Neuroimaging and clinical features of bilateral Wallerian degeneration of middle cerebellar peduncles subsequent to pontine infarction.

OBJECTIVE: Wallerian degeneration (WD) of the middle cerebellar peduncles (MCPs) following pontine infarction is a rare secondary degenerative neurological condition. Due to its infrequency, there is limited research on its characteristics. METHODS: This study aims to present three cases of WD of MCPs following pontine infarction and to analyze the prognosis, clinical manifestations, and neuroimaging features by amalgamating our cases with previously reported ones. RESULTS: The cohort consisted of 25 cases, comprising 18 men and 7 women aged 29 to 77 years (mean age: 66.2 years). The majority of patients (94%) exhibit risk factors for cerebrovascular disease, with hypertension being the primary risk factor. Magnetic resonance imaging (MRI) can detect WD of MCPs within a range of 21 days to 12 months following pontine infarction. This degeneration is characterized by bilateral symmetric hyperintensities on T2/FLAIR-weighted images (WI) lesions in the MCPs. Moreover, restricted diffusion, with hyperintensity on diffusion-weighted imaging (DWI) and low apparent diffusion coefficient (ADC) signal intensity may be observed as early as 21 days after the infarction. Upon detection of WD, it was observed that 20 patients (80%) remained asymptomatic during subsequent clinic visits, while four (16%) experienced a worsening of pre-existing symptoms. CONCLUSIONS: These findings underscore the importance of neurologists enhancing their understanding of this condition by gaining fresh insights into the neuroimaging characteristics, clinical manifestations, and prognosis of individuals with WD of bilateral MCPs.

Significant tumor compression of the middle cerebellar peduncle is associated with worse facial nerve outcomes and lower extent of resection in surgery for medium-sized vestibular schwannomas - A radiographic analysis of a case series.

BACKGROUND AND OBJECTIVE: Optimizing the extent of resection (EOR) and facial nerve outcomes (FNO) remain a challenge in medium to large vestibular schwannomas (VS). Currently, tumor size has been the only consistently reported factor predicting FNO and EOR. Here, we sought to evaluate whether the degree of the tumor's compression on the middle cerebellar peduncle (PC) influences FNO and EOR in medium to large VS. METHODS: This retrospective case series included 99 patients who underwent surgical resection of their VSs from 2014 to 2022. Preoperative MR imaging was used to measure the degree of PC. Patient medical records were queried to determine the EOR and FNO. RESULTS: Patients with unfavorable FNO (HB 3 +) immediately post-op had significantly greater PC than those with favorable FNO (19.9 vs. 15.4 mm, P = .047). This significance was not observed at the last follow-up but there was a trend. When medium-sized tumors (15-30 mm) were analyzed separately, patients with unfavorable FNO immediate post-op and at last follow-up had significantly greater PC than their favorable counterparts (14.1 vs 8.7 mm). Significantly greater PC was also observed in patients who underwent subtotal resection (20.7 mm) compared to near (14.3 mm) and gross total resection (10.8 mm). Multivariate analyses confirmed these findings in medium-sized tumors, but not large-sized tumors. CONCLUSION: The degree of PC as measured on preoperative imaging can predict FNO and EOR in medium-sized vestibular schwannomas. Medium-sized tumors with > 15 mm of PC likely will have worse FNO and lower EOR.

Diagnostic efficacy of the magnetic resonance T1w/T2w ratio for the middle cerebellar peduncle in multiple system atrophy and spinocerebellar ataxia: A preliminary study.

