Search

Cerebellar mutism syndrome (CMS), also known as posterior fossa syndrome, is an entity that entails a constellation of signs and symptoms which are recorded in a limited number of pediatric patients who have been operated on mainly for tumors involving the posterior cranial fossa, and more precisely, the region of the vermis. Medulloblastoma seems to constitute the most commonly recognized pathological substrate, associated with this entity. The most prevalent constituents of this syndrome are noted to be a, often transient, although protracted, language impairment, emotional lability, along with cerebellar and brainstem dysfunction. Apart from that, a definite proportion of involved individuals are affected by irreversible neurological defects and long-lasting neurocognitive impairment. A bulk of literature and evidence based on clinical trials exist, which reflect the continuous effort of the scientific community to highlight all perspectives of this complex phenomenon. There are several circumstances that intervene in our effort to delineate the divergent parameters that constitute the spectrum of this syndrome. In summary, this is implicated by the fact that inconsistent nomenclature, poorly defined diagnostic criteria, and uncertainty regarding risk factors and etiology are all constituents of a non-well-investigated syndrome. Currently, a preliminary consensus exists about the identification of a group of diagnostic prerequisites that are managed as sine qua non, in our aim to document the diagnosis of CMS. These include language impairment and emotional lability, as proposed by the international Board of the Posterior Fossa Society in their consensus statement. It is common concept that midline tumor location, diagnosis of medulloblastoma, younger age at diagnosis, and preoperatively established language impairment should be accepted as the most determinant predisposing conditions for the establishment of this syndrome. A well-recognized pathophysiological explanation of CMS includes disruption of the cerebellar outflow tracts, the cerebellar nuclei, and their efferent projections through the superior cerebellar peduncle. Despite the relative advancement that is recorded regarding the diagnostic section of this disease, no corresponding encouraging results are reported, regarding the available treatment options. On the contrary, it is mainly targeted toward the symptomatic relief of the affected individuals. The basic tenet of our review is centered on the presentation of a report that is dedicated to the definition of CMS etiology, diagnosis, risk factors, clinical presentation, and clinical management. Apart from that, an effort is made that attempts to elucidate the paramount priorities of the scientific forum, which are directed toward the expansion our knowledge in the era of diagnostics, prevention, and therapeutic options for patients suffering from CM, or who are at risk for development of this syndrome. [ABSTRACT FROM AUTHOR]

Purpose: The discussed topic about gadolinium-based contrast agents (GBCA) safety has recently been revived due to the evidence of hyperintensities observed in the dentate nucleus (DN) and globus pallidus (GP) in the brain of patients with normal kidney function. Several preclinical studies have been conducted to understanding how the use of GBCAs can promote the gadolinium deposition in the brain. Here, we evaluate the impact of chronic cerebral hypoperfusion on gadolinium presence.Methods: T1 hyperintensities and BBB integrity were evaluated by MRI in chronically hypoperfused and healthy rats injected with either gadodiamide or hypertonic saline. Additionally, the assessment of glucose metabolism by PET imaging and the gadolinium content by ICP-MS was performed after the last MR scan.Results: Chronically hypoperfused rats displayed a greater MRI T1w signal in the DCN and hippocampus compared to Sham-operated animals, suggesting gadolinium accumulation. Dynamic contrast-enhanced (DCE) MRI assessment of BBB permeability revealed loss of integrity (high Ktrans) after rat injury in the dentate nuclei and hippocampus. Ex vivo tissue analysis showed greater gadolinium retention in the cerebellum and subcortical regions, supporting the imaging finding. FDG-PET imaging of the cerebellum did not reveal abnormal uptake in the DCN after chronic cerebral hypoperfusion.Conclusion: Higher signal intensity followed by higher Gd concentration observed in DCN and hippocampus of animals subjected to cerebral injury can be associated with an increase in BBB permeability due to the applied vascular dementia animal model. Nonetheless, no glucose metabolism abnormalities were detected in chronically hypoperfused cerebellum. [ABSTRACT FROM AUTHOR]

A case of long-term continual self-inflicted penetrating craniocerebral injury to a 59-year-old man with a fatal outcome is reported. The man suffered from paranoid psychosis and alcohol dependence. Over five months, he continually scalped the skin and subcutaneous tissue of his head with a knife until he perforated the skull and dura mater and injured his brain. He eventually sought medical advice, but died after 10 days of hospitalization despite complex conservative treatment. The immediate cause of death was a combination of central nervous system failure and heart failure. The original case presented is sporadic in the forensic literature due to atypical long-term continual self-harm to the head and brain using a sharp object that resulted in perforation of the skull and a fatal outcome. This case also highlights the importance of autopsy to determine the mechanism of injury and cause of death. [ABSTRACT FROM AUTHOR]

The present study investigated the effects of nicorandil on cerebral injury following cardiopulmonary resuscitation (CPR) in a swine model of cardiac arrest. CPR was performed on swine following 4 min induced ventricular fibrillation. Surviving animals were randomly divided into 3 groups: A nicorandil group (n=8), a control group (n=8) and a sham group (n=4). The sham group underwent the same surgical procedure to imitate cardiac arrest, but ventricular fibrillation was not induced. When the earliest observable return of spontaneous circulation (ROSC) was detected, the nicorandil and control groups received injections of nicorandil and saline, respectively. Swine serum was collected at baseline and 5 min, 0.5, 3 and 6 h following ROSC. Serum levels of neuron-specific enolase (NSE), S100β, tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) were measured using ELISA. Animals were euthanized and brain tissue samples were collected and assessed using light and electron microscopy 6 h following ROSC. The expression of aquaporin-4 (AQP-4) in the brain tissue was measured using western blotting. Malondialdehyde (MDA) and glutathione (GSH) levels in the brain tissue were determined using thiobarbituric acid and thiobenzoic acid colorimetric methods, respectively. Serum NSE and S100β were significantly higher in the nicorandil and control groups following CPR, compared with baseline (P<0.05). Additionally, NSE and S100β levels were significantly lower in the nicorandil group compared with the control (P<0.05). Pathological examinations and electron microscopy indicated that nicorandil reduced brain tissue damage. TNF-α and IL-6 levels were significantly decreased in the nicorandil group compared with the control group (P<0.05). Furthermore, AQP-4 expression in brain tissue 6 h following ROSC was significantly lower in the nicorandil group compared with the control group (P<0.05). MDA and GSH levels in swine brain tissue decreased and increased, respectively, in the nicorandil group compared with the control group (P<0.05). The results of the present study demonstrate that nicorandil exerts a protective effect against brain injury following cardiac arrest by reducing oxidative damage, inflammatory responses and brain edema post-ROSC. [ABSTRACT FROM AUTHOR]

Background & aim Overpressure blast-wave induced brain injury (OBI) and its long-term neurological outcome pose significant concerns for military personnel. Our aim is to investigate the mechanism of injury due to OBI. Methods Rats were divided into 3 groups: (1) Control, (2) OBI (exposed 30 psi peak pressure, 2–2.5 ms), (3) Repeated OBI (r-OBI) (three exposures over one-week period). Lung and brain (cortex and cerebellum) tissues were collected at 24 h post injury. Results The neurological examination score was worse in OBI and r-OBI (4.2 ± 0.6 and 3.7 ± 0.5, respectively) versus controls (0.7 ± 0.2). A significant positive correlation between lung and brain edema was found. Malondialdehyde (index for lipid peroxidation), significantly increased in OBI and r-OBI groups in cortex (p < 0.05) and cerebellum (p < 0.01–0.001). The glutathione (endogenous antioxidant) level decreased in cortex (p < 0.01) and cerebellum (p < 0.05) of r-OBI group when compared with the controls. Myeloperoxidase activity indicating neutrophil infiltration, was significantly (p < 0.01–0.05) elevated in r-OBI. Additionally, tissue thromboplastin activity, a coagulation marker, was elevated, indicating a tendency to bleed. NGF and NF-κB proteins along with Iba-1 and GFAP immunoreactivity significantly augmented in the frontal cortex demonstrating microglial activation. Serum biomarkers of injury, NSE, TNF-alpha and leptin, were also elevated. Conclusion OBI triggers both inflammation and oxidative injury in the brain. This data in conjunction with our previous observations suggests that OBI triggers a cascade of events beginning with impaired cerebral vascular function leading to ischemia and chronic neurological consequences. [ABSTRACT FROM AUTHOR]

