Medical management for cerebellar mutism syndrome following posterior fossa surgery: A systematic review.

INTRODUCTION: Cerebellar mutism syndrome (CMS) is a serious complication of posterior fossa surgeries affecting mainly pediatric age group. The pathophysiology is still not fully understood. It adversely affects the recovery of patients. There is no definitive and standardized management for CMS. However pharmacological therapy has been used in reported cases with variable effectiveness. We aim through this review to summarize the available evidence on pharmacological agents used to treat CMS. METHOD: A thorough systematic review until December 2022, was conducted using PubMed Central, Embase, and Web of Science, databases to identify case reports and case series of CMS patients who underwent posterior fossa surgery and received pharmacological treatment. Patients with pathologies other than posterior fossa lesions were excluded from the study. RESULTS: Of 592 initial studies, 8 studies met our eligibility criteria for inclusion, with 3 more studies were added through manual search; reporting on 13 patients. The median age of 13 years (Standard deviation SD=10.60). The most frequent agent used was Bromocriptine. Other agents were fluoxetine, midazolam, zolpidem, and arpiprazole. Most patients recovered within 48 hours of initiating medical therapy. The median follow-up period was 4 months (SD=13.8). All patients showed complete recovery at the end of follow-up period. CONCLUSION: Cerebellar mutism syndrome is reported after posterior fossa surgeries, despite attempts to identify risk factors, pathophysiology, and management of CMS, it remains a challenging condition with significant morbidity. Different Pharmacological treatments have been proposed with promising results. Further studies and formalized clinical trials are needed to evaluate available options and their effectiveness.

Cerebellar Mutism Syndrome and Dentato-Thalamo-Cortical Tract Disruption in Diffusion Tractography Following Surgery for Medulloblastoma.

Background Cerebellar mutism syndrome (CMS), a complication following medulloblastoma surgery, has been linked to dentato-thalamo-cortical tract (DTCT) injury; the association of the degree of DTCT injury with severity of CMS-related symptoms has not been investigated. Purpose To investigate the association between severity of CMS-related symptoms and degree and patterns of DTCT injury with use of diffusion tensor imaging (DTI), and if laterality of injury influences neurologic symptoms. Materials and Methods This retrospective case-control study used prospectively collected clinical and DTI data on patients with medulloblastoma enrolled in a clinical trial (between July 2016 and February 2020) and healthy controls (between April and November 2017), matched with the age range of the participants with medulloblastoma. CMS was divided into types 1 (CMS1) and 2 (CMS2). Multivariable logistic regression was used to investigate the relationship between CMS likelihood and DTCT injury. Results Overall, 82 participants with medulloblastoma (mean age, 11.0 years ± 5.2 [SD]; 53 male) and 35 healthy controls (mean age, 18.0 years ± 3.06; 18 female) were included. In participants with medulloblastoma, DTCT was absent bilaterally (AB), absent on the right side (AR), absent on the left side (AL), or present bilaterally (PB), while it was PB in all healthy controls. Odds of having CMS were associated with higher degree of DTCT damage (AB, odds ratio = 272.7 [95% CI: 269.68, 275.75; P < .001]; AR, odds ratio = 14.40 [95% CI: 2.84, 101.48; P < .001]; and AL, odds ratio = 8.55 [95% CI: 1.15, 74.14; P < .001). Left (coefficient = -0.07, χ2 = 12.4, P < .001) and right (coefficient = -0.15, χ2 = 33.82, P < .001) DTCT volumes were negatively associated with the odds of CMS. More participants with medulloblastoma with AB showed CMS1; unilateral DTCT absence prevailed in CMS2. Lower DTCT volumes correlated with more severe ataxia. Unilateral DTCT injury caused ipsilateral dysmetria; AB caused symmetric dysmetria. PB indicated better neurologic outcome. Conclusion The severity of CMS-associated mutism, ataxia, and dysmetria was associated with DTCT damage severity. DTCT damage patterns differed between CMS1 and CMS2. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Dorigatti Soldatelli and Ertl-Wagner in this issue.

