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Infection resulting from Plasmodium vivax is the commonest type found in India as well as other tropical regions. The clini­cal picture is variable depending on the nature, immunity of the child, and lives in an endemic area or not. Here, we report a child, who presented with cerebellar dysfunction with intact sensorium and Plasmodium vivax was positive on peripheral smear.

The article describes the case of an 18-year-old male college student who suddenly developed a severe occipital headache while lifting weights. The patient underwent emergent tracheal intubation for airway protection. He had a ruptured cerebellar arteriovenous malformation (AVM) and a large hematoma, but he fully recovered on non-surgical management.

Abstract: Cerebellar glioblastoma multiforme (GBM) occurs rarely in adults, accounting for 0.4–3.4% of all GBM. Current studies have all involved small patient numbers, limiting the clear identification of prognostic factors. Additionally, while few studies have compared cerebellar GBM to their supratentorial counterparts, there is conflicting data regarding their relative prognosis. To better characterize outcome and identify patient and treatment factors which affect survival, the authors analyzed cases of adult cerebellar GBM from the Surveillance, Epidemiology, and End Results database. A total of 247 adult patients with cerebellar GBM were identified, accounting for 0.67% of all adult GBM. Patients with cerebellar GBM were significantly younger than those with supratentorial tumors (56.6 versus 61.8years, p <0.0001), but a larger percentage of patients with supratentorial GBM were Caucasian (91.7% versus 85.0%, p <0.0001). Overall median survival did not differ between those with cerebellar and supratentorial GBM (7 versus 8months, p =0.24), with similar rates of long-term (greater than 2years) survival (13.4% versus 10.6%, p =0.21). Multivariate analysis revealed age greater than 40years (hazard ratio [HR]: 2.20; 95% confidence interval [CI]: 1.47–3.28; p =0.0001) to be associated with worse patient survival, while the use of radiotherapy (HR: 0.33; 95% CI: 0.24–0.47; p <0.0001) and surgical resection (HR: 0.66; 95% CI: 0.45–0.96; p =0.028) were seen to be independent favorable prognostic factors. In conclusion, patients with cerebellar GBM have an overall poor prognosis, with radiotherapy and surgical resection significantly improving survival. As with supratentorial GBM, older age is a poor prognostic factor. The lack of differences between supratentorial and cerebellar GBM with respect to overall survival and prognostic factors suggests these tumors to be biologically similar. [Copyright &y& Elsevier]

Abstract: Purpose: Phenytoin is known to be able to induce cerebellar atrophy in patients with epilepsy. It is also known that a CYP2C9 mutation (*2 or *3) reduces phenytoin metabolism by 25–50% and can increase the risk of phenytoin-related side effects. We examined the influence of CYP2C9 polymorphisms on total cerebellar volume and cerebellar gray and white matter volumes in patients with epilepsy taking phenytoin. Methods: For the genotyping, 100 adult patients with documented epilepsy who had been taking phenytoin for >1 year were selected. From this group, we randomly selected 19 mutant individuals (MT group; CYP2C9*2 and *3) for a whole-brain volume measurement using MRI and 19 wild-type individuals (group WT; CYP2C9*1) with similar clinical and demographic characteristics to those in the MT group for comparison. Total intracranial volume measurements were used to normalize the acquired volumes, which were separated into gray matter volume, white matter volume, and total volume. Results: The MT group exhibited a significant reduction in cerebellar white matter volume (p =0.002) but not in total cerebellar volume. Conclusion: Our study is the first to report evidence linking CYP2C9 polymorphism and a reduction in cerebellar volume in epileptic users of phenytoin. [Copyright &y& Elsevier]