Background. After perinatal asphyxia, the cerebellum presents more damage than previously suggested. Objectives. To explore if the antioxidant N-acetylcysteine amide (NACA) could reduce cerebellar injury after hypoxia-reoxygenation in a neonatal pig model. Methods. Twenty-four newborn pigs in two intervention groups were exposed to 8% oxygen and hypercapnia, until base excess fell to −20 mmol/l or the mean arterial blood pressure declined to <20 mmHg. After hypoxia, they received either NACA (NACA group, n=12) or saline (vehicle-treated group, n=12). One sham-operated group (n=5) served as a control and was not subjected to hypoxia. Observation time after the end of hypoxia was 9.5 hours. Results. The intranuclear proteolytic activity in Purkinje cells of asphyxiated vehicle-treated pigs was significantly higher than that in sham controls (p=0.03). Treatment with NACA was associated with a trend to decreased intranuclear proteolytic activity (p=0.08), There were significantly less mutations in the mtDNA of the NACA group compared with the vehicle-treated group, 2.0 × 10−4 (±2.0 × 10−4) versus 4.8 × 10−5(±3.6 × 10−4, p<0.05). Conclusion. We found a trend to lower proteolytic activity in the core of Purkinje cells and significantly reduced mutation rate of mtDNA in the NACA group, which may indicate a positive effect of NACA after neonatal hypoxia. Measuring the proteolytic activity in the nucleus of Purkinje cells could be used to assess the effect of different neuroprotective substances after perinatal asphyxia. [ABSTRACT FROM AUTHOR]

Background: Holmes tremor is a rare symptomatic movement disorder, characterized by a combination of resting, postural, and intention tremor. It is usually caused by lesions in the brainstem, thalamus, and cerebellum. Despite pharmacological advances, its treatment remains a challenge; many medications have been used with various degrees of effectiveness. Stereotactic thalamotomy and deep brain stimulation in the ventralis intermedius nucleus have been effective surgical procedures in cases refractory to medical treatment. Case Report: Here we report a young woman with topiramate-responsive Holmes tremor secondary to a brainstem cavernoma. Discussion: Herein we report a Holmes tremor responsive to Topiramate. [ABSTRACT FROM AUTHOR]

Aim: Cerebellar lesions are present in approximately 30% of patients with tuberous sclerosis complex. Although several prior studies have characterized these lesions, our study provides the first description of the specific distribution of these lesions within the cerebellum and the first genotype-phenotype correlation yet to be published.Method: We retrospectively reviewed magnetic resonance images from 220 paediatric and adult patients with tuberous sclerosis complex (95 males, 125 females; mean age 22.7y, range 9mo-81y). Sex, age, and genotype of patients with cerebellar lesions were recorded and specific characteristics, including signal intensity, number, shape, presence of enhancement, calcification or haemorrhage, and location within the cerebellar lobules were noted.Results: Fifty-eight patients (26.4%) had 106 cerebellar lesions (62 right, 44 left). The mean number of cerebellar lesions per patient was 1.8 (range 1-6). Enhancement was present in 42.4% of lesions and folial retraction in 84%. Calcification was detected in 86.8% of lesions. Patients with calcified lesions were older (mean age 21.6y) than patients without calcification (11.5y). TSC2 mutations were detected in 41/42 (97.6%) of patients with cerebellar tubers who had genetic testing and one patient had no mutation identified. None of the patients had TSC1 mutation.Interpretation: We provide new information regarding cerebellar lesions in tuberous sclerosis complex: cerebellar lesions are significantly much more frequent in patients with TSC2 mutations than TSC1 mutations or patients with no mutation identified, and Crus II is the most frequent location of cerebellar lesions. New studies are needed to assess the clinical significance of these lesions. [ABSTRACT FROM AUTHOR]

Online gait corrections are frequently used to restore gait stability and prevent falling. They require shorter response times than voluntary movements which suggests that subcortical pathways contribute to the execution of online gait corrections. To evaluate the potential role of the cerebellum in these pathways we tested the hypotheses that online gait corrections would be less accurate in individuals with focal cerebellar damage than in neurologically intact controls and that this difference would be more pronounced for shorter available response times and for short step gait corrections. We projected virtual stepping stones on an instrumented treadmill while some of the approaching stepping stones were shifted forward or backward, requiring participants to adjust their foot placement. Varying the timing of those shifts allowed us to address the effect of available response time on foot placement error. In agreement with our hypothesis, individuals with focal cerebellar lesions were less accurate in adjusting their foot placement in reaction to suddenly shifted stepping stones than neurologically intact controls. However, the cerebellar lesion group's foot placement error did not increase more with decreasing available response distance or for short step versus long step adjustments compared to the control group. Furthermore, foot placement error for the non-shifting stepping stones was also larger in the cerebellar lesion group as compared to the control group. Consequently, the reduced ability to accurately adjust foot placement during walking in individuals with focal cerebellar lesions appears to be a general movement control deficit, which could contribute to increased fall risk. [ABSTRACT FROM AUTHOR]

Although cerebellar-cortical interactions have been studied extensively in animal models and humans using modern neuroimaging techniques, the effects of cerebellar stroke and focal lesions on cerebral cortical processing remain unknown. In the present study, we analyzed the large-scale functional connectivity at the cortical level by combining high-density electroencephalography (EEG) and source imaging techniques to evaluate and quantify the compensatory reorganization of brain networks after cerebellar damage. The experimental protocol comprised a repetitive finger extension task by 10 patients with unilateral focal cerebellar lesions and 10 matched healthy controls. A graph theoretical approach was used to investigate the functional reorganization of cortical networks. Our patients, compared with controls, exhibited significant differences at global and local topological level of their brain networks. An abnormal rise in small-world network efficiency was observed in the gamma band (30-40 Hz) during execution of the task, paralleled by increased long-range connectivity between cortical hemispheres. Our findings show that a pervasive reorganization of the brain network is associated with cerebellar focal damage and support the idea that the cerebellum boosts or refines cortical functions. Clinically, these results suggest that cortical changes after cerebellar damage are achieved through an increase in the interactions between remote cortical areas and that rehabilitation should aim to reshape functional activation patterns. Future studies should determine whether these hypotheses are limited to motor tasks or if they also apply to cerebro-cerebellar dysfunction in general. [ABSTRACT FROM AUTHOR]