Proceedings of the first global meeting of the Posterior Fossa Society: state of the art in cerebellar mutism syndrome.

PURPOSE: The Posterior Fossa Society, an international multidisciplinary group, hosted its first global meeting designed to share the current state of the evidence across the multidisciplinary elements of pediatric post-operative cerebellar mutism syndrome (pCMS). The agenda included keynote talks from world-leading speakers, compelling abstract presentations and engaging discussions led by members of the PFS special interest groups. METHODS: This paper is a synopsis of the first global meeting, a 3-day program held in Liverpool, England, UK, in September 2022. RESULTS: Topics included nosology, patient and family experience, cerebellar modulation of cognition, and cerebellar cognitive affective syndrome. In addition, updates from large-scale studies were shared as well as abstracts across neuroradiology, neurosurgery, diagnosis/scoring, ataxia, and rehabilitation. CONCLUSIONS: Based on data-driven evidence and discussions, each special interest group created research priorities to target before the second global meeting, in the spring of 2024.

Catatonia associated with pediatric postoperative cerebellar mutism syndrome.

OBJECTIVE: To ascertain the presence of catatonia in cases of pediatric postoperative cerebellar mutism syndrome (PPCMS). METHOD: A systematic review of PPCMS case reports of patients aged 0-17 years with sufficient clinical information to extract catatonic phenomena was undertaken following PRISMA guidelines. Standardized catatonia rating scales were applied to selected cases retrospectively to ascertain whether diagnostic criteria for catatonia were met. A case known to the authors is also presented. RESULTS: Two hundred twenty-one suitable full-text articles were identified. Following screening and application of inclusion criteria, 51 articles were selected plus seven more from their references, reporting on 119 subjects. All cases met Bush and Francis (BF) diagnostic criteria for catatonia, 92.5% Pediatric Catatonia Rating Scale (PCRS), 52.9% ICD-11, and 44.5% DSM-5. All patients presented with mutism. The next most frequent signs were immobility/stupor (77.3%), withdrawal (35.3%), mannerisms (23.5%), and excitement/agitation (18.5%). Most cases presented with stuporous catatonia (75.6%). Catatonia most frequently occurred following resection of medulloblastoma (64.7%). Preoperative hydrocephalus occurred in 89 patients (74.8%). CONCLUSION: Catatonia was frequent in this PPCMS sample, with a predominant stuporous variant; it should be considered in patients with PPCMS and assessed with reliable and validated instruments for prompt diagnosis and management.

Adaptive, behavioral, and emotional outcomes following postoperative pediatric cerebellar mutism syndrome in survivors treated for medulloblastoma.

OBJECTIVE: Patients who experience postoperative pediatric cerebellar mutism syndrome (CMS) during treatment for medulloblastoma have long-term deficits in neurocognitive functioning; however, the consequences on functional or adaptive outcomes are unknown. The purpose of the present study was to compare adaptive, behavioral, and emotional functioning between survivors with and those without a history of CMS. METHODS: The authors examined outcomes in 45 survivors (15 with CMS and 30 without CMS). Comprehensive neuropsychological evaluations, which included parent-report measures of adaptive, behavioral, and emotional functioning, were completed at a median of 2.90 years following craniospinal irradiation. RESULTS: Adaptive functioning was significantly worse in the CMS group for practical and general adaptive skills compared with the group without CMS. Rates of impairment in practical, conceptual, and general adaptive skills in the CMS group exceeded expected rates in the general population. Despite having lower overall intellectual functioning, working memory, and processing speed, IQ and related cognitive processes were uncorrelated with adaptive outcomes in the CMS group. No significant group differences or increased rates of impairment were observed for behavioral and emotional outcomes. CONCLUSIONS: Survivors with CMS, compared with those without CMS, are rated as having significant deficits in overall or general adaptive functioning, with specific weakness in practical skills several years posttreatment. Findings from this study demonstrate the high risk for ongoing functional deficits despite acute recovery from symptoms of CMS, highlighting the need for intervention to mitigate such risk.