BACKGROUND: The standardized T1-weighted/T2-weighted (sT1w/T2w) ratio for the middle cerebellar peduncle (MCP) has been reported to be sensitive for detecting degenerative changes in the cerebellar subtype of multiple system atrophy (MSA-C), even in the early stages. We aimed to investigate the diagnostic value of the MCP sT1w/T2w ratio for differentiating between MSA-C and spinocerebellar ataxia (SCA). METHODS: We included 32 MSA-C, 8 SCA type 3 (SCA3), 16 SCA type 6 (SCA6) patients, and 17 controls, and the MCP sT1w/T2w ratio was analyzed using a region-of-interest approach. The diagnostic performance of the MCP sT1w/T2w ratio in discriminating among MSA-C, SCA3, and SCA6 was assessed and compared with diagnosis based on visual interpretation of MCP hyperintensities and the "hot cross bun" (HCB) sign. RESULTS: MCP sT1w/T2w ratio values were markedly lower in patients with MSA-C than in those with SCA3, those with SCA6, and controls (p < 0.001). The MCP sT1w/T2w ratio showed high diagnostic accuracy for distinguishing MSA-C from SCA3 (area under curve = 0.934), SCA6 (area under curve = 0.965), and controls (area under curve = 0.980). The diagnostic accuracy of the MCP sT1w/T2w ratio for differentiating MSA-C from SCA3 or SCA6 (90.0% for MSA-C vs. SCA3, and 91.7% for MSA-C vs. SCA6) was comparable to or superior than that of visual interpretation of MCP hyperintensities (80.0-87.5% in MSA-C vs. SCA3 and 87.6-97.9% in MSA-C vs. SCA6) or the HCB sign (72.5-80.0% in MSA-C vs. SCA3 and 77.1-93.8% in MSA-C vs. SCA6). CONCLUSIONS: The MCP sT1w/T2w ratio might be a sensitive imaging-based marker for detecting MSA-C-related changes and differentiating MSA-C from SCA3 or SCA6.

Primary intracranial germ cell tumour originating from right brachium Pontis with hypertrophic Olivary degeneration: a case report.

BACKGROUND: Primary right brachium pontis germinoma with hypertrophic olivary degeneration (HOD) is extremely rare. A preoperative diagnosis is challenging due to the absence of characterized clinical and neuroimaging features, and biopsy should be considered. CASE PRESENTATION: A 20-year-old male patient presented with a case of primary intracranial germinoma originating from right brachium pontis with HOD manifesting as ocular myoclonus, nystagmus in both eyes, ataxic gait and incoordination of the limbs. Magnetic resonance imaging (MRI) revealed an irregular patchy lesion with hyperintensity on T2-weighted images (T2WI) and T2 fluid-attenuated inversion recovery (FLAIR) without enhancement by gadolinium (Gd). Furthermore, a focal hyperintense nodule on T2WI in the left inferior olive nucleus (ION) of the medulla oblongata was considered hypertrophic olivary degeneration (HOD) based on the patient's symptoms and neuroimaging findings. Due to suspected demyelinating disease and low-grade glioma (LGG), a biopsy was planned. The pathological diagnosis was germinoma. Subsequently, he received chemoradiation therapy, resulting in the improvement of neurological deficits and the disappearance of the lesion on MRI. CONCLUSION: A case of "Primary right brachium pontis germinoma with HOD" is reported for the first time. A preoperative diagnosis is challenging due to the fact of absence of clinical signs and symptoms and neuroimaging characteristics. However, patients can have favourable prognoses with appropriate evaluation and treatment.

Characterization and diagnostic potential of diffusion tractography in multiple system atrophy.

INTRODUCTION: Microstructural integrity of the middle cerebellar peduncle (MCP) and the putamen captured by diffusion-tensor imaging (DTI) is differentially affected in the parkinsonian and cerebellar variants of multiple system atrophy (MSA-P, MSA-C) compared to Parkinson's disease (PD). The current study applied DTI and tractography in order to 1) characterize the distribution of DTI metrics along the tracts of the MCP and from the putamen in MSA variants, and 2) evaluate the usefulness of combining these measures for the differential diagnosis of MSA-P against PD in the clinical setting. METHODS: Twenty-nine MSA patients (MSA-C, n = 10; MSA-P, n = 19), with a mean disease duration of 2.8 ± 1.7 years, 19 PD patients, and 27 healthy controls (HC) were included in the study. Automatized tractography with a masking procedure was employed to isolate the MCP tracts. DTI measures along the tracts of the MCP and within the putamen were acquired and jointly used to classify MSA vs. PD, and MSA-P vs. PD. Putamen volume was additionally tested as classification feature in post hoc analyses. RESULTS: DTI measures within the MCP and putamen showed significant alterations in MSA variants compared to HC and PD. Classification accuracy for MSA vs. PD and MSA-P vs PD using diffusion measures was 91.7% and 89.5%, respectively. When replacing the putaminal DTI measure by a normalized measure of putamen volume classification accuracy improved to 95.8% and 94.7%, respectively. CONCLUSION: Multimodal information from MCP tractography and putamen volume yields excellent diagnostic accuracy to discriminate between early-to-moderately advanced patients with MSA and PD.

