Risk factors for postoperative cerebellar mutism syndrome in pediatric patients: a systematic review and meta-analysis

OBJECTIVE A review article assessing all the risk factors reported in the literature for postoperative cerebellar mutism syndrome (pCMS) among children remains absent. The authors sought to perform a systematic review and meta-analysis to evaluate this issue. METHODS PubMed, Embase, and Web of Science were queried to systematically extract potential references. The articles relating to pCMS were required to be written in the English language, involve pediatric patients (≤ 18 years of age), and provide extractable data, which included a comparison group of patients who did not develop pCMS. The quality of the included studies was evaluated using the Newcastle-Ottawa Scale. Data were pooled using RevMan 5.4, and publication bias was assessed by visual inspection for funnel plot asymmetry. The study protocol was registered through PROSPERO (ID: CRD42021256177). RESULTS Overall, 28 studies involving 2276 patients were included. Statistically significant risk factors identified from univariate analysis were brainstem invasion (OR 4.28, 95% CI 2.23–8.23; p < 0.0001), fourth ventricle invasion (OR 12.84, 95% CI 4.29–38.44; p < 0.00001), superior cerebellar peduncle invasion (OR 6.77, 95% CI 2.35–19.48; p = 0.0004), diagnosis of medulloblastoma (OR 3.26, 95% CI 1.93–5.52; p < 0.0001), medulloblastoma > 50 mm (OR 8.85, 95% CI 1.30–60.16; p = 0.03), left-handedness (OR 6.57, 95% CI 1.25–34.44; p = 0.03), and a vermis incision (OR 5.44, 95% CI 2.09–14.16; p = 0.0005). On the other hand, a tumor located in the cerebellar hemisphere (OR 0.23, 95% CI 0.06–0.92; p = 0.04), cerebellar hemisphere compression (OR 0.23, 95% CI 0.11–0.45; p < 0.0001), and intraoperative imaging (OR 0.36, 95% CI 0.18–0.72; p = 0.004) reduced the risk of pCMS. CONCLUSIONS This study provides the largest and most reliable review of risk factors associated with pCMS. Although some risk factors may be dependent on one another, the data may be used by surgeons to better identify patients at risk for pCMS and for intervention planning.

Understanding Parinaud’s Syndrome

Parinaud’s syndrome involves dysfunction of the structures of the dorsal midbrain. We investigated the pathophysiology related to the signs and symptoms to better understand the symptoms of Parinaud’s syndrome: diplopia, blurred vision, visual field defects, ptosis, squint, and ataxia, and Parinaud’s main signs of upward gaze paralysis, upper eyelid retraction, convergence retraction nystagmus (CRN), and pseudo-Argyll Robertson pupils. In upward gaze palsy, three structures are disrupted: the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF), interstitial nucleus of Cajal (iNC), and the posterior commissure. In CRN, there is a continuous discharge of the medial rectus muscle because of the lack of inhibition of supranuclear fibers. In Collier’s sign, the posterior commissure and the iNC are mainly involved. In the vicinity of the iNC, there are two essential groups of cells, the M-group cells and central caudal nuclear (CCN) group cells, which are important for vertical gaze, and eyelid control. Overstimulation of the M group of cells and increased firing rate of the CCN group causing eyelid retraction. External compression of the posterior commissure, and pretectal area causes pseudo-Argyll Robertson pupils. Pseudo-Argyll Robertson pupils constrict to accommodation and have a slight response to light (miosis) as opposed to Argyll Robertson pupils were there is no response to a light stimulus. In Parinaud’s syndrome patients conserve a slight response to light because an additional pathway to a pupillary light response that involves attention to a conscious bright/dark stimulus. Diplopia is mainly due to involvement of the trochlear nerve (IVth cranial nerve. Blurry vision is related to accommodation problems, while the visual field defects are a consequence of chronic papilledema that causes optic neuropathy. Ptosis in Parinaud’s syndrome is caused by damage to the oculomotor nerve, mainly the levator palpebrae portion. We did not find a reasonable explanation for squint. Finally, ataxia is caused by compression of the superior cerebellar peduncle.

