes seen in autistic spectrum disorder. In mammals, cerebellar lesions disturb motivated behavior and reduce social interactions, functions that are disturbed in autistic spectrum disorder and cerebellar mutism. The cerebellum and two regions within the frontal lobes are active in certain language tasks. Language is abnormal in autistic spectrum disorder and cerebellar mutism.

Tratamiento multicomponente de un caso de mutismo selectivo / Multicomponent treatment in a case of selective mutism

Este trabajo presenta el proceso de evaluación y tratamiento de una niña de 6 años que cumple con los criterios para el diagnóstico del mutismo selectivo (APA, 2002). La intervención se realizó utilizando estrategias que incluyen el ámbito individual y el contexto institucional (familia y escuela). Con el fin de alcanzar los objetivos terapéuticos propuestos se diseñaron dos fases diferenciadas en la intervención. La primera incluyó la transmisión de información a padres y personal del centro educativo, así como la instrucción y modelado de los comportamientos deseables y no deseables respecto del problema de la niña; la segunda consistió en el tratamiento de la inhibición del habla mediante desvanecimiento estimular, instigación verbal, refuerzo positivo, economía de fichas y exposición simbólica gradual y trucada. Los resultados mostraron que el habla espontánea en clase, así como el habla y la participación en el juego, se normalizaron y mantuvieron en las medidas de seguimiento a corto, medio y largo plazo.

[Mutism in children]. / Mutismo en niños.

INTRODUCTION: Mutism is absence of verbal expression with conservation of language comprehension. The origin of mutism is multifactorial and may followed from cranial trauma surgery of the posterior fossa, acquired epileptic syndromes and psychogenic origin. OBJECTIVE: To refer patients who had presented mutism of diverse etiology. CLINICAL CASES: We analysed three children who had presented mutism originated by diverse causes. Case 1. A child with family and school problems, attention deficits and limited communication resources. Neurological examination and other auxiliary test (EEG) were normal. He presented no alteration in language or speech. We recommended the change of the school and a psychotherapeutic orientation. Case 2. A 4 year old female child who has suffered varicella 15 days earlier and presented limitations in her verbal expression despite maintain her linguistically capacity. She showed a indifferent behavior and her movements were without finality. Neurological examination was normal. The girl understood and followed instruction properly. However her verbal communication was absent. Total recuperation occurred in 72 hours. Case 3. A 12 years old child who had suffered a cranial traumatism with loss of consciousness ten days earlier. After this traumatism, he presented behavior changes, disorientation and blurred vision. Additionally he presented stereotypies and limitations in psychosocial connections. Despite his mutism, he conserved the structure and content of language. SPECT showed hypoperfusion in orbitotemporal region. Improvement was total 20 days after his traumatism. CONCLUSIONS: The mutism has multifactorial etiology. References were made to three cases who's mutism was related to emotional causes, post-varicella complications and posttraumatic events.

Mutism: elective or selective, and acquired.

When a child does not speak, this may be because there is no wish to do so (elective or selective mutism), or the result of lesions in the brain, particularly in the posterior fossa. The characteristics of the former children are described, especially their shyness; and it is emphasized that mild forms are quite common and a definitive diagnosis should only be made if the condition is significantly affecting the child and family. In the case of mutism due to organic causes, the commonest of these is trauma to the cerebellum. Operations on the cerebellum to remove tumours can be followed by mutism, often after an interval of a few days, and it may last for several months or longer, to be followed by dysarthria. Other rarer causes are discussed, and also the differential diagnosis. The so-called posterior fossa syndrome consists of mutism combined with ataxia, cranial nerve palsies, bulbar palsies, hemiparesis, cognitive impairment and emotional lability, but the post-operative symptoms are often dominated by the lack of speech. The most accepted cause for the condition is vascular spasm with involvement of the dentate nucleus and the dentatorubrothalamic tracts to the brain-stem, and subsequently to the cortex. Diaschisis may be involved in causing the loss of higher cerebral functions, and possibly, complicating hydrocephalus. The treatment of elective mutism is reviewed, either using a psychotherapeutic approach or a variety of drugs, or both. These may well be ineffective, and it must be remembered that the condition often resolves on its own. The former treatment must concentrate on the training of social skills and activities of daily life and must be targeted to both the child, the family, and the school. Also, all kinds of punishment and insistence on speech must be discouraged. The drug, which seems to be most effective, is fluoxetine. Discovering more about the causes of mutism due to organic causes may well depend on studies using such techniques as magnetic resonance imaging and single photon emission tomography.