Nicotine is a psychoactive component of tobacco that plays critical roles in the regulation of neuronal circuit function and neuroplasticity and contributes to the improvement of working memory performance and motor learning function via nicotinic acetylcholine receptors (nAChRs). Under in vivo conditions, nicotine enhances facial stimulation-evoked mossy fiber-granule cell (MF-GrC) synaptic transmission, which suggests that nicotine regulates MF-GrC synaptic plasticity in the mouse cerebellar cortex. In this study, we investigated the effects of nicotine on facial stimulation-induced long-term potentiation (LTP) of MF-GrC synaptic transmission in urethane-anesthetized mice. Our results showed that facial stimulation at 20 Hz induced an MF-GrC LTP in the mouse cerebellar granular layer that was significantly enhanced by the application of nicotine (1 μM). Blockade of α4β2 nAChRs, but not α7 nAChRs, during delivery of 20 Hz facial stimulation prevented the nicotine-induced facilitation of MF-GrC LTP. Notably, the facial stimulation-induced MF-GrC LTP was abolished by an N-methyl-D-aspartate (NMDA) receptor antagonist, but it was restored by additional application of nicotine during delivery of 20 Hz facial stimulation. Furthermore, antagonism of α4β2 nAChRs, but not α7 nAChRs, during delivery of 20 Hz facial stimulation prevented nicotine-induced MF-GrC LTP. Moreover, inhibition of nitric oxide synthase (NOS) abolished the facial stimulation-induced MF-GrC LTP, as well as the effect of nicotine on it. Our results indicated that 20 Hz facial stimulation induced MF-GrC LTP via an NMDA receptor/nitric oxide (NO) cascade, but MF-GrC LTP was enhanced by nicotine through the α4β2 AChR/NO signaling pathway. These results suggest that nicotine-induced facilitation of MF-GrC LTP may play a critical role in the improvement of working memory performance and motor learning function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cao, Bing, Xu, Zhang, Chu, Hong and Qiu.)

Childhood ataxia is characterized by impaired balance and coordination primarily because of cerebellar dysfunction. Friedreich ataxia, a form of childhood ataxia, is the most common multisystem autosomal recessive disease. Most of these patients are homozygous for the GAA repeat expansion located on the first intron of the frataxin gene on chromosome 9. Mutations in the frataxin gene impair mitochondrial function, increase reactive oxygen species, and trigger redistribution of iron in the mitochondria and cytosol. Targeted therapies for Friedreich ataxia are undergoing testing. In addition, a centralized database, patient registry, and natural history study have been launched to support clinical trials in Friedreich ataxia. The 2011 Neurobiology of Disease in Children symposium, held in conjunction with the 40th annual Child Neurology Society meeting, aimed to (1) describe clinical features surrounding Friedreich ataxia, including cardiomyopathy and genetics; (2) discuss recent advances in the understanding of the pathogenesis of Friedreich ataxia and developments of clinical trials; (3) review new investigations of characteristic symptoms; and (4) establish clinical and biochemical overlaps in neurodegenerative diseases and possible directions for future basic, translational, and clinical studies. [ABSTRACT FROM AUTHOR]

Familial hemiplegic migraine (FHM) type 1 is a rare monogenic dominant autosomal disease due to CACNA1A gene mutations. Besides the classical phenotype, mutations on CACNA1A gene are associated with a broader spectrum of clinical features including cerebellar ataxia, making FHM1 a complex channelopathy. We report the case of a patient carrying the p.Arg583Gln mutation affected by hemiplegic migraine and late onset ataxia and we performed a literature review about the clinical features of p.Arg583Gln. Although p.Arg583Gln mutations are associated with a heterogeneous phenotype, carriers present cerebellar signs which consisted generally in ataxia and dysmetria, with intention tremor appearing mostly in advanced age, often progressive and permanent. The heterogeneous spectrum of CACNA1A gene mutations probably causes sporadic hemiplegic migraine (SHM) to be misdiagnosed. Given the therapeutic opportunities, SHM/FHM1 should be considered in differential diagnosis of patients with cerebellar ataxia and migraine with aura. [ABSTRACT FROM AUTHOR]