A Young Japanese Patient with Spinocerebellar Ataxia Type 3 Presenting Depressive State with Cenesthopathy and Delusion: a Case Report

Depressive state is a common complication of spinocerebellar ataxia type 3 (SCA3). To the best of our knowledge, cases of SCA3 presenting with cenesthopathy have not been described. Here, we present a case of a severe depressive state with cenesthopathy and delusion in a young Japanese man with SCA3. A 43-year-old Japanese man with SCA3 developed a severe depressive state with associated cenesthopathy and delusion. He was treated with escitalopram (10 mg/day) and olanzapine (2.5 mg/day). Computed tomography showed atrophy of the cerebellum, bilateral superior cerebellar peduncle, and tegmentum of the pons. Single-photon emission computed tomography demonstrated reduced blood flow in the cerebellum, vermis, and brainstem. After 8 weeks, his depressive state and delusion improved; however, his cenesthopathy persisted. We encountered a case of a severe depressive state with cenesthopathy and delusion in a young Japanese man with SCA3. This case supports previous studies that the cerebellum could have a role beyond motor functions.

Another Piece of the Puzzle of Anomalous Connectivity in Joubert's Syndrome

We report on the conventional and diffusion tensor imaging (DTI) findings of a 2-year-old child with clinical presentation of Joubert's Syndrome (JS) and brainstem structural abnormalities as depicted by neuroimaging.Conventional magnetic resonance imaging (MRI) showed a “molar tooth” configuration of the brainstem. A band-like formation coursing in an apparent axial plane anterior to the interpeduncular fossa was noted and appeared to partially cover the interpeduncular fossa.DTI maps and three-dimensional (3D) tractography demonstrated a prominent red-encoded white matter bundle anterior to the midbrain. Probable aberrant course of the bilateral corticospinal tracts (CST) was also depicted. Absence of the decussation of the superior cerebellar peduncles and elongated thickened, horizontal superior cerebellar peduncle (SCP) reflecting the molar tooth sign were also shown.Our report and the review of the published cases suggest that DTI and tractography may be very helpful to differentiate between interpeduncular heterotopias and similarly located white matter bundles corroborating the underlying etiology of axonal guidance disorders in the complex group of ciliopathies including JS. Our case represents an important additional puzzle piece to explore the variability of these ciliopathies.

The brainstem in multiple sclerosis: MR identification of tracts and nuclei damage

Objective To evaluate the 3D Fast Gray Acquisition T1 Inversion Recovery (FGATIR) sequence for MRI identification of brainstem tracts and nuclei damage in multiple sclerosis (MS) patients. Methods From april to december 2020, 10 healthy volunteers and 50 patients with remitted-relapsing MS (58% female, mean age 36) underwent MR imaging in the Neuro-imaging department of the C.H.N.O. des Quinze-Vingts, Paris, France. MRI was achieved on a 3 T system (MAGNETOM Skyra) using a 64-channel coil. 3D FGATIR sequence was first performed on healthy volunteers to classify macroscopically identifiable brainstem structures. Then, FGATIR was assessed in MS patients to locate brainstem lesions detected with Proton Density/T2w (PD/T2w) sequence. Results In healthy volunteers, FGATIR allowed a precise visualization of tracts and nuclei according to their myelin density. Including FGATIR in MR follow-up of MS patients helped to identify structures frequently involved in the inflammatory process. Most damaged tracts were the superior cerebellar peduncle and the transverse fibers of the pons. Most frequently affected nuclei were the vestibular nuclei, the trigeminal tract, the facial nerve and the solitary tract. Conclusion Combination of FGATIR and PD/T2w sequences opened prospects to define MS elective injury in brainstem tracts and nuclei, with particular lesion features suggesting variations of the inflammatory process within brainstem structures. In a further study, hypersignal quantification and microstructure information should be evaluated using relaxometry and diffusion tractography. Technical improvements would bring novel parameters to train an artificial neural network for accurate automated labeling of MS lesions within the brainstem.

