OBJECTIVE: Metronidazole, a widely used antimicrobial medication, has been linked to neurologic adverse drug reactions. This study investigates the association between metronidazole use and first-time neurologic events.
METHODS: We conducted a case-time-control study using data from the Danish National Patient Register and the National Prescription Register in years 2013 to 2021. Patients with a first-time diagnosis of encephalopathy, cerebellar dysfunction, or peripheral neuropathy were included. Conditional logistic regression analyses were performed to estimate the risk of neurologic events associated with metronidazole use.
RESULTS: Out of 476,066 first-time metronidazole prescriptions, the 100-day cumulative incidence of peripheral neuropathy was 0.016%, and 0.002% for cerebellar dysfunction or encephalopathy. In the case-time control study, we identified 17,667 persons with a first-time neurologic event and were included for the analysis. The estimated odds ratio for the combined neurologic events was 0.98 (95% CI, 0.59-1.64, P = 0.95) with no statistically significant association across different subgroups and time windows.
CONCLUSIONS: Our findings suggest that metronidazole-induced neurologic events may be rarer than previously described, and we did not find any consistent or statistically significant association between metronidazole exposure. Nonetheless, clinicians should remain vigilant to potential neurologic risks in patients receiving metronidazole, to ensure its safe and effective use.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: These results provide a foundation of current practices on which to build future intervention-based clinical trials.

Phosphomannomutase deficiency (PMM2-CDG) leads to cerebellar atrophy with ataxia, dysmetria, and intellectual deficits. Despite advances in therapy, the cognitive and adaptive profile remains unknown. Our study explores the adaptive profile of 37 PMM2-CDG patients, examining its association with parental stress and medical characteristics. Assessment tools included ICARS for the cerebellar syndrome and NPCRS for global disease severity. Behavioral and adaptive evaluation consisted of the Vineland Adaptive Behavior Scale and the Health of the Nation Outcome Scales. Psychopathological screening involved the Child Behavior Checklist and the Symptom Check-List-90-R. Parental stress was evaluated using Parental Stress Index. Results were correlated with clinical features. No significant age or sex differences were found. \'Daily living skills\' were notably affected. Patients severely affected exhibited lower adaptive skill values, as did those with lipodystrophy and inverted nipples. Greater severity in motor cerebellar syndrome, behavioral disturbances and the presence of comorbidities such as hyperactivity, autistic features and moderate-to-severe intellectual disability correlated with greater parental stress. Our study found no decline in adaptive abilities. We provide tools to assess adaptive deficits in PMM2-CDG patients, emphasizing the importance of addressing communication, daily living skills, and autonomy, and their impact on parental stress in clinical monitoring and future therapies.

Part of the extra-pyramidal system, the cerebellum is more and more recognized by its non-motor functions known as the cerebellar cognitive affective syndrome. Several studies have identified disturbances specifically in executive and attentional functions after focal cerebellar lesions. However, most studies were performed in small and heterogeneous patient groups. Furthermore, there is a substantial variation in the methodology of assessment. Here, we present the results of a large and homogeneous cohort of patients with isolated uniform cerebellar lesions. After three months post-stroke all patients underwent structural neuroimaging to confirm an isolated lesion and were given neuropsychological testing. The results show that cerebellar lesions relate to mild but long-term cognitive impairment in a broad spectrum of neurocognitive functions compared to normative values. These findings confirm involvement of the cerebellum in cognitive processing and supports the theory of \'dysmetria of thought\' based upon uniform cerebellar processing in multiple cognitive domains. This study highlights the following results: 1-Cognitive impairments after isolated cerebellar stroke is confirmed in several cognitive domains. 2-Semantic and phonemic fluency are most affected in cerebellar stroke patients. 3-Verbal deficits show an age-independent long term effect post-stroke and should be studied further in depth. 4-Cognitive disorders after cerebellar stroke are more prominent in women than men.

OBJECTIVE: Space-occupying cerebellar stroke (SOCS) when coupled with neurological deterioration represents a neurosurgical emergency. Although current evidence supports surgical intervention in such patients with SOCS and rapid neurological deterioration, the optimal surgical methods/techniques to be applied remain a matter of debate.
METHODS: We conducted a retrospective, multicenter study of patients undergoing surgery for SOCS. Patients were stratified according to the type of surgery as (1) suboccipital decompressive craniectomy (SDC) or (2) suboccipital craniotomy with concurrent necrosectomy. The primary end point examined was functional outcome using the modified Rankin Scale (mRS) at discharge and at 3 months (mRS 0-3 defined as favorable and mRS 4-6 as unfavorable outcome). Secondary end points included the analysis of in-house postoperative complications, mortality, and length of hospitalization.
RESULTS: Ninety-two patients were included in the final analysis: 49 underwent necrosectomy and 43 underwent SDC. Those with necrosectomy displayed significantly higher rate of favorable outcome at discharge as compared with those who underwent SDC alone: 65.3% vs 27.9%, respectively ( P < .001, odds ratios 4.9, 95% CI 2.0-11.8). This difference was also observed at 3 months: 65.3% vs 41.7% ( P = .030, odds ratios 2.7, 95% CI 1.1-6.7). No significant differences were observed in mortality and/or postoperative complications, such as hemorrhagic transformation, infection, and/or the development of cerebrospinal fluid leaks/fistulas.
CONCLUSIONS: In the setting of SOCS, patients treated with necrosectomy displayed better functional outcomes than those patients who underwent SDC alone. Ultimately, prospective, randomized studies will be needed to confirm this finding.