We sought to determine the cerebellar structures responsible for tilt suppression of post-rotatory nystagmus. We investigated ocular motor findings and MRI lesions in 73 patients with isolated cerebellar lesions who underwent recording of the vestibulo-ocular reflex (VOR) using rotatory chair tests. Tilt suppression of post-rotatory nystagmus was diminished in 27 patients (27/73, 37.0 %). The gains of the VOR and the TCs of per- and post-rotatory nystagmus did not differ between the patients with diminished and with normal tilt suppression. The patients with impaired tilt suppression showed perverted ('cross-coupled') head-shaking nystagmus (pHSN) and central positional nystagmus (CPN) more frequently than those with normal responses. Tilt suppression was impaired in five (71.4 %) of the seven patients with isolated nodulus and uvular infarction. Probabilistic lesion-mapping analysis showed that the nodulus and uvula are responsible for tilt suppression. Impaired tilt suppression may be ascribed to disruption of cerebellar contribution to the vestibular velocity-storage mechanism, which integrates information from the semicircular canals and otolith organs to help derive the brain's estimate of the head orientation relative to the pull of gravity. [ABSTRACT FROM AUTHOR]

Background: Myoclonus is a clinical sign characterized by sudden, brief jerky, shock-like involuntary movements of a muscle or group of muscles. Dystonia is defined as a syndrome of sustained muscle contractions, frequently causing twisting and repetitive movements or abnormal postures. Cases of myoclonus or dystonia secondary to a structural lesion in the cerebellum have been reported. However, there has never been a reported case of combined myoclonus and dystonia secondary to a cerebellar lesion. Case presentation: Herein, we report a 22-year-old female patient with sudden-onset myoclonic jerks, dystonic posture and mild ataxia in the right upper extremity. At age 19, she experienced sudden headache with vomiting. The neurological examination showed ataxia, myoclonus and dystonia in the right upper extremity. Brain images demonstrated a hemorrhage in the right cerebellar hemisphere secondary to a cavernous malformation. After resection of the hemorrhagic mass, headache with vomiting disappeared and ataxia improved, but myoclonus and dystonia persisted. Conclusions: It is the first report of combined focal myoclonus and dystonia secondary to a cerebellar lesion. [ABSTRACT FROM AUTHOR]

It is well accepted that the cerebellum plays a crucial role in the prediction of the sensory consequences of movements. Recent findings of altered error processing in patients with selective cerebellar lesions led to the hypothesis that feedback processing and feedback-based learning might be affected by cerebellar damage as well. Thus, the present study investigated learning from and processing of positive and negative feedback in 12 patients with selective cerebellar lesions and healthy control subjects. Participants performed a monetary feedback learning task. The processing of positive and negative feedback was assessed by means of event-related potentials (ERPs) during the learning task and during a separate task in which the frequencies of positive and negative feedback were balanced. Patients did not show a general learning deficit compared to controls. Relative to the control group, however, patients with cerebellar lesions showed significantly higher ERP difference wave amplitudes (rewards-losses) in a time window between 250 and 450 ms after feedback presentation, possibly indicating impaired outcome prediction. The analysis of the original waveforms suggested that patients and controls primarily differed in their pattern of feedback-related negativity and P300 amplitudes. Our results add to recent findings on altered performance monitoring associated with cerebellar damage and demonstrate, for the first time, alterations of feedback processing in patients with cerebellar damage. Unaffected learning performance appears to suggest that chronic cerebellar lesions can be compensated in behaviour. [ABSTRACT FROM AUTHOR]

Human cerebellar lesion studies provide good evidence that the cerebellum contributes to the acquisition of classically conditioned eyeblink responses (CRs). As yet, only one study used more advanced methods of lesion-symptom (or lesion-behavior) mapping to investigate which cerebellar areas are involved in CR acquisition in humans. Likewise, comparatively few studies investigated the contribution of the human cerebellum to CR extinction and savings. In this present study, young adults with focal cerebellar disease were tested. A subset of participants was expected to acquire enough conditioned responses to allow the investigation of extinction and saving effects. 19 participants with chronic surgical lesions of the cerebellum and 19 matched control subjects were tested. In all cerebellar subjects benign tumors of the cerebellum had been surgically removed. Eyeblink conditioning was performed using a standard short delay protocol. An initial unpaired control phase was followed by an acquisition phase, an extinction phase and a subsequent reacquisition phase. Structural 3T magnetic resonance images of the brain were acquired on the day of testing. Cerebellar lesions were normalized using methods optimized for the cerebellum. Subtraction analysis and Liebermeister tests were used to perform lesion-symptom mapping. As expected, CR acquisition was significantly reduced in cerebellar subjects compared to controls. Reduced CR acquisition was significantly more likely in participants with lesions of lobule VI and Crus I extending into Crus II (p<0.05, Liebermeister test). Cerebellar subjects could be subdivided into two groups: a smaller group (n=5) which showed acquisition, extinction and savings within the normal range; and a larger group (n=14) which did not show acquisition. In the latter, no conclusions on extinction or savings could be drawn. Previous findings were confirmed that circumscribed areas in lobule VI and Crus I are of major importance in CR acquisition. In addition, the present data suggest that if the critical regions of the cerebellar cortex are lesioned, the ability to acquire CRs is not only reduced but abolished. Subjects with lesions outside these critical areas, on the other hand show preserved acquisition, extinction and saving effects. As a consequence, studies in human subjects with cerebellar lesions do not allow drawing conclusions on CR extinction and savings. In light of the present findings, previous reports of reduced extinction in humans with circumscribed cerebellar disease need to be critically reevaluated. [ABSTRACT FROM AUTHOR]

Cerebellar stroke is a rare condition with very nonspecific clinical features. The symptoms in the acute phase could imitate acute peripheral vestibular disorders or a brainstem lesion. The aim of this study was to assess the usefulness of the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification in cerebellar stroke and the impact of clinical features on the prognosis. We retrospectively analyzed 107 patients with diagnosed ischemic cerebellar infarction. We studied the clinical features and compared them based on the location of the ischemic lesion and its distribution in the posterior interior cerebellar artery (PICA), superior cerebellar artery (SCA), and anterior inferior cerebellar artery (AICA) territories. According to the TOAST classification, stroke was more prevalent in atrial fibrillation (26/107) and when the lesion was in the PICA territory (39/107). Pyramidal signs occurred in 29/107 of patients and were more prevalent when the lesion was distributed in more than two vascular regions ( p = 0.00640). Mortality was higher among patients with ischemic lesion caused by cardiac sources ( p = 0.00094) and with pyramidal signs ( p = 0.00640). The TOAST classification is less useful in assessing supratentorial ischemic infarcts. Cardioembolic etiology, location of the ischemic lesion, and pyramidal signs support a negative prognosis. [ABSTRACT FROM AUTHOR]

This case series assesses white matter microstructure of the cerebellar peduncles in 4 adolescents born preterm with enlarged ventricles and reduced white matter volume in the cerebrum but no apparent injury to the cerebellum. Subjects (ages 12-17 years, gestational age 26-32 weeks, birth weight 825-2211 g) were compared to a normative sample of 19 full-term controls (9-17 years, mean gestational age 39 weeks, mean birth weight 3154 g). Tract profiles for each of the cerebellar peduncles were generated by calculating fractional anisotropy at 30 points along the central portion of each tract. One or more case subjects exhibited higher fractional anisotropy beyond the 90th percentile in the inferior, middle, and superior cerebellar peduncles. Findings demonstrate that differences in cerebellar white matter microstructure can be detected in the absence of macrostructural cerebellar abnormalities. [ABSTRACT FROM AUTHOR]