Linear and angular control of trunk and leg motion during curvilinear navigation was investigated in subjects with cerebellar ataxia and age-matched control subjects. Subjects walked with eyes open around a 1.2-m circle. The relationship of linear to angular motion was quantified by determining the ratios of trunk linear velocity to trunk angular velocity and foot linear position to foot angular position. Errors in walking radius (the ratio of linear to angular motion) also were quantified continuously during the circular walk. Relative variability of linear and angular measures was compared using coefficients of variation (CoV). Patterns of variability were compared using power spectral analysis for the trunk and auto-covariance analysis for the feet. Errors in radius were significantly increased in patients with cerebellar damage as compared to controls. Cerebellar subjects had significantly larger CoV of feet and trunk in angular, but not linear, motion. Control subjects also showed larger CoV in angular compared to linear motion of the feet and trunk. Angular and linear components of stepping differed in that angular, but not linear, foot placement had a negative correlation from one stride to the next. Thus, walking in a circle was associated with more, and a different type of, variability in angular compared to linear motion. Results are consistent with increased difficulty of, and role of the cerebellum in, control of angular trunk and foot motion for curvilinear locomotion. [ABSTRACT FROM AUTHOR]

INTRODUCTION Use of imaging to predict pre-operative likelihood of histopathology in pediatric tumors involving the cerebellum and/or fourth ventricle is potentially beneficial to the neurosurgical and neuro-oncological teams. The objective of the current report was to assess the correlation between radiologic evidence of tumor exit from the outlet foramina of the fourth ventricle with final histopathologic diagnosis. METHODS In 50 consecutive pediatric patients who underwent craniotomy for primary resection of a cerebellar neoplasm, pre-operative MRI was reviewed for evidence of tumor exit from the outlet foramina of fourth ventricle. RESULTS Evidence of tumor exit from the outlet foramina of fourth ventricle on MRI was found to be especially predictive of ependymoma. Specifically, this radiologic finding was 90% specific (37/41) and 100% sensitive (9/9) for histopathologic diagnosis of ependymoma. Of note, 2 of 18 medulloblastomas and 2 of 2 grade IV gliomas also demonstrated evidence of tumor exit. CONCLUSION Evidence of tumor exit from the outlet foramina of fourth ventricle on pre-operative MRI predicts histopathologic diagnosis of ependymoma with high accuracy. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to determine the correlation between fetal transverse cerebellar diameter (TCD) and gestational age of male and female fetus in women under low-risk prenatal care between the 13th and 40th week of gestation. Methods: A cross-sectional study was carried out with 184 pregnant women, at the age of 18 years or more, gestational age ranging from 13 to 40 weeks, with a single fetus. A single TCD measurement by ultrasound was used for each fetus. Correlations between fetal TCD and gestational age were determined for the whole sample and each gender separately. Results: We identified 102 males and 82 female fetuses. A linear correlation was observed between fetal TCD and gestational age for the whole sample (r = 96.9%; p < 0.001). A significant linear correlation was also observed for both males (r = 97.0%; p < 0.001) and females (r = 96.9%; p < 0.001). Comparing the regression lines between genders, no significant difference was observed. Conclusions: The data of this study suggest TCD fetal ultrasound as a predictive biometric parameter of gestational age independently of fetal gender in the last two trimesters of a pregnancy. [ABSTRACT FROM AUTHOR]

Abstract: Tremor is a frequent disabling consequence of many neurological conditions. We performed a search of MEDLINE, CINAHL, EMBASE and the Cochrane Library to identify all primary research studies published up to November 2010 which investigated non-pharmacological and non-surgical treatments for tremor in humans. Neuromuscular physiotherapy, strength training and functional electrical stimulation show promise in their applicability and adaptability. Limb cooling may not be feasible for continuous management, but may be appropriate for specific tasks. Tremor-suppressing orthoses based on viscous materials, weighted splints and vibration therapies need further evaluation especially in the domiciliary setting and applied to improving personal activities of daily living. The evidence base for many rehabilitation interventions in tremor is poor. Future research should focus on high quality randomized controlled trials of non-pharmacological and non-surgical interventions which show promise. [Copyright &y& Elsevier]