[Neuroleptic Intolerance and Residual Mutism in a Young Woman with Anti-N-Methyl-D-Aspartate Receptor (NMDAR) Encephalitis].

We report a case of anti-NMDAR encephalitis and residual mutism in a 23-year-old woman who presented with neuroleptic intolerance. Admission to our department for investigation of her abnormal behavior revealed cerebrospinal fluid (CSF) positivity for anti-NMDAR antibodies, and the patient underwent immunotherapy. However, generalized tonic seizures developed, requiring mechanical ventilation in the intensive care unit. Antipsychotic drugs were also administered for involuntary movements and insomnia. Thereafter, a malignant syndrome of severe hyperCKemia (Max: 191,120 IU/L) and shock developed, requiring resuscitation and three sessions of hemodialysis. Subsequent rituximab therapy led to improvement, except for mutism, which had newly developed during resuscitation. Seven months after initial admission, the patient was discharged with independent gait. However, her mutism still persists. Temporary mutism has been reported to occur in this type of encephalitis, albeit rarely. The fact that remission was not observed in this case may have been due to cerebellar infarction occurring during resuscitation, but the true cause remains unclear. Malignant syndrome or rhabdomyolysis, as seen in this patient, has also sometimes been reported in this form of encephalitis when antipsychotic agents, especially dopamine receptor blockers, have been administered. Therefore, such agents should be administered with caution in patients with anti-NMDAR encephalitis. (Received August 17, 2023; Accepted October 24, 2023; Published March 1, 2024).

Vestibular Testing and Impairments in Postoperative Pediatric Cerebellar Mutism Syndrome: A Case Series.

BACKGROUND: Postoperative pediatric cerebellar mutism syndrome (CMS) may occur following a process affecting the posterior cranial fossa. Recent evidence demonstrates disabling and potentially lasting motor components of this syndrome, including ataxia, hemiparesis, and oculomotor dysfunction. These impairments may contribute to vestibular deficits. METHODS: This case series contributes data to quantify vestibular dysfunction in postoperative CMS. The pair consisted of one female and one male. RESULTS: Vestibular testing demonstrated both peripheral and central dysfunction. CONCLUSIONS: Given these findings, a thorough vestibular assessment may be indicated as part of a comprehensive evaluation following a postoperative CMS diagnosis. Further research is needed to understand the pathophysiology, treatment, and long-term outcomes of postoperative pediatric CMS.

Evaluation of safety of fluoxetine for cerebellar mutism syndrome in children after posterior fossa surgery.

BACKGROUND: Cerebellar mutism syndrome (CMS) occurs in 8-29 % of children undergoing posterior fossa tumor surgery. Its main symptoms are mutism and emotional lability. Although it is always transient, recovery time can be lengthy with long-term cognitive sequelae. There is no approved drug treatment for CMS, but some drugs are used in everyday medical practice. One of these is fluoxetine, which has been used for many years in our institution. The main objective of this study was to establish the safety profile of fluoxetine in this condition. MATERIALS AND METHODS: The records of patients admitted to the pediatric intensive care unit after brain surgery at Angers University Hospital from 2010 to 2020 were reviewed. Children aged 2 years and older who underwent a posterior fossa tumor surgery and were diagnosed with CMS were included. Data on patient characteristics, prescription of fluoxetine treatment, side effects if any, and complete mutism duration were collected. RESULTS: Among 246 patients admitted to the pediatric intensive care unit for brain surgery during the study period, 23 had CMS and eight were prescribed fluoxetine. No serious adverse event related to fluoxetine was reported. Complete mutism duration did not differ significantly between the fluoxetine group and the non-fluoxetine group(p = 0.22). However, the treatment was initiated after recovery from complete mutism in half of the treated patients. CONCLUSION: This study suggests a positive safety profile of fluoxetine used in postoperative CMS. It does not answer the question of whether the treatment is effective for this indication. A randomized controlled trial based on a syndrome severity scale should be conducted to provide a more reliable assessment of the efficacy and safety of fluoxetine.