Lifestyle modifications, such as physical exercise and dietary supplements, are recommended as protective measures against some neurological disorders. We examined the effects of regular exercise combined with curcumin supplementation against lead-induced oxidative damage of the cerebellum in male rats. Experimental animals ( n = 50) were randomly divided into five groups. Lead acetate (20 mg/kg) was i.p. administered to three groups (except sham and control ones), while the sham group received ethyl oleate (30 mg/kg) three times per week. The curcumin and curcumin+exercise groups received curcumin (30 mg/kg) i.p. five times per week for eight weeks. The exercise program consisted of progressive running on a treadmill (speed from 15 to 22 m/min, 25 to 64 min per day, five times per week for eight weeks). Two days after the last application, the rats were euthanized; their cerebellum was removed and homogenized to measure the levels of brain-derived neurotrophic factor (BDNF) and thiobarbituric acid-reactive substances (TBARSs). Chronic administration of lead significantly increased the cerebellar TBARS levels but did not alter considerably the BDNF levels. Curcumin and curcumin+exercise treatments significantly lowered the cerebellar TBARS levels; a significant increase in the BDNF level was observed in the cerebellum of rats treated with combined intervention. Thus, regular exercise combined with curcumin supplementation may exert a significant neuroprotective effect against lead-induced cerebellar injury by attenuating oxidative stress and improving the brain state through an increase in the BDNF amount. [ABSTRACT FROM AUTHOR]

The aim of the study was to analyze the effect of Ginsenoside Rg1 (Rg1) on cerebral and cerebellar injury in experimental obstructive jaundice (OJ). OJ was done by ligature and section of extrahepatic biliary duct. Rg1 was injected intraperitoneally (10 mg kg −1 d −1 or 20 mg kg −1 d −1 ). Comparison of serum total bile salts (TBA), total bilirubin (TBil), direct bilirubin (DBil), TNF-α, IL-6 and IL-1β among groups. Malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined, also apoptosis and mRNA and protein levels of TIPE2 (TNF-α-inducible protein 8-like 2) were tested in cerebrum and cerebellum. Our results showed that Rg1 reduced MDA and apoptosis in cerebrum and cerebellum induced by OJ, also GSH and antioxidant enzyme activity were raised obviously in rats treated with Rg1. Moreover, decreased mRNA and protein levels of TIPE2 in OJ rats and Rg1 could improve the decreased mRNA and protein levels of TIPE2 in OJ rats. In conclusion, Rg1 decreased oxidative stress and apoptosis, also recovered the antioxidant status and mRNA and protein levels of TIPE2 in the cerebrum and cerebellum of OJ rats. [ABSTRACT FROM AUTHOR]

Vertigo is a common symptom in everyday clinical practice. The treatment depends on the specific etiology. Vertigo may be secondary to inner ear pathology, or any existing brainstem or cerebellar lesion but may also be psychogenic. Central vertigo is a consequence of a central nervous system lesion. It is often associated with a focal neurological deficit. Peripheral vertigo is secondary to dysfunction of the peripheral vestibular system and is usually characterized by an acute vertigo with loss of balance, sensation of spinning in the space or around self, and is exaggerated with changes of the head and body position; no other neurological deficit is present. Some medications may also cause vertigo. Depending on the cause of the vertigo, drugs with different mechanisms of action, physical therapy, psychotherapy, as well as surgery may be used to combat this disabling malady. Symptomatic treatment has a particularly important role, regardless of the etiology of vertigo. We reviewed the current medications recommended for patients with vertigo, their mechanisms of action and their most frequent side effects. [ABSTRACT FROM AUTHOR]

Increasing evidence indicates that dexmedetomidine (DEX), a selective α2-adrenergic receptor agonist, has a neuroprotective effect against cerebral injury. However, it remains unknown whether and how DEX functionally prevents the pathological form of synaptic plasticity caused by ischemia in the hippocampal CA1 neurons. To address this issue, we analyzed the role of DEX using a model of brain ischemia (oxygen and glucose deprivation, OGD) referred to as post-ischemic LTP (i-LTP). We found that DEX could reduce i-LTP by selectively activating α2 receptors. To clarify its detailed mechanisms, the presynaptic and postsynaptic roles of DEX were investigated. The activation of the α2 receptors of DEX decreased the frequency spontaneous mEPSCs, which exerted its presynaptic mechanisms. In addition, DEX also decreased the amplitude of mEPSCs and prevented the depolarization of postsynaptic membranes during OGD treatment, which exerted its postsynaptic mechanisms. More importantly, our results indicate that postsynaptic β receptors, not α1 receptors, participated in i-LTP. Therefore, these results demonstrated that decreasing β receptors activation by DEX-medicated pre- and post-synaptic α2 receptors activation is responsible for i-LTP. Because of the NMDARs required for i-LTP, we further examined the critical roles of postsynaptic β receptors downstream PKA regulation of NMDA receptor-mediated EPSCs (NMDA EPSC). We clarified that it is attributable to the direct effect of DEX on NMDA EPSC as mediated by PKA inactivation. These findings suggest that DEX can protect neurons from functional damage caused by a relatively mild degree of transient cerebral ischemia, and this effect is mediated by both presynaptic reduction of NE and glutamate release and postsynaptic suppression of NMDAR activation by β receptors and downstream PKA regulation. [ABSTRACT FROM AUTHOR]

Aim Cerebellar injury is a characteristic injury associated with preterm infants. However, the impact of cerebellar injury on the development of preterm infants is unclear. Method We reviewed magnetic resonance image studies of preterm infants with cerebral palsy retrospectively and evaluated the developmental outcomes. Results Cerebellar injury was recognized in 9 (2.4%) of 381 patients with cerebral palsy who were born preterm. The median gestational age was 26 (range 23–32) weeks and the median birth weight was 938 (range 492–1450) g. Seven of the nine patients had severe symmetric injuries to the inferior cerebellar hemispheres, resulting in a pancake-like appearance of the residual upper cerebellum. Supratentorial lesions were also recognized: periventricular leukomalacia in seven; atrophy of the basal ganglia in two; and intraventricular hemorrhage in two. Importantly, the motor dysfunction was related to the reduction in the white matter volume and severity of basal ganglia atrophy, but not to the cerebellar injury. Four of the nine patients could walk without limitations despite extensive cerebellar disruption. Only four patients could speak meaningful words during the study and only one spoke two-word sentences. Interpretation The patients with cerebellar injury might have a communication handicap, rather than altered motor function. Prematurity-related cerebellar complications require more attention in terms of cognitive and speech function, in addition to neuromotor development. [ABSTRACT FROM AUTHOR]

Phytanic acid (Phyt) accumulates in various peroxisomal diseases including Refsum disease (RD) and Zellweger syndrome (ZS). Since the pathogenesis of the neurological symptoms and especially the cerebellar abnormalities in these disorders are poorly known, we investigated the effects of in vivo intracerebral administration of Phyt on a large spectrum of redox homeostasis parameters in the cerebellum of young rats. Malondialdehyde (MDA) levels, sulfhydryl oxidation, carbonyl content, nitrite and nitrate concentrations, 2′,7′-dichlorofluorescein (DCFH) oxidation, total (tGS) and reduced glutathione (GSH) levels and the activities of important antioxidant enzymes were determined at different periods after Phyt administration. Immunohistochemical analysis was also carried out in the cerebellum. Phyt significantly increased MDA and nitric oxide (NO) production and decreased GSH levels, without altering tGS, DCFH oxidation, sulfhydryl oxidation, carbonyl content and the activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PD). Furthermore, immunohistochemical analysis revealed that Phyt caused astrogliosis and protein nitrosative damage in the cerebellum. It was also observed that the NO synthase inhibitor N ω -Nitro-L-arginine methyl ester (L-NAME) prevented the increase of MDA and NO production as well as the decrease of GSH and the immunohistochemical alterations caused by Phyt, strongly suggesting that reactive nitrogen species (RNS) were involved in these effects. The present data provide in vivo solid evidence that Phyt disrupts redox homeostasis and causes astrogliosis in rat cerebellum probably mediated by RNS production. It is therefore presumed that disequilibrium of redox status may contribute at least in part to the cerebellum alterations characteristic of patients affected by RD and other disorders with Phyt accumulation. [ABSTRACT FROM AUTHOR]