Joubert syndrome: a case report

Background Joubert syndrome (JS) is a rare autosomal recessive genetic heterogeneously inherited disorder characterized by neurological features that include hypotonia, ataxia, developmental delay, intellectual disability, abnormal eye movements, and neonatal breathing dysregulation. Case presentation The main purposes of the case report are to highlight the benefit of multidisciplinary rehabilitation team approach and describe the clinical features associated with Joubert syndrome. In this case report, we have discussed a 9-month-old girl who presented with developmental delay, impaired vision, and a history of recurrent respiratory infection with respiratory distress. On examination, she had facial dysmorphism, myopia, and hypotonia. Brain magnetic resonance imaging showed a thick, elongated, and abnormally oriented superior cerebellar peduncle showing molar tooth appearance with elongated bat-wing shaped 4th ventricle and hypoplasia of the vermis suggestive of JS. The patient has been treated at Garden Reach Institute for the Rehabilitation and Research (GRIRR), Kolkata, India, by a multidisciplinary team of physiotherapist, speech therapist, special educator, orthotist, medical officer, and social worker that shown excellent improvement in her condition, and she has achieved good sitting balance, able to sit without support, stand with wall support, and able to walk using bilateral AFO and reverse walker. Conclusion Knowledge of characteristic clinical and radiological findings in JS will help in early diagnosis and successful rehabilitation.

Spatiotemporal changes in along-tract profilometry of cerebellar peduncles in cerebellar mutism syndrome

Aims Cerebellar mutism syndrome occurs in 25% of children following resection of posterior fossa tumours. Characterised by mutism, emotional lability and cerebellar motor signs, the syndrome is usually reversible over weeks to months. Its pathophysiology remains unclear, but evidence from diffusion MRI studies has implicated damage to the superior cerebellar peduncles in the development of this condition. The objective of this study was to describe the application of automated tractography of the cerebellar peduncles to provide a high-resolution spatiotemporal profile of diffusion MRI changes in cerebellar mutism syndrome. Method A retrospective case-control study was performed at Lucille Packard Children’s Hospital, Stanford University. Thirty children with midline medulloblastoma (mean age ± standard deviation 8.8 ± 3.8 years) underwent volumetric T1-weighted and diffusion MRI at four timepoints over one year. Forty-nine healthy children (9.0 ± 4.2 years), scanned at a single timepoint, were included as age- and sex-matched controls. Cerebellar mutism syndrome status was determined by contemporaneous casenote review. Automated Fibre Quantification was used to segment each subject’s cerebellar peduncles (Figure 1), and fractional anisotropy was computed at 30 nodes along each tract. A non-parametric permutation-based method was used to generate a critical cluster size and p-value for by-node ANOVA group comparisons. Z-scores for patients’ fractional anisotropy at each node were calculated based on values from controls’ corresponding nodes; these were analysed using mixed ANOVA with post-hoc false discovery rate-corrected pairwise t-tests. Results 13 patients developed cerebellar mutism syndrome. Automated fibre segmentation successfully identified the cerebellar peduncles in the majority of participants, but was more robust at follow-up timepoints (78.7% vs. 44.7% pre-operatively). Fractional anisotropy was significantly lower in the distal regions of the left superior cerebellar peduncle pre-operatively (p=0.0137) in patients compared to controls, although patients could not be distinguished pre-operatively with respect to cerebellar mutism syndrome status (Figure 2). Post-operative reductions in fractional anisotropy in children with cerebellar mutism syndrome were highly specific to the distal left superior cerebellar peduncle, and were most pronounced at follow-up timepoints (p=0.006; Figure 3). There were no significant differences in other cerebellar peduncles, either in along-tract fractional anisotropy or Z-scores, with respect to cerebellar mutism syndrome status. Conclusion A novel application of an automated tool to extract diffusion MRI data along the length of the cerebellar peduncles is described in a longitudinal retrospective cohort of paediatric medulloblastoma. Changes in fractional anisotropy in the cerebellar peduncles following tumour resection are described in a heretofore unprecedented level of spatiotemporal detail. In particular, children with post-operative cerebellar mutism syndrome show changes in the distal regions of the left superior cerebellar peduncle, and these changes persist up to a year post-operatively. These findings will have direct clinical implications for neurosurgeons performing resection of midline paediatric posterior fossa tumours.