REhabilitation Approaches in CHildren with cerebellar mutism syndrome (REACH): An international cross-disciplinary survey study.

OBJECTIVE: Pediatric cerebellar mutism syndrome (pCMS) can occur following resection of a posterior fossa tumor and, although some symptoms are transient, many result in long-lasting neurological deficits. A multi-disciplinary rehabilitation approach is often used in cases of pCMS; however, there have been no clinical trials to determine gold standards in rehabilitation practice in this population, which remains a research priority. The purpose of this study was to identify and compare intervention practices used in pCMS throughout the disciplines of occupational and physical therapy, speech-language pathology, and neuropsychology across geographic regions. METHODS: A 55-question e-survey was created by an international multidisciplinary research group made up of members of the Posterior Fossa Society and sent to rehabilitation professionals in pediatric neuro-oncology centers in the US, Canada, and Europe. RESULTS: Although some differences in the type of intervention used in pCMS were identified within each discipline, many of the targeted interventions including dose, frequency, and intensity were similar within disciplines across geographic regions. In addition, there were common themes identified across disciplines regarding challenges in the rehabilitation of this population. CONCLUSION: These results provide a foundation of current practices on which to build future intervention-based clinical trials.

Atypical neuroleptic malignant syndrome in an incarcerated patient: a demographic who may be at increased risk.

An incarcerated male patient with a psychiatric history of schizoaffective disorder presented to the emergency department with muscle rigidity and mutism after receiving a 150 mg haloperidol decanoate injection. At the peak of his illness, symptoms included muscular rigidity, mutism, excessive drooling, an altered level of consciousness, tachycardia, diaphoresis and tremors. Atypical neuroleptic malignant syndrome (NMS) was diagnosed after discrediting similar illnesses through clinical reasoning, laboratory and imaging studies. He was successfully treated during a 40-day hospitalisation with lorazepam, amantadine, methocarbamol and supportive care. This case represents an atypical presentation of NMS due to the patient's lack of fever development. Nonetheless, he satisfied many other criteria, most notably rapid symptom onset after receiving a first-generation antipsychotic medication. The case also provides an opportunity to discuss the prevalence of psychiatric illness among the US incarcerated population and incarceration as a risk factor for developing NMS.

Phasic Versus Tonic Irritability and Associations with Family Accommodation Among Youth with Selective Mutism: A Latent Profile Analysis.

Clinical presentations of selective mutism (SM) vary widely across affected youth. Although studies have explored general externalizing problems in youth with SM, research has not specifically examined patterns of irritability. Relatedly, research has not considered how affected families differentially accommodate the anxiety of youth with SM as a function of the child's temper outbursts (i.e., phasic irritability) and general angry mood (i.e., tonic irritability). Data were drawn from a sample of treatment-seeking children and adolescents with a primary diagnosis of selective mutism (N = 152; Mean age = 6.12 years; 67.11% female), and their caregivers. Latent profile analysis (LPA) was used to identify distinct profiles in SM youth that were characterized by varying levels of phasic and/or tonic irritability. Analyses further examined whether these different profiles were associated with different levels of family accommodation and global impairment. LPA identified 5 profiles: SM with No irritability, SM with Low Phasic Irritability, SM with High Phasic Irritability, SM with High Phasic and Moderate Tonic Irritability, and SM with High Phasic and High Tonic Irritability. Patterns of family accommodation and global impairment were highest among youth belonging to profiles characterized by high phasic irritability. Findings highlight separable patterns of irritability across youth with SM, with phasic irritability (i.e., temper outbursts) appearing particularly linked with increased family accommodation and overall global impairment. Assessing phasic irritability is critical for optimizing treatment in youth with SM and can be useful for flagging possible patterns of family accommodation contributing to overall impairment.