Outcomes at 6 months are related to brain structural and white matter microstructural reorganization in idiopathic tinnitus patients treated with sound therapy.

This study aimed to explore brain structural and white matter microstructural reorganization in the early stage of tinnitus and identify brain alterations that contribute to its relief after 6 months of sound therapy. We studied 64 patients with idiopathic tinnitus, including 29 patients who were categorized into an effective group (EG) and 35 who were categorized into an ineffective group (IG) according to the 6-month follow-up improvement of the Tinnitus Handicap Inventory score, along with 63 healthy controls (HCs). All participants underwent structural and diffusion tensor imaging scanning on a 3-T magnetic resonance system. Differences in brain gray/white matter volume and white matter microstructure were evaluated using voxel-based morphometry analysis and tract-based spatial statistics among the three groups. Associations between brain reorganization and the improvement of tinnitus symptoms were also investigated. Compared with EG patients, IG patients experienced a significant gray matter volume decrease in the right middle frontal gyrus (MFG)/right precentral gyrus (PreCG). Meanwhile, both EG and IG patients showed significant changes (decrease or increase) in brain white matter integrity in the auditory-related or nonauditory-related white matter fiber tracts compared with HCs, while EG patients showed decreased axial diffusivity in the bilateral middle cerebellar peduncle (MCP) compared with IG patients. We combined the gray matter change of the MFG/PreCG and the white matter integrity of the bilateral MCP as an imaging indicator to evaluate the patient's prognosis and screen patients before treatment; this approach reached a sensitivity of 77.1% and a specificity of 82.8%. Our study suggests that there was a close relationship between brain reorganization and tinnitus improvement. The right MFG/PreCG and bilateral MCP may be indicators that can be used to predict prognoses in patients with idiopathic tinnitus and may be used to screen patients before sound therapy. These findings may provide new useful information that can lead to a better understanding of the tinnitus mechanism.

Hypertrophic olivary degeneration concomitant with bilateral middle cerebellar peduncles Wallerian degeneration following unilateral pontine infarction.

BACKGROUND: Wallerian degeneration (WD) can occur in different projecting systems, such as corticospinal tract, dentate-rubro-olivary pathway, and corticopontocerebellar tract. However, the co-occurrence of hypertrophic olivary degeneration (HOD) and middle cerebellar peduncles (MCPs) degeneration secondary to unilateral pontine infarction in a single patient is extremely rare. CASE PRESENTATION: A 71-year-old man presented with acute onset of dizzness, slurred speech, and right-sided weakness. On the next day, his previous neurologic deficits deteriorated. Brain magnetic resonance imaging (MRI) revealed acute ischemic stroke of the left pons. After treatment with thrombolysis, antiplatelets, and rehabilitation training, his speaking and motor function improved moderately. At the 3-month follow-up, the MRI showed hyperintensity in the left medulla oblongata and bilateral MCPs on T2-weighted and FLAIR images, suggesting HOD as well as MCPs degeneration. CONCLUSIONS: It is of great importance for us to know the anatomic knowledge of dentate-rubro-olivary and corticopontocerebellar pathways.

The cerebellum in idiopathic cervical dystonia: A specific pattern of structural abnormalities?

INTRODUCTION: In recent years, cerebellar abnormalities have gained increasing attention as possible physiopathological substratum of idiopathic cervical dystonia (ICD), but a consistent pattern of cerebellar structural modifications has not yet been established. We systematically investigated the presence of volumetric alterations of cerebellar gray (GM) and white matter (WM) in ICD patients, as well as their clinical relevance. METHODS: In this two-centers prospective cross-sectional study, from May 2013 to December 2017, 27 patients with ICD and 27 age- and sex-comparable healthy controls underwent brain MRI including 3D T1-weighted sequences for volumetric analyses. Between-group differences in terms of gray matter and cerebellar peduncles volumes were investigated using both region of interest (ROI)-based and voxel-based approaches using the SUIT tool (SPM12), and significant volumetric changes were correlated with clinical impairment (as measured with the Tsui score) and presence of tremor. RESULTS: ICD patients showed significant volumetric reduction of cerebellar GM in the anterior lobe and lobule VI, resulting from both ROI-based (p ≤ 0.009) and voxel-based (p ≤ 0.04) analyses, while small clusters of reduced WM volume were found in the right cerebellum and left midbrain (p = 0.04), along with reduced volume of the bilateral superior (p = 0.04) and middle (p = 0.03) cerebellar peduncles. Furthermore, higher middle cerebellar peduncles volume was associated with the presence of tremor (p = 0.04). CONCLUSION: Our data show evidence of a specific pattern of cerebellar structural abnormalities in ICD patients, with volume loss mainly involving cortical GM regions related to the somatotopic representation of the affected body parts and, to a lesser extent, cerebellar peduncles.