Evaluating and Optimizing Dentato-Rubro-Thalamic-Tract Deterministic Tractography in Deep Brain Stimulation for Essential Tremor

BACKGROUND Dentato-rubro-thalamic tract (DRT) deep brain stimulation (DBS) suppresses tremor in essential tremor (ET) patients. However, DRT depiction through tractography can vary depending on the included brain regions. Moreover, it is unclear which section of the DRT is optimal for DBS. OBJECTIVE To evaluate deterministic DRT tractography and tremor control in DBS for ET. METHODS After DBS surgery, DRT tractography was conducted in 37 trajectories (20 ET patients). Per trajectory, 5 different DRT depictions with various regions of interest (ROI) were constructed. Comparison resulted in a DRT depiction with highest correspondence to intraoperative tremor control. This DRT depiction was subsequently used for evaluation of short-term postoperative adverse and beneficial effects. RESULTS Postoperative optimized DRT tractography employing the ROI motor cortex, posterior subthalamic area (PSA), and ipsilateral superior cerebellar peduncle and dentate nucleus best corresponded with intraoperative trajectories (92%) and active DBS contacts (93%) showing optimal tremor control. DRT tractography employing a red nucleus or ventral intermediate nucleus of the thalamus (VIM) ROI often resulted in a more medial course. Optimal stimulation was located in the section between VIM and PSA. CONCLUSION This optimized deterministic DRT tractography strongly correlates with optimal tremor control. This technique is readily implementable for prospective evaluation in DBS target planning for ET.

A Young Japanese Patient with Spinocerebellar Ataxia Type 3 Presenting Depressive State with Cenesthopathy and Delusion: A Case Report

Background: Depressive state is a common complication of spinocerebellar ataxia type 3 (SCA3). To the best of our knowledge, cases of SCA3 presenting with psychotic symptoms (i.e., cenesthopathy) have not been described. Here, we present a case of severe depressive state with cenesthopathy and delusion in a young Japanese man with SCA3.Case presentation: A 43-year-old Japanese man with SCA3 developed severe depressive state with associated cenesthopathy and delusion. He was treated with escitalopram (10 mg/day) and olanzapine (2.5 mg/day). Computed tomography showed atrophy of the cerebellum, bilateral superior cerebellar peduncle, and tegmentum of the pons. Single-photon emission computed tomography demonstrated reduced blood flow in the cerebellum, vermis, and brainstem. After eight weeks, his depressive state and delusion improved however his cenesthopathy persisted. Conclusions: We encountered a case of severe state with psychotic features (i.e., cenesthopathy and delusion) in a young Japanese man with SCA3. This study demonstrates that SCA3 may inherently present with severe depressive state and unique psychotic symptoms, even in younger patients where age-related neurodegeneration is unlikely. The complex function of the cerebellum in emotion and perception may play a crucial in the emergence of these psychiatric symptoms.

Functional and structural MRI correlates of executive functions in multiple sclerosis

Background: Executive dysfunctions, including difficulties in attention, working memory, planning, and inhibition affect 15%–28% of multiple sclerosis (MS) patients. Objectives: To investigate structural and functional magnetic resonance imaging (MRI) abnormalities underlying executive function (EF) in MS patients. Methods: A total 116 MS patients and 65 controls underwent resting-state (RS) and diffusion-weighted sequences and neuropsychological examination, including Wisconsin Card Sorting Test (WCST) to test EF. Brain RS cognitive networks and fractional anisotropy (FA) from a priori selected white matter tracts were derived. Associations of WCST scores with RS functional connectivity (FC) and FA abnormalities were investigated. Results: In MS patients, predictors of working memory/updating were: lower corpus callosum (CC) FA, lower left working-memory network (WMN), right WMN RS FC for worse performance; lower executive control network (ECN), higher default-mode network (DMN), and salience network (SN) RS FC for better performance ( R2 = 0.35). Predictors of attention were lower CC genu FA, lower left WMN, and DMN RS FC for worse performance; higher left WMN and ECN RS FC for better performance ( R2 = 0.24). Predictors of worse shifting/inhibition were lower CC genu and superior cerebellar peduncle (SCP) FA, lower left WMN RS FC for worse performance; and higher ECN RS FC for better performance ( R2 = 0.24). Conclusions: CC and SCP microstructural damage and RS FC abnormalities in cognitive networks underlie EF frailty in MS.