National multicentered retrospective review of clinical and intraoperative factors associated with the development of cerebellar mutism after pediatric posterior fossa tumor resection.

BACKGROUND: Cerebellar mutism (CM) is characterized by a significant loss of speech in children following posterior fossa (PF) surgery. The biological origin of CM remains unclear and is the subject of ongoing debate. Significant recovery from CM is less likely than previously described despite rigorous multidisciplinary neuro-rehabilitational efforts. METHODS: A national multi-centered retrospective review of all children undergoing PF resection in four midsized Canadian academic pediatric institutions was undertaken. Patient, tumor and surgical factors associated with the post-operative development of CM were reviewed. Retrospective identification of PF surgery patients including those developing and those that did not (internal control). RESULTS: The study identified 258 patients across the 4 centers between 2010 and 2020 (mean age 6.73 years; 42.2% female). Overall, CM was experienced in 19.5% of patients (N = 50). Amongst children who developed CM histopathology included medulloblastoma (35.7%), pilocytic astrocytoma (32.6%) and ependymoma (17.1%). Intraoperative impression of adherence to the floor of the 4th ventricle was positive in 36.8%. Intraoperative abrupt changes in blood pressure and/or heart rate were identified in 19.4% and 17.8% of cases. The clinical resolution of CM was rated to be complete, significant resolution, slight improvement, no improvement and deterioration in 56.0%, 8.0%, 20.0%, 14.0% and 2.0%, respectively. In the cohort of children who experienced post-operative CM as compared to their no-CM counterpart, proportionally more tumors were felt to be adherent to the floor of the 4th ventricle (56.0% vs 49.5%), intraoperative extent of resection was a GTR (74% vs 68.8%) and changes in heart rate were noted (≥ 20% from baseline) (26.0% vs 15.9%). However, a multiple regression analysis identified only abrupt changes in HR (OR 5.97, CI (1.53, 23.1), p = 0.01) to be significantly associated with the development of post-operative CM. CONCLUSION: As a devastating surgical complication after posterior fossa tumor surgery with variable clinical course, identifying and understanding the operative cues and revising intraoperative plans that optimizes the child's neurooncological and clinical outcome are essential.

Characterising the Long-Term Language Impairments of Children Following Cerebellar Tumour Surgery by Extracting Psycholinguistic Properties from Spontaneous Language.

Following cerebellar tumour surgery, children may suffer impairments of spontaneous language. Yet, the language processing deficits underlying these impairments are poorly understood. This study is the first to try to identify these deficits for four levels of language processing in cerebellar tumour survivors. The spontaneous language of twelve patients who underwent cerebellar tumour surgery (age range 3-24 years) was compared against his or her controls using individual case statistics. A distinction was made between patients who experienced postoperative cerebellar mutism syndrome (pCMS) and those who did not. Time since surgery ranged between 11 months and 12;3 years. In order to identify the impaired language processing levels at each processing level (i.e., lexical, semantic, phonological and/or morphosyntactic) nouns and verbs produced in the spontaneous language samples were rated for psycholinguistic variables (e.g., concreteness). Standard spontaneous language measures (e.g., type-token ratio) were calculated as well. First, inter-individual heterogeneity was observed in the spontaneous language outcomes in both groups. Nine out of twelve patients showed language processing deficits three of whom were diagnosed with pCMS. Results implied impairments across all levels of language processing. In the pCMS-group, the impairments observed were predominantly morphosyntactic and semantic, but the variability in nature of the spontaneous language impairments was larger in the non-pCMS-group. Patients treated with cerebellar tumour surgery may show long-term spontaneous language impairments irrespective of a previous pCMS diagnosis. Individualised and comprehensive postoperative language assessments seem necessary, given the inter-individual heterogeneity in the language outcomes.