Objectives To elucidate the prevalence of cerebellar injury and its relationship to functional outcomes in preterm children with cerebral palsy (CP) after intraventricular hemorrhage (IVH). Participants We selected 69 children (40 males and 29 females, aged between 6 and 13 years) out of 2049 with cerebral palsy who visited Morinomiya Hospital, the regional center hospital for CP in West Japan. The inclusion criteria were (1) gestational age under 36 weeks at birth, (2) clear history of postnatal intraventricular hemorrhage, and (3) age at investigation over 6 years old. Those without sufficient imaging study or functional evaluation were excluded. Methods The participants were divided into four groups according to the presence of post-hemorrhagic hydrocephalus (PH) and cerebellar injury (CI): PH+/CI+, PH+/CI−, PH−/CI+, and PH−/CI−. Type of CP, ability to walk, verbal function, the incidence of severe visual impairment, and the complication of epilepsy were investigated and compared among the groups. Results The gestational ages of the participants were between 22 and 34 weeks, and their birth weight was between 412 and 1788 g. PH and CI were found in 39 (57%) and 40 (58%) children, respectively. Both the PH+/CI+ group ( n = 31) and the PH−/CI+ group ( n = 9) showed significantly lower walking and verbal abilities and a higher incidence of epilepsy than the PH−/CI− group ( n = 21), while the PH+/CI− group showed no significant difference from the PH−/CI− group. Severe visual impairment was found only in the PH+/CI+ group and the PH−/CI+ group. Conclusions The prevalence of CI in preterm children with CP after IVH (58%) was almost the same as that of PH. CI is one of the most significant complications in preterm infants, affecting motor and verbal functions and being associated with epilepsy more than PH. [ABSTRACT FROM AUTHOR]

Several rodent models with spontaneous mutations causing cerebellar pathology are impaired in motor functions during the neonatal period, including Grid2 Lc , Rora sg , Dab1 scm , Girk2 Wv , Lmx1a dr-sst , Myo5a dn , Inpp4a wbl , and Cacna1a rol mice as well as shaker and dystonic rats. Deficits are also evident in murine null mutants such as Zic1 , Fgfr1 / FgFr2 , and Xpa / Ercc8 . Behavioral deficits are time-dependent following X-irradiated- or aspiration-induced lesions of the cerebellum in rats. In addition, motor functions are deficient after lesions in cerebellar-related pathways. As in animal subjects, sensorimotor disturbances have been described in children with cerebellar lesions. These results underline the importance of the cerebellum and its connections in the development of motor functions. [ABSTRACT FROM AUTHOR]

Cerebellar injury is increasingly recognized as an important complication of very preterm birth. However, the neurodevelopmental consequences of early life cerebellar injury in prematurely born infants have not been well elucidated. We performed a literature search of studies published between 1997 and 2014 describing neurodevelopmental outcomes of preterm infants following direct cerebellar injury or indirect cerebellar injury/underdevelopment. Available data suggests that both direct and indirect mechanisms of cerebellar injury appear to stunt cerebellar growth and adversely affect neurodevelopment. This review also provides important insights into the highly integrated cerebral-cerebellar structural and functional correlates. Finally, this review highlights that early life impairment of cerebellar growth extends far beyond motor impairments and plays a critical, previously underrecognized role in the long-term cognitive, behavioral, and social deficits associated with brain injury among premature infants. These data point to a developmental form of the cerebellar cognitive affective syndrome previously described in adults. Longitudinal prospective studies using serial advanced magnetic resonance imaging techniques are needed to better delineate the full extent of the role of prematurity-related cerebellar injury and topography in the genesis of cognitive, social-behavioral dysfunction. [ABSTRACT FROM AUTHOR]

Background: The mechanical characterization of infant porcine cerebellum tissue in tension at high strain rate is crucial for modeling traumatic cerebellum injury, which is in turn helpful for understanding the biomechanics of such injuries suffered in traffic accidents. Material and Method: In this study, the infant porcine cerebellum tissue was given three loading velocities, ie, 2s-1, 20s-1 and 100s-1 with up to 30% strain to investigate the tensile properties. At least six tensile tests for each strain rate were validly performed. Fung, Gent, Ogden and exponential models were applied to fit the constitutive equations, so as to obtain material parameters from the experimental data. Results: The Lagrange stress of infant porcine cerebellum tissue in tension appeared to be no more than 3000Pa at each loading velocity. More specifically, the Lagrange stress at 30% strain was (393.7±84.4)Pa, (928.3±56.3)Pa and (2582.4±282.2)Pa at strain rates of 2s-1, 20s-1 and 100s-1, respectively. Fung (0.833≤R2≤0.924), Gent (0.797≤R2≤0.875), Ogden (0.859≤R2≤0.944) and exponential (0.930≤R2≤0.972) models provided excellent fitting to experimental data up to 30% strain. Conclusions: The infant cerebellum tissue shows a stiffer response with increase of the loading speed, indicating a strong strain-rate sensitivity. This study will enrich the knowledge on the material properties of infant brain tissue, which may augment the biofidelity of finite element model of human pediatric cerebellum. [ABSTRACT FROM AUTHOR]

Previous research in patients with cerebellar damage suggests that the cerebellum plays a role in covert visual attention. One limitation of some of these studies is that they examined patients with heterogeneous cerebellar damage. As a result, the patterns of reported deficits have been inconsistent. In the current study, we used functional neuroimaging (fMRI) in healthy adults ( N =14) to examine whether or not the cerebellum plays a role in covert visual attention. Participants performed two covert attention tasks in which they were cued exogenously (with peripheral flashes) or endogenously (using directional arrows) to attend to marked locations in the visual periphery without moving their eyes. We compared BOLD activation in these covert attention conditions to a number of control conditions including: the same attention tasks with eye movements, a target detection task with no cueing, and a self-paced button-press task. Subtracting these control conditions from the covert attention conditions allowed us to effectively remove the contribution of the cerebellum to motor output. In addition to the usual fronto-parietal networks commonly engaged by these attention tasks, lobule VI of the vermis in the cerebellum was also activated when participants performed the covert attention tasks with or without eye movements. Interestingly, this effect was larger for exogenous compared to endogenous cueing. These results, in concert with recent patient studies, provide independent yet converging evidence that the same cerebellar structures that are involved in eye movements are also involved in visuospatial attention. [ABSTRACT FROM AUTHOR]