Evaluation of Clinical Features and Stroke Etiology in Patients with Bilateral Middle Cerebellar Peduncle Infarction.

OBJECTIVE: The aim of this study was to characterize clinical features, etiologies, and mechanisms of strokes due to bilateral middle cerebellar peduncle infarction (BMCPI). METHODS: Cases diagnosed as BMCPI in our hospital were retrieved, and a literature review was performed. Data on clinical features and brain MRI were obtained. Extracranial and intracranial segments of the vertebrobasilar artery were assessed by using digital subtraction angiography, magnetic resonance angiography, or computed tomography angiography. RESULTS: Thirteen cases (11 men and 2 women) of BMCPI were identified. A high-intensity signal of diffusion-weighted imaging sequence involving the bilateral middle cerebellar peduncle was observed in all patients. Most patients experienced vertigo, dysarthria, ataxia, and hearing disorders. Eleven of these cases were classified as large artery atherosclerosis, one as traumatic vertebral artery (VA) dissection, and one as giant cell arteritis. CONCLUSION: BMCPI is a rare cerebrovascular disease characterized by vertigo, ataxia, and dysarthria, which may also be accompanied by a hearing deficit or clinical signs of brainstem damage. BMCPI may be associated with hypoperfusion secondary to occlusive disease of the bilateral VA or proximal basilar artery.

3-dimensional computer graphics model elucidating involvement of intraparenchymal venous malformation in trigeminal nucleus of brachium pontis with intractable trigeminal neuralgia.

Venous malformation (VM) in the posterior cranial fossa occasionally cause trigeminal neuralgia (TN), which were treated with microvascular decompression of its drainer, whereas it was effective only in the limited cases, and its pathological mechanism causing TN is controversial. A 72-year-old man had a 20-year history of typical but severe TN in his left face. Without radiographic evidence of vascular compression on the root entry zone (REZ) of the trigeminal nerve, he underwent stereotactic radiosurgery in previous hospital, resulting in only temporary improvement. On T1-wighted magnetic resonance image with enhancement, the left trigeminal nerve was focally enhanced, which was typical finding after high dose irradiation for TN. Simultaneously, it disclosed small "caput medusa" within the pontine tegmentum, indicated existence of VM in brachium pontis. A 3-dimensional computer graphics model created by fusion of magnetic resonance angiography, diffusion tensor tractography, and fast imaging employing steady-state acquisition elucidated VM was located in the trigeminal nucleus of brachium pontis, which will be very useful for understanding the anatomic correlation of VM and pontine trigeminal nucleus. Since there was no vascular compression at the REZ of the trigeminal nerve, microvascular decompression was not indicated. With minimum dose of gabapentine and carbamazepin, his facial pain completely disappeared and controlled for more than 5 years.

The cerebellar form of acquired hepatocerebral degeneration: The hepatic ataxia.

This article reports a patient with acquired hepatocerebral degeneration that presented with progressive cerebellar ataxia, cerebellar atrophy, and middle cerebellar peduncle lesions. He had a marked improvement after liver transplantation. We reinforce that hepatic failure should be investigated in patients with pure cerebellar syndrome, resembling neurodegenerative diseases.

Brain MRI of multiple system atrophy of cerebellar type: a prospective study with implications for diagnosis criteria.