Acute basilar artery occlusion (ABAO) after endovascular treatment (EVT) is often associated with a poor prognosis, particularly in patients with cerebellar infarction who may develop malignant cerebellar edema. The present study aimed to investigate how massive cerebellar infarction (MCI) affects hospitalization outcomes in ABVO patients who undergo EVT. We conducted a retrospective study of ABVO patients who underwent EVT at our hospital between September 2017 and September 2022. MCI was diagnosed using imaging techniques, and various prognostic scores were assessed during hospitalization to examine the relationship between MCI and these outcomes. We identified 42 ABAO patients, of whom 22 (52.4%) had MCI. Patients with MCI had a higher modified Rankin Scale (mRS) score at discharge compared to those without MCI (4.36 ± 1.14 vs 3.05 ± 1.85, P = .042, odds ratio [OR] (95% confidence interval [CI]) = 1.093 (0.083, 2.103)), and a lower Glasgow Coma Scale score (6.59 ± 4.0 vs 10.10 ± 5.07, P = .036, OR (95% CI) = -3.444 (-6.518, -0.369)). MCI was identified as an independent risk factor for an extremely poor prognosis (mRS ≥ 5) at discharge (P = .036, OR (95% CI) = 15.531 (1.603, 313.026)) and for no improvement in mRS score compared to onset (P = .013, OR (95% CI) = 0.025 (0.001, 0.274)). Additionally, an extremely poor prognosis was independently associated with stent implantation, EVT duration, and body mass index, while mRS score improvement was correlated with EVT duration and pulmonary infection. MCI in ABAO patients is a significant independent risk factor for a poor prognosis at discharge and no improvement in function score compared to onset. Early diagnosis and intervention are necessary to improve outcomes, particularly in high-risk populations.

The term congenital ocular motor apraxia (COMA), coined by Cogan in 1952, designates the incapacity to initiate voluntary eye movements performing rapid gaze shift, so called saccades. While regarded as a nosological entity by some authors, there is growing evidence that COMA designates merely a neurological symptom with etiologic heterogeneity. In 2016, we reported an observational study in a cohort of 21 patients diagnosed as having COMA. Thorough re-evaluation of the neuroimaging features of these 21 subjects revealed a previously not recognized molar tooth sign (MTS) in 11 of them, thus leading to a diagnostic reassignment as Joubert syndrome (JBTS). Specific MRI features in two further individuals indicated a Poretti-Boltshauser syndrome (PTBHS) and a tubulinopathy. In eight patients, a more precise diagnosis was not achieved. We pursued this cohort aiming at clarification of the definite genetic basis of COMA in each patient.
Using a candidate gene approach, molecular genetic panels or exome sequencing, we detected causative molecular genetic variants in 17 of 21 patients with COMA. In nine of those 11 subjects diagnosed with JBTS due to newly recognized MTS on neuroimaging, we found pathogenic mutations in five different genes known to be associated with JBTS, including KIAA0586, NPHP1, CC2D2A, MKS1, and TMEM67. In two individuals without MTS on MRI, pathogenic variants were detected in NPHP1 and KIAA0586, arriving at a diagnosis of JBTS type 4 and 23, respectively. Three patients carried heterozygous truncating variants in SUFU, representing the first description of a newly identified forme fruste of JBTS. The clinical diagnoses of PTBHS and tubulinopathy were confirmed by detection of causative variants in LAMA1 and TUBA1A, respectively. In one patient with normal MRI, biallelic pathogenic variants in ATM indicated variant ataxia telangiectasia. Exome sequencing failed to reveal causative genetic variants in the remaining four subjects, two of them with clear MTS on MRI.
Our findings indicate marked etiologic heterogeneity in COMA with detection of causative mutations in 81% (17/21) in our cohort and nine different genes being affected, mostly genes associated with JBTS. We provide a diagnostic algorithm for COMA.