The cerebellum applies an internal forward-model to predict the sensory consequences of actions. This forward-model is updated based on on-line performance monitoring. A previous study has shown that performance monitoring is altered in patients with focal vascular cerebellar lesions, but altered neural responses are not paralleled by impaired behaviour, and the critical cerebellar sites have yet to be identified. The present study investigated if saccadic performance monitoring is more severely altered in patients with cerebellar degenerative disease relative to the previously examined patients with focal vascular cerebellar lesions, and which cerebellar regions support performance monitoring. 16 patients and 16 healthy controls performed an antisaccade task while an electroencephalogram (EEG) was recorded. Error rates were increased, and the error-related negativity (ERN), an event-related potential (ERP) component associated with error processing/performance monitoring, was reduced while the error positivity (Pe), a later ERP component related to more conscious aspects of error processing, was preserved in patients. Thus, performance monitoring is altered in patients with cerebellar degeneration, confirming a critical role of the cerebellum for fast classification of saccadic accuracy. In contrast to patients with focal lesions, post-acute functional reorganization and compensation presumably is hampered by disease progression, resulting in altered neural processing and impaired behavioural performance. Voxel-based morphometry (VBM) indicated the strongest effects for behavioural performance, with correlations between gray matter volume reduction in bilateral posterolateral regions (left Crus II and right lobule VI) and increased error rates. Moreover, somewhat smaller correlations were found for volume loss in left lobule VIIb/VIIIa and right lobule V and ERN amplitude, and in right Crus I and Pe amplitude. The present findings are consistent with involvement of posterolateral cerebellar regions in motor and cognitive functions. [ABSTRACT FROM AUTHOR]

Perihaematomal oedema (PHO) is an important pathophysiological marker of secondary injury in intracerebral haemorrhage (ICH). In this Review, we describe a novel method to conceptualize PHO formation within the framework of Starling's principle of movement of fluid across a capillary wall. We consider progression of PHO through three stages, characterized by ionic oedema (stage 1) and progressive vasogenic oedema (stages 2 and 3). In this context, possible modifiers of PHO volume and their value in identifying patients who would benefit from therapies that target secondary injury are discussed; the practicalities of using neuroimaging to measure PHO volume are also considered. We examine whether PHO can be used as a predictor of neurological outcome following ICH, and we provide an overview of emerging therapies. Our discussion emphasizes that PHO has clinical relevance both as a therapeutic target, owing to its augmentation of the mass effect of a haemorrhage, and as a surrogate marker for novel interventions that target secondary injury. [ABSTRACT FROM AUTHOR]

We live in a dynamic and changing environment, which necessitates that we adapt to and efficiently respond to changes of stimulus form ('what') and stimulus occurrence ('when'). Consequently, behaviour is optimal when we can anticipate both the 'what' and 'when' dimensions of a stimulus. For example, to perceive a temporally expected stimulus, a listener needs to establish a fairly precise internal representation of its external temporal structure, a function ascribed to classical sensorimotor areas such as the cerebellum. Here we investigated how patients with cerebellar lesions and healthy matched controls exploit temporal regularity during auditory deviance processing. We expected modulations of the N2b and P3b components of the event-related potential in response to deviant tones, and also a stronger P3b response when deviant tones are embedded in temporally regular compared to irregular tone sequences. We further tested to what degree structural damage to the cerebellar temporal processing system affects the N2b and P3b responses associated with voluntary attention to change detection and the predictive adaptation of a mental model of the environment, respectively. Results revealed that healthy controls and cerebellar patients display an increased N2b response to deviant tones independent of temporal context. However, while healthy controls showed the expected enhanced P3b response to deviant tones in temporally regular sequences, the P3b response in cerebellar patients was significantly smaller in these sequences. The current data provide evidence that structural damage to the cerebellum affects the predictive adaptation to the temporal structure of events and the updating of a mental model of the environment under voluntary attention. [ABSTRACT FROM AUTHOR]

The vulnerability of the fetal and newborn brain to events in utero or at birth that cause damage arising from perturbations of cerebral blood flow and metabolism, such as the accumulation of free radicals and excitatory transmitters to neurotoxic levels, has received considerable attention over the last few decades. Attention has usually been on the damage to cerebral structures, particularly, periventricular white matter. The rapid growth of the cerebellum in the latter half of fetal life in species with long gestations, such as the human and sheep, suggests that this may be a particularly important time for the development of cerebellar structure and function. In this short review, we summarize data from recent studies with fetal sheep showing that the developing cerebellum is particularly sensitive to infectious processes, chronic hypoxia and asphyxia. The data demonstrates that the cerebellum should be further studied in insults of this nature as it responds differently to the remainder of the brain. Damage to this region of the brain has implications not only for the development of motor control and posture, but also for higher cognitive processes and the subsequent development of complex behaviours, such as learning, memory and attention. [ABSTRACT FROM AUTHOR]

In contrast to other astroglial populations, Bergmann glia (BG) form a strictly arranged system where each cell contacts the pia, with an architecture and function resembling that of immature radial glia. As a consequence, a post- lesion glial reaction is expected to differ from that observed in other parts of the brain. The present study describes the characteristic phases of intermediate filament protein formation during the different stages of BG response following injury and compares them with reactive glial patterns of other brain areas and patterns of glial development. The progress of Bergmann glial repair shares similar features with glial development. Following injury, BG developed nestin immunopositivity; then, colocalization of nestin and GFAP was observed. Finally, exclusively GFAP-immunopositive BG were restituted, denser, and thicker than before. The changes of intermediate filament composition appeared at first at the proximal and distal ends of BG fibers, i.e., at the perikaryal 'root' and in the pial endfeet. No astrocytic invasion was present in the molecular layer, nor any distinct rearrangement of BG. These results demonstrate the role of the resident glia in glial reactions and refer to the priority of gliomeningeal connections. [ABSTRACT FROM AUTHOR]

In this study we examined cerebellar alterations in a neonatal rat model of hypoxic-ischemic brain injury with or without hypoxic preconditioning (Pc). Between postnatal days 7 and 15, the cerebellum is still undergoing intense cellular proliferation, differentiation and migration, dendritogenesis and synaptogenesis. The expression of glutamate decarboxylase 1 (GAD67) and the differentiation factor NeuroD1 were examined as markers of Purkinje and granule cells, respectively. We applied quantitative immunohistochemistry to sagittal cerebellar slices, and Western blot analysis of whole cerebella obtained from control (C) rats and rats submitted to Pc, hypoxia-ischemia (L) and a combination of both treatments (PcL). We found that either hypoxia-ischemia or Pc perturbed the granule cells in the posterior lobes, affecting their migration and final placement in the internal granular layer. These effects were partially attenuated when the Pc was delivered prior to the hypoxia-ischemia. Interestingly, whole nuclear NeuroD1 levels in Pc animals were comparable to those in the C rats. However, a subset of Purkinje cells that were severely affected by the hypoxic-ischemic insult—showing signs of neuronal distress at the levels of the nucleus, cytoplasm and dendritic arborization—were not protected by Pc. A monoclonal antibody specific for GAD67 revealed a three-band pattern in cytoplasmic extracts from whole P15 cerebella. A ∼110 kDa band, interpreted as a potential homodimer of a truncated form of GAD67, was reduced in Pc and L groups while its levels were close to the control animals in PcL rats. Additionally we demonstrated differential glial responses depending on the treatment, including astrogliosis in hypoxiated cerebella and a selective effect of hypoxia-ischemia on the vimentin-immunolabeled intermediate filaments of the Bergmann glia. Thus, while both glutamatergic and GABAergic cerebellar neurons are compromised by the hypoxic-ischemic insult, the former are protected by a preconditioning hypoxia while the latter are not. [ABSTRACT FROM AUTHOR]