AIM: The second consensus statement for the diagnosis of multiple system atrophy type cerebellar (MSA-C) includes pons and middle cerebellar peduncle (MCP) atrophy as MRI features. However, other MRI abnormalities such as MCP hyperintensity, hot cross bun sign (HCB), putaminal hypointensity and hyperintense putaminal rim have been described. OBJECTIVES: To evaluate, in patients with sporadic late-onset cerebellar ataxia (SLOCA), the discriminative value of several MRI features for the diagnosis of MSA-C, to follow their evolution during the course of MSA-C, and to search for correlations between these MRI features and clinical signs. METHODS: Consecutive patients referred for SLOCA underwent comprehensive clinical evaluation and laboratory investigations, brain MRI, DaTscan and a 1-year follow-up. RESULTS: Among 80 patients, 26 had MSA-C, 22 another diagnosis, and 32 no diagnosis at the end of the follow-up. At baseline, MCP hyperintensity and HCB were more frequent in patients finally diagnosed with MSA-C than in other patients with SLOCA (p < 0.0001), and had the highest specificity (98.5%) and positive predictive value (91.7%) for the diagnosis of MSA-C, compared to all other MRI signs. The most relevant MRI sequence regarding HCB sign was the T2-proton density (DP) weighted. All MRI features were more frequent with disease duration. No correlation was found between any MRI feature and neither clinical data, nor dopaminergic neuronal loss (p = 0.5008), except between vermis atrophy and UPDRSIII score. CONCLUSION: MCP hyperintensity and HCB sign should be added into the list of additional features of possible MSA-C. MRI signal abnormalities suggestive of MSA-C should be searched for in suitable sequence.

POLR3A-related spastic ataxia: new mutations and a look into the phenotype.

Adolescent-onset spastic ataxia is a proposed novel phenotype in compound heterozygous carriers of an intronic mutation (c.1909 + 22G > A) in the POLR3A gene. Here, we present ten new cases of POLR3A-related spastic ataxia and discuss the genetic, clinical and imaging findings. Patients belonged to six pedigrees with hereditary spastic paraplegia or cerebellar ataxia of unknown origin. All affected subjects presented with compound heterozygous variants, comprising c.1909 + 22G > A in combination in each pedigree with one of the following novel mutations (Thr596Met, Tyr665LeufsTer11, Glu198Ter, c.646-687_1185 + 844del). The new mutations segregated with the phenotype in all families. The phenotype combined variable cerebellar ataxia, gait and lower limb spasticity, involvement of central sensory tracts and in some cases also intention tremor. The reportedly characteristic hyperintensity along the superior cerebellar peduncle on MRI was observed in ~ 80% of the cases. Our study extends the clinical and molecular phenotype further supporting the pathogenic role of the c.1909 + 22G4A intronic mutation and identifying four novel causative mutations in POLR3A-related spastic ataxia. Certain characteristic MRI features may be useful to guide genetic diagnosis.

Degeneration of the Inferior Cerebellar Peduncle After Middle Cerebral Artery Stroke: Another Perspective on Crossed Cerebellar Diaschisis.

Background and Purpose- Deafferentation of the cortico-ponto-cerebellar pathway has been proposed as a key mechanism of crossed cerebellar diaschisis. Although the cerebellum receives afferent stimuli from both cortico-ponto-cerebellar and spinocerebellar pathways, evidence on whether spinocerebellar deafferentation contributes to a hypofunctional cerebellum is lacking. Therefore, we aimed to determine whether changes in the spinocerebellar pathway occur after middle cerebral artery stroke. Methods- Twenty-three patients admitted to our inpatient rehabilitation facility and 23 age-matched healthy controls were retrospectively enrolled. Patients' functional ambulation category was determined and the Medical Research Council muscle scale test of the lower limb muscles was performed at admission and discharge. The fractional anisotropy (FA) values of the corticospinal tract and the inferior cerebellar peduncle (ICP), as the final route of the dorsal spinocerebellar pathway, were compared between the groups. The FA laterality indices of the ICP and corticospinal tract were calculated as follows: (FAaffected-FAunaffected)/(FAaffected+FAunaffected). Pearson correlation analysis and multivariate linear regression models were used to determine the associations between the FA laterality indices and ambulatory function. Results- The FAs of the corticospinal tract and ICP were lower in the patient group than in the control group. The FA laterality index of the corticospinal tract was not correlated with the functional ambulation category or Medical Research Council muscle scale score at admission or discharge. The FA laterality index of the ICP at the pontomedullary junction was positively correlated with the functional ambulation category and Medical Research Council muscle scale scores of all hemiplegic lower limb muscles at admission and discharge. The FA laterality index of the ICP at the pontomedullary junction was independently associated with the functional ambulation category according to the multivariate regression models. Conclusions- ICP degeneration occurs in the subacute and early chronic phase of middle cerebral artery stroke. The lower FA laterality index of the ICP was indicative of poorer ambulatory and lower limb function.