It's about more than just talking; Exploring computer-mediated communication in adolescents with selective mutism.

INTRODUCTION: Selective mutism (SM) is an anxiety disorder categorized by a persistent failure to speak in specific situations. In an attempt to facilitate interaction with individuals with SM, other forms of communication (e.g. computer-mediated communication; CMC) are often tried. However, CMC is understudied in individuals with SM, while, especially since the COVID-19 pandemic, the importance of CMC for education and social purposes only increased. METHODS: In this study, we explored CMC in 79 adolescents with either selective mutism (n = 34), or typical development (n = 45). All participants completed a survey concerning verbal and written CMC in three contexts (friends, family, and school). RESULTS: Results showed that adolescents with SM used not only verbal but also written CMC less frequently than the comparison group across contexts. While the comparison group preferred Face-to-Face communication over CMC, adolescents with SM were divided, especially in the school context. With family and friends, the majority of the SM group preferred Face-to-Face communication, even though this provoked more feelings of tension than CMC for part of the group. CONCLUSION: These findings support anecdotal reports that SM affects not only speech but extends to other communicative venues and includes written communication in many situations. This underlines the importance of addressing not just speaking behavior but also writing and CMC in the diagnostic evaluation and treatment plans for adolescents with SM.

Selective mutism in immigrant families: An ecocultural perspective.

Although the diagnosis of selective mutism (SM) is more prevalent among immigrant children, the link between the disorder and an immigration background has been elusive. Guided by ecocultural models of development, the current study aimed to construct a theory-based description of SM while considering individual, family, and contextual risk factors. Participants were 78 children with SM (38.4% with an immigration background), and 247 typically developed children (18.2% with an immigration background). Consistent with previous studies, our results suggest that anxiety was the most important predictor of SM symptoms, above and beyond immigration background. Immigration, especially if coupled with bilingual status and low family income, predicted increased levels of SM symptoms. Identifying multi-level predictors of SM may help researchers and clinicians to improve early identification and treatment of SM in culturally and linguistically diverse children.

Application of the Rotterdam postoperative cerebellar mutism syndrome prediction model in patients undergoing surgery for medulloblastoma in a single institution.

OBJECTIVE: Postoperative cerebellar mutism syndrome (CMS) develops in up to 40% of children with medulloblastoma. The Rotterdam model (RM) has been reported to predict a 66% risk of CMS in patients with a score of ≥ 100. The aim of this study was to retrospectively apply the RM to an independent cohort of patients with newly diagnosed medulloblastoma and study the applicability of the RM in predicting postoperative CMS. METHODS: Participants had to have their first tumor resection at the authors' institution and be enrolled in the SJMB12 protocol (NCT01878617). All participants underwent structured serial neurological evaluations before and then periodically after completing radiation therapy. Imaging was reviewed by the study neurologist who was blinded to CMS status when reviewing the scans and retrospectively applied RM score to each participant. RESULTS: Forty participants were included (14 females and 26 males). Four (10%) patients had CMS. The median age at tumor resection was 11.7 years (range 3.5-17.8 years). Tumor location was midline in 30 (75%), right lateral in 6 (15%), and left lateral in 4 (10%). The median Evans index was 0.3 (range 0.2-0.4), and 34 (85%) patients had an Evans index ≥ 0.3. Five participants required a ventricular shunt. The median tumor volume was 51.97 cm3 (range 20.13-180.58 cm3). Gross-total resection was achieved in 35 (87.5%) patients, near-total resection in 4 (10%), and subtotal in 1. The median RM score was 90 (range 25-145). Eighteen participants had an RM score of ≥ 100, and of these 16.7% (n = 3) had CMS. Of the 22 patients with an RM score < 100, 1 child developed CMS (4.5%, CI 0.1%-22.8%); 3 of the 18 patients with an RM score ≥ 100 developed CMS (16.7%, CI 3.6%-41.4%). The observed rate of CMS in the cohort of children with an RM score ≥ 100 was significantly lower than the observed rate in the original RM cohort (66.7%, CI 51%-80.0%, p < 0.001). A greater risk of CMS in patients with an RM score ≥ 100 could not be confirmed (p = 0.31). CONCLUSIONS: At the authors' institution, the incidence of CMS in patients who had an RM ≥ 100 was significantly lower than the RM cohort. These findings raise questions regarding generalizability of RM; however, fewer cases of CMS and a relatively small cohort limit this conclusion.