A growing literature points to a specific role of the cerebellum in affect processing. However, understanding of affect processing disturbances following discrete cerebellar lesions is limited. We administered the Tübingen Affect Battery to assess recognition of emotional facial expression and emotional prosody in 15 patients with a cerebellar infarction and 10 age-matched controls. On emotional facial expression tasks, patients compared to controls showed impaired selection and matching of facial affect. On prosody tasks, patients showed marked impairments in naming affect and discriminating incongruencies. These deficits were more pronounced for negative affects. Our results confirm a significant role of the cerebellum in processing emotional recognition, a component of social cognition. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the microstructural integrity of superior cerebellar peduncles (SCP) and middle cerebellar peduncles (MCP) by using DTI tractography method, and further to detect whether the microstructural integrity of these major cerebellar pathways is related to motor function in children with diffuse periventricular leucomalacia (PVL) born preterm. Materials and methods: 46 children with diffuse PVL (30 males and 16 females; age range 3–48 months; mean age 22.4±6.7 months; mean gestational age 30.5±2.2 weeks) and 40 healthy controls (27 males and 13 females; age range 3.5–48 months; mean age 22.1±5.8 months) were enrolled in this study. DTI outcome measurements, fractional anisotropy (FA), for the SCP, MCP and cortical spinal tract (CST) were calculated. The gross motor function classification system (GMFCS) was used for assessing motor functions. Results: Compared to the controls, patients with diffuse PVL had a significantly lower FA in bilateral SCP, MCP and CST. There was a significant negative correlation between GMFCS levels and FA in bilateral SCP, MCP and CST in the patients group. In addition, significant inverse correlation of FA value was found between not only the contralateral but also the ipsilateral CST and SCP/MCP. Conclusions: These findings suggest that the injury of SCP and MCP may contribute to the motor dysfunction of diffuse PVL. Moreover, the correlations we found between supratentorial and subtentorial injured white matter extend our knowledge about the cerebro-cerebellar white matter interaction in children with diffuse PVL. [ABSTRACT FROM AUTHOR]

Abstract: Hypoxic–ischemic encephalopathy (HIE) in neonates is a leading cause of neurological impairment. Significant progress has been achieved investigating the pathologic contributions of excitotoxicity, oxidative stress, and neuroinflammation to cerebral injury in HIE. Less extensively investigated has been the contribution of vascular dysfunction, and whether modulation of cerebral perfusion may improve HIE outcome. Here, we investigated the function of the prostaglandin E2 (PGE2) EP4 receptor, a vasoactive Gαs-protein coupled receptor (GPCR), in rodent models of neonatal HIE. The function of PGE2 signaling through the EP4 receptor was investigated using pharmacological and conditional knockout genetic strategies in vivo in rodent models of HIE. Pharmacologic activation of the EP4 receptor with a selective agonist was significantly cerebroprotective both acutely and after 7days. Measurement of cerebral perfusion during and after hypoxia–ischemia demonstrated that EP4 receptor activation improved cerebral perfusion in both the contralateral and ipsilateral hypoxic–ischemic hemispheres. To test whether vascular EP4 signaling exerted a critical function in HIE injury, cell specific conditional knockout mouse pups were generated in which endothelial EP4 receptor was selectively deleted postnatally. VE-Cadherin Cre-ERT2;EP4lox/lox pups demonstrated significant increases in cerebral injury as compared to VE-Cadherin Cre-ERT2;EP4+/+ control littermates, indicating that endothelial EP4 signaling is protective in HIE. Our findings identify vascular PGE2 signaling through its EP4 receptor as protective in HIE. Given the pharmacologic accessibility of endothelial EP4 GPCRs, these data support further investigation into novel approaches to target cerebral perfusion in neonatal HIE. [Copyright &y& Elsevier]

Abstract: Oculodentodigital dysplasia (ODDD) is a rare autosomal dominant disease that results in visible developmental anomalies of the limbs, face, eyes and teeth. Recently analysis of human connexin43 (Cx43) DNA sequences has revealed a number of different missense, duplication and frame shift mutations resulting in this phenotype. A mouse model of this disorder has been created with a missense point mutation of the glycine amino acid at position 60 to serine (G60S). Heterozygote +/G60S mice exhibit a similar ODDD phenotype as observed in humans. In addition to the malformations listed above, ODDD patients often have neurological findings. In the brain, Cx43 is highly expressed in astrocytes and has been shown to play a role in neuroprotection. We were interested in determining the effect of the +/G60S mutation following stroke. Four days after middle cerebral artery occlusion the volume of infarct was larger in mice with the +/G60S mutation. In astrocyte-neuron co-cultures, exposure to glutamate also resulted in greater cellular death in the +/G60S mutants. Protein levels of Cx43 in the mutant mouse were found to be reduced when compared to the normal tissue. Cx43 protein was observed as a continual line of small punctate aggregates in the plasma membrane with increased intracellular localization, which is distinct from the larger plaques seen in the normal mouse astrocytes. Functionally, primary +/G60S astrocytes exhibited reduced gap junctional coupling and increased hemichannel activity, which may underlie the mechanism of increased damage during stroke. This article is part of the Special Issue Section entitled ‘Current Pharmacology of Gap Junction Channels and Hemichannels’. [Copyright &y& Elsevier]

Following unilateral cerebral injury, several patterns of cerebellar metabolism have been noted on positron emission tomography (PET); these changes have been attributed both to the distant diaschisis as well as to reorganizational changes within the cerebellum. We used diffusion tensor magnetic resonance imaging (MRI) to study 14 children who had undergone cerebral hemispherectomy because of intractable epilepsy and compared them with those from 17 controls. In 10 children who had preoperative and postoperative scans, a paired comparison was performed. Our findings showed significantly higher fractional anisotropy values in corticopontocerebellar pathways postoperatively compared to preoperatively. When compared to controls, we found a higher rate of age-related fractional anisotropy changes of corticopontocerebellar pathways in the postoperative scans. Our results indicate reorganizational changes in the contralateral (intact) corticopontocerebellar pathway and the cerebellar white matter. These changes likely contribute to the far better motor outcomes seen in children compared to adults sustaining such cortical injuries. [ABSTRACT FROM PUBLISHER]

We examined the influence of focal cerebellar lesions on working memory (n-back task), gait, and the interaction between working memory and different gait tasks in a dual-task paradigm. The analysis included 17 young patients with chronic focal lesions after cerebellar tumor resection and 17 agematched controls. Patients have shown mild to moderate ataxia. Lesion sites were examined on the basis of structural magnetic resonance imaging. N-back tasks were executed with different levels of difficulty (n = 1-4) during sitting (baseline), treadmill walking, and treadmill tandem walking (dual-task conditions). Patients exhibited decreased n-back performance particularly at difficult n-back levels and in dual-task conditions. Voxel-based lesion-symptom mapping revealed that decreased baseline n-back performance was associated with lesions of the posterolateral cerebellar hemisphere and the dentate nucleus. By contrast, decreased n-back performance in dual-task conditions was more associated with motor-related areas including dorsal portions of the dentate and the interposed nucleus, suggesting a prioritization of the motor task. During baseline walking, increased gait variability was associated with lesions in medial and intermediate regions, whereas for baseline tandem gait, lesions in the posterolateral hemispheres and the dentate nucleus became important. Posterolateral regions overlapped with regions related to baseline n-back performance. Consistently, we observed increased tandem gait variability with growing n-back difficulty in the dual-task condition. These findings suggest that dual-task effects in cerebellar patients are at least partially caused by a common involvement of posterolateral cerebellar regions in working memory and complex motor tasks. [ABSTRACT FROM AUTHOR]

Little is known about the effects of blast exposure on the human brain in the absence of head impact. Clinical reports, experimental animal studies, and computational modeling of blast exposure have suggested effects on the cerebellum and brainstem. In US military personnel with isolated, primary blast-related ‘mild’ traumatic brain injury and no other known insult, we found diffusion tensor MRI abnormalities consistent with cerebellar white matter injury in 3 of 4 subjects. No abnormalities in other brain regions were detected. These findings add to the evidence supporting the hypothesis that primary blast exposure contributes to brain injury in the absence of head impact and that the cerebellum may be particularly vulnerable. However, the clinical effects of these abnormalities cannot be determined with certainty; none of the subjects had ataxia or other detected evidence of cerebellar dysfunction. The details of the blast events themselves cannot be disclosed at this time, thus additional animal and computational modeling will be required to dissect the mechanisms underlying primary blast-related traumatic brain injury. Furthermore, the effects of possible subconcussive impacts and other military-related exposures cannot be determined from the data presented. Thus many aspects of topic will require further investigation. [ABSTRACT FROM AUTHOR]