Eye movement abnormalities in middle cerebellar peduncle strokes.

The middle cerebellar peduncle (MCP) is a major conduit for cortico-ponto-cerebellar fibers that convey information related to eye movements. This study aims to elucidate eye movement abnormalities that arise from lesions confined to the MCP. In 23 patients with acute strokes restricted to unilateral MCPs, we investigated the clinical features and ocular motor findings including spontaneous nystagmus, saccades, smooth pursuit, ocular tilt reaction, and head impulse tests. Bithermal caloric tests and audiometry were also performed. Patients with strokes restricted to the MCP usually developed acute vertigo or imbalance, along with few sensorimotor signs or auditory symptoms. Patients frequently showed abnormal eye movements that included spontaneous horizontal/torsional nystagmus, ocular tilt reaction, gaze-evoked nystagmus, abnormal head impulse responses, and bilaterally impaired horizontal smooth pursuit. Unilateral MCP strokes produce acute vertigo and imbalance with distinct ocular motor abnormalities, which are primarily caused by damage to the central vestibular structures and by disruption of the neural pathways responsible for eye-position stabilization and smooth pursuit.

Brain white matter microstructural alterations in children of type I Gaucher disease characterized with diffusion tensor MR imaging.

OBJECTIVES: To investigate white matter (WM) microstructural alterations in type I Gaucher disease (type I GD) pediatric patients and explore the correlation between the disease duration and WM changes. METHODS: Twenty-two GD patients and twenty-two sex- and age-matched typical development (TD) children were recruited. Changes in WM were investigated using diffusion tensor imaging (DTI) and applying atlas-based tract analysis. For all DTI measurements, independent-samples t-test was applied to report significant differences between type I GD and TD. Partial correlation was applied to determine whether the disease duration was correlated with DTI measurements. RESULTS: Bidirectional fractional anisotropy (FA) changes were found in the bilateral superior cerebellar peduncle, right posterior limb of the internal capsule, right posterior corona radiata, and right posterior thalamic radiation (p < 0.05). Higher mean diffusivity (MD)was found in the right superior corona radiata, middle cerebellar peduncle, right posterior thalamic radiation and right superior longitudinal fasciculus (p < 0.05) in type I GD. And higher radial diffusivity (RD) was also found in the left superior cerebellar peduncle (p < 0.05) in type I GD. The disease duration of type I GD patients is positively correlated with axial diffusivity and MD in multiple major WM tracts. CONCLUSION: DTI findings supported the microstructural alterations of multiple WM tracts in type I GD patients.

Bilateral effects of unilateral cerebellar lesions as detected by voxel based morphometry and diffusion imaging.

Over the last decades, the importance of cerebellar processing for cortical functions has been acknowledged and consensus was reached on the strict functional and structural cortico-cerebellar interrelations. From an anatomical point of view strictly contralateral interconnections link the cerebellum to the cerebral cortex mainly through the middle and superior cerebellar peduncle. Diffusion MRI (dMRI) based tractography has already been applied to address cortico-cerebellar-cortical loops in healthy subjects and to detect diffusivity alteration patterns in patients with neurodegenerative pathologies of the cerebellum. In the present study we used dMRI-based tractography to determine the degree and pattern of pathological changes of cerebellar white matter microstructure in patients with focal cerebellar lesions. Diffusion imaging and high-resolution volumes were obtained in patients with left cerebellar lesions and in normal controls. Middle cerebellar peduncles and superior cerebellar peduncles were reconstructed by multi fiber diffusion tractography. From each tract, measures of microscopic damage were assessed, and despite the presence of unilateral lesions, bilateral diffusivity differences in white matter tracts were found comparing patients with normal controls. Consistently, bilateral alterations were also evidenced in specific brain regions linked to the cerebellum and involved in higher-level functions. This could be in line with the evidence that in the presence of unilateral cerebellar lesions, different cognitive functions can be affected and they are not strictly linked to the side of the cerebellar lesion.