Diffusion Tensor Imaging Technique Delineating the Prognosis for Cerebellar Mutism in Posterior Fossa Tumors: A New Tool.

AIM: Cerebellar mutism syndrome (CMS) is a morbid complication of posterior fossa surgery in children. This review focuses on the current understanding of pathophysiology in the white matter tracts (WMT) using diffusion tensor imaging (DTI). MATERIAL AND METHODS: A series of 38 patients operated on for posterior fossa tumors in our institute between December 2019 till May 2021 were evaluated neurologically along with characteristics of mutism and DTI imaging (fractional anisotropy) in preoperative and postoperative periods. We also noted tumor size, location, volume, brainstem compression, cerebellar peduncle involvement, extent of resection, surgical approach, and histopathology. RESULT: Cerebellar mutism developed in five patients. The mean age, male sex, tumor size >5 cm, superior cerebellar peduncle involvement, and vermian incision were found to have positive correlation with the development of CMS. They showed reduction in fractional anisotropy in superior cerebellar peduncle (SCP) following resection; however, others' WMT did not show any significant change in fractional anisotropy values pre- or post-surgery. CONCLUSION: Our study suggests that functional disruption of WMT, i.e., superior cerebellar peduncle and dentato-thalamo-cortical tract (DTC) is the underlying pathophysiological component of CMS. Taking this into consideration, we need to deploy techniques to limit the damage to the superior cerebellar peduncle and DTC using neurophysiological monitoring.

Long-term outcomes of selective mutism: a systematic literature review.

BACKGROUND: Selective mutism (SM) is a childhood onset anxiety disorder, and the main symptom is not speaking in certain social situations. Knowledge about the duration and long-term outcomes of SM have been lacking and the aim of this systematic literature review was to address this gap in the literature. We investigated how long SM symptoms persisted as well as other psychiatric outcomes associated with SM in later life. METHODS: The PubMed, PsycInfo, Web of Science, Cochrane Library and Embase databases were initially searched from inception to 11 September 2023. Studies were included if they were published in English and had followed up subjects with clinically diagnosed SM for at least two years. The review followed the Preferred Reporting Items of Systematic Reviews and Meta-analyses guidelines and the protocol was registered with the Open Science Framework. The papers were assessed using the Quality Assessment with Diverse Studies tool. RESULTS: This review screened 2,432 papers and assessed 18 studies. Seven case series studies were excluded from discussion because of the low number of subjects and the fact that their findings could not be generalized to wider populations. In the end, nine clinical cohorts and two case control studies were reviewed. These provided a total of 292 subjects and the sample sizes ranged from 11-49. The overall quality of the studies was moderate. The review found that 190 of the 243 subjects in the studies that reported recovery rates showed moderate or total improvement from SM during follow up. Other anxiety disorders were the most common psychiatric disorders later in life, although these results should be interpreted with caution. Older age at baseline and parental psychopathology might predict greater impairment, but further studies are needed to confirm these results. CONCLUSIONS: Most subjects with SM recovered from this disorder during adolescence, but anxiety disorders were common in later life. Early detection and treatment are needed to prevent symptoms from persisting and other psychiatric disorders from developing.