Cerebellar mutism syndrome (CMS) is a well-known complication after posterior fossa tumor surgery in pediatric patients. We evaluated the incidence of CMS in our institute and analyzed its association with multiple risk factors, such as tumor entity, surgical approach, and hydrocephalus.
All pediatric patients who had undergone intra-axial tumor resection in the posterior fossa between January 2010 and March 2021 were included in the retrospective analysis. Various data points, including demographic, tumor-associated, clinical, radiological, surgery-associated, complications, and follow-up data, were collected and statistically evaluated for an association with CMS.
A total of 63 surgeries in 60 patients were included. The median patient age was 8 years. Pilocytic astrocytoma was the most common tumor type (50%), followed by medulloblastoma (28%) and ependymomas (10%). Complete, subtotal, and partial resection was achieved in 67%, 23%, and 10%, respectively. A telovelar approach had been used the most often (43%) compared with a transvermian approach (8%). Of the 60 children, 10 (17%) had developed CMS and showed marked improvement but with residual deficits. The significant risk factors were a transvermian approach (P = 0.03), vermian splitting when added to another approach (P = 0.002), an initial presentation with acute hydrocephalus (P = 0.02), and hydrocephalus present after tumor surgery (P = 0.004).
Our CMS rate is comparable to those described in the literature. Despite the limitations of the retrospective study design, we found that CMS was not only associated with a transvermian approach but was also associated with a telovelar approach, although to a lesser extent. Acute hydrocephalus at the initial presentation necessitating urgent management was significantly associated with a greater incidence of CMS.

In this study, the authors aimed to investigate the relationship between postoperative MRI features and cerebellar mutism syndrome.
A retrospective cohort of patients who underwent tumor resection from July 2013 to March 2021 for midline posterior fossa tumors was investigated. All patients were followed up at least once. Clinical data were extracted from medical records and follow-up databases. Two neuroradiologists independently reviewed preoperative and postoperative MRI. Univariable and multivariable analyses were performed to compare the postoperative cerebellar mutism syndrome (pCMS) and non-pCMS groups. Correlation analysis was performed using the Spearman correlation coefficient analysis.
Of 124 patients, 47 (37.9%) developed pCMS. The median follow-up duration was 45.73 (Q1: 33.4, Q3: 64.0) months. The median duration of mutism was 45 days. The median tumor size was 48.8 (Q1: 42.1, Q3: 56.8) mm. In the univariable analysis, abnormal T2-weighted signal of the left dentate nucleus (DN) (74.5% in the pCMS group vs 36.4% in the non-pCMS group, p < 0.001), right DN (83.0% vs 40.3%, p < 0.001), left superior cerebellar peduncle (SCP) (74.5% vs 27.3%, p < 0.001), right SCP (63.8% vs 23.4%, p < 0.001), left middle cerebellar peduncle (MCP) (51.1% vs 26.0%, p = 0.008), and right MCP (61.7% vs 26.0%, p < 0.001); male sex (83.0% vs 45.5%, p < 0.001); vermis 3 impairment (49.4% vs 19.1%, p = 0.002); solid tumor (91.5% vs 72.7%, p = 0.022); and hydrocephalus (72.3% vs 45.5%, p = 0.006) were more frequent in the pCMS group than in the non-pCMS group. Multivariable logistic analysis showed that male sex (adjusted OR 4.08, p = 0.010) and the cerebro-cerebellar circuit score of T2-weighted images (adjusted OR 2.15, p < 0.001) were independent risk factors for pCMS. The cerebro-cerebellar circuit score positively correlated with the duration of mutism. In Cox regression analysis, the cerebro-cerebellar integrated circuit injury score of T2 (adjusted HR 0.790, 95% CI 0.637-0.980; p = 0.032) and injury of vermis 3 (adjusted HR 3.005, 95% CI 1.197-7.547; p = 0.019) were independently associated with the duration of mutism.
Male sex and cerebro-cerebellar circuit damage are independent risk factors for pCMS. The cerebro-cerebellar circuit score indicates the duration of mutism.

In 1967, Andén, Fuxe, and Ungerstedt demonstrated the presence of monoamine-containing fibers in the rat cerebellum. Over the past 50 years, this finding has provided clinical relevance of the noradrenergic system to the cerebellum. Cerebellar dysfunction and noradrenergic system may relate to tremor in Parkinson disease and essential tremor, motor learning, and the vestibulo-ocular reflex in spinocerebellar ataxias. Cognition and emotion may also be linked to the cerebellar noradrenergic system, in relation to the symptoms of Alzheimer disease, dementia with Lewy bodies, and attention-deficit/hyperactivity disorder. Despite recent technological advances in neuroimaging for evaluating the noradrenergic system, we need more evidence to understand the precise pathophysiological relationship between the cerebellum and the noradrenergic system and its clinical implications.