Abstract: The involvement of the cerebellum in unfavorable outcomes of extreme prematurity is increasingly recognized. Evidence implicates both cerebellar injury and cerebellar growth failure, which, along with supratentorial lesions, aggravate motor and developmental outcomes. We describe clinical and neuroradiologic findings of 12 extremely premature patients with acquired pontocerebellar hypoplasia (mean follow-up, 4 years). Patients’ neuromotor outcomes involved combined motor abnormalities (spasticity, dystonia, and ataxia), whereas 25% were ambulatory by age 4 years. All patients exhibited developmental delays of variable degrees. One patient died at age 7.5 years. The possible etiopathogenesis, presentations, sequelae, and differential diagnoses of acquired pontocerebellar hypoplasia are discussed. [Copyright &y& Elsevier]

Opsoclonus-myoclonus may be caused by various neurological conditions and toxic-metabolic states, but typically occurs as a parainfectious or paraneoplastic manifestation. The development of opsoclonus-myoclonus has been variably attributed to lesions in the pons or cerebellum. Herein the authors describe a case of opsoclonus-myoclonus due to posterior reversible encephalopathy syndrome in which magnetic resonance imaging revealed lesions in the region of the cerebellar dentate nuclei. Clinical and radiological resolution of the opsoclonus-myoclonus and of the posterior reversible encephalopathy syndrome followed antihypertensive therapy. [ABSTRACT FROM AUTHOR]

The article discusses the results of a study that compared the incidence and risk factors for cerebral injury in twin-twin transfusion syndrome in monochorionic and dichorionic twins treated with fetoscopic laser surgery. The study showed that gestational age at birth was independently associated with increased risk for cerebral injury. It concludes that cerebral injury in twins with twin-twin transfusion syndrome occurs antenatally in contrast to dichorionic twins.

Summary: Traditionally, the cerebellum has been regarded as a central component of the motor system. Recent studies suggest an important role played by the cerebellum in the development of cognitive and social functions. The objective of this study was to evaluate the incidence of cerebellar injury and to define the obstetrical, neonatal, and radiologic characteristics, as well as the functional outcomes in a population of very preterm infants. Methods: This retrospective study included neonates born before 30 weeks of gestational age between March 2004 and July 2007. Infants underwent MRI studies at a term-adjusted age; for each preterm infant with cerebellar injury, we identified two infants for the control group with normal MRI, matched on the basis of gestational age. We collected pertinent demographic, prenatal, and acute postnatal data for all infants. Follow-up assessment was performed at 2 years, using the Brunet-Lezine scale. Results: A total of 148 ex-preterm infants were studied. Cerebellar injury was present in 14 (9 %) cases and associated with supratentorial parenchymal injury in 90 %. Duration of ventilation was longer in children with cerebellar injury, compared to controls (19.5 days vs 16.5 days; P =0.03). The other neonatal criteria analyzed were comparable between the two groups. Global developmental, functional, and social-behavioral deficits were more common and profound in preterm infants with cerebellar injury, with no significant difference. Conclusion: This study confirms the high incidence of cerebellar injury in very preterm infants and the importance of a specific neurobehavioral follow-up. [Copyright &y& Elsevier]

Intracerebral hemorrhage (ICH) is a major public-health problem worldwide. No proven treatments are available for this condition, which is associated with high rates of morbidity and mortality. Only 20% of individuals who survive ICH are independent at 6 months. Hypertension, cerebral amyloid angiopathy (CAA) and anticoagulation are known to be associated with such hemorrhages. No effective preventive therapies exist specifically for CAA-related ICH. The incidence of hypertension-related ICH might be decreasing in some populations with improvements in the treatment of hypertension; however, the incidence of anticoagulant-related ICH is increasing, as the use of anticoagulants rises. Many questions remain unanswered regarding the clinical management of ICH, although in the past 10 years completed medical and surgical clinical trials-examining hemostatic therapy, blood pressure control and/or hematoma evacuation-have refined our understanding of the goals of such management. Ongoing clinical trials, which have built on the lessons of past studies, hold promise for the development of effective, scientifically proven treatments for ICH. In this Review, we discuss clinical trials for ICH that have been completed in the past 10 years, the contributions of these studies to the clinical management of ICH, and the ongoing trials that might further improve clinical care. [ABSTRACT FROM AUTHOR]

The article presents abstracts of studies to be presented at the 64th Annual Meeting of the American Academy for Cerebral Palsy and Developmental Medicine (AACPDM), including "Development of the Child's Challenging Behaviour Scale," by H. M. Bourke-Taylor et al, "Prevalence of autism spectrum disorders in ex-preterm survivors of cerebellar injury," by C. Limperopoulos et al, and "Functional outcomes in Rett syndrome," by F. S. Fidcock et al.

The article discusses a study which presented an analysis of the local synaptic reorganizations occurring along Purkinje cell dendrites after cerebellar injury. Topics covered include how the distribution of excitatory parallel fiber and climbing fiber synapses changed along the dendritic arbor of Purkinje cells following the removal of a subset of parallel fiber innervation and cerebellar synaptic physiology.

Transient cortical blindness is reported to occur in 0.3% to 1% of cerebral angiography procedures. It develops within minutes of contrast medium injection and lasts for up to several days. We report a long episode of transient cortical blindness in a 17-year-old boy with cerebellar haemangioblastoma, which started during the preoperative vertebral angiography and lasted for 5 days. CT performed 2 days after the sudden onset of bilateral visual loss showed multiple asymmetrical lesions within the brain parenchyma in the distribution of the posterior cerebral circulation. Even though the patient’s vision was completely restored 5 days after angiography, repeat MRI performed 2 months after angiography showed improvement but with residual lesions in the thalami, cerebellum and occipital lobe. [ABSTRACT FROM AUTHOR]

Abstract: Injury to the cerebellum and brainstem is becoming increasingly recognized in prematurely born infants. The role of infection/inflammation in mediating damage to those structures in the preterm brain is largely unknown. Preterm fetal sheep (70% gestation) received either saline-vehicle (control group; n=11) or Escherichia coli lipopolysaccharide (100 ng intravenous [i.v.]; lipopolysaccharide [LPS] group; n=9), and were allowed to recover for 3 days before sacrifice. A diffuse pattern of cerebellar white matter damage was observed in all animals exposed to LPS, while focal cerebellar white matter lesions were observed in three out of nine animals, and an intragyral white matter hemorrhage in one animal. Cerebellar white matter injury was associated with a statistically significant loss of oligodendrocyte transcription factor-2–positive oligodendrocytes and increased terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling–positive cell counts. Ionized calcium binding adapter molecule 1 (Iba1)–positive cells which had the morphology of activated microglia were commonly observed in areas of injury. There was no obvious injury to the cerebellar cortex or to cerebellar Purkinje cells, and no obvious injury in any region of the brainstem. These data provide support for a role of infection/inflammation in selective white matter injury in the immature cerebellum, and demonstrate a differential vulnerability of the brainstem and cerebellar white matter to injury at this time. [Copyright &y& Elsevier]