Mouchet-Mages S, Rodrigo S, Cachia A, Mouaffak F, Olie JP, Meder JF, Oppenheim C, Krebs MO. Correlations of cerebello-thalamo-prefrontal structure and neurological soft signs in patients with first-episode psychosis. This study aimed at determining brain structural imaging correlates of neurological soft signs (NSS) in patients suffering from a first-episode psychosis. Fifty-two patients with a DSMIV diagnosis of first-episode psychosis (schizophrenia or schizophrenia spectrum disorder) were consecutively included. Subjects were assessed using a standardized neurological examination for motor coordination, motor integration and sensory integration. Anatomical magnetic resonance images (MRI) were analysed in the whole brain using optimized voxel-based morphometry. Neurological soft signs (NSS) total score ( P-corrected = 0.013) and motor integration subscore ( P-corrected = 0.035) were found to negatively correlate with grey matter structure of the dorsolateral prefrontal cortices. Motor coordination subscore was positively correlated with grey matter structure of the thalami ( P-corrected = 0.002) and negatively with white matter structure of the cerebellum ( P-corrected = 0.034). The addition of age and gender as covariate yielded similar results. We did not find any correlation between neither sensory integration subscore and grey matter structure nor NSS total score, motor integration subscore and voxel-based morphometry (VBM) white matter structure. Structural alteration in the cerebello-thalamo-prefrontal network is associated with neurological soft signs in schizophrenia, a candidate network for 'cognitive dysmetria'. [ABSTRACT FROM AUTHOR]

Liponeurocytoma is not exclusive to the cerebellar or fourth ventricular location. Since its inclusion in the central nervous system tumor classification in 2000, six cases with similar radiological, histomorphological and immunohistochemical features have also been described in the lateral ventricles. In the present study, we report clinical, radiological and pathological findings of three supratentorial and one cerebellar liponeurocytoma from our records, evaluated with an extensive panel of immunohistochemistry, and review published cases in the literature. The immunohistochemical pattern of supratentorial and infratentorial liponeurocytomas are almost identical, which indicates that these tumors are homologous. [ABSTRACT FROM AUTHOR]

We describe three children with genetically different sodium channel alpha 1 subunit ( SCN1A) mutation associated epilepsy who experienced a sudden and sustained neurologic regression following status epilepticus in two and acute sepsis in one. Neuroimaging showed evidence of cerebral ischemia in one, but the other two cases showed cerebellar signal abnormalities. The selectivity of cerebellar white matter change suggests a different mechanism of injury or increased susceptibility of this brain region to injury in at least some patients with SCN1A mutations. This report adds to the spectrum and mechanism of acute neurologic deterioration and functional deficit associated with SCN1A mutations, which remains to be fully understood. [ABSTRACT FROM AUTHOR]

Joubert syndrome is an autosomal recessive disorder characterized by partial or complete agenesis of the cerebellar vermis. Clinical features include attacks of tachypnea alternating with respiratory pauses, abnormal ocular movements, severe psychomotor retardation and ataxia. A 12 year- old male patient was diagnosed as Joubert syndrome by clinical and radiological findings. After 10 years follow up, his ataxic symptoms improved to be enough to supply self care. Our case was interesting because of his good prognosis which is rare for this condition. [ABSTRACT FROM AUTHOR]

In earlier work the concept of Orientation (O) was proposed as the key factor in successful literacy acquisition. This article develops that idea further to discuss the potential of Orientation Theory (OT) to unite current conflicts between apparently opposing theories of dyslexia. After briefly outlining these theoretical differences it is proposed that by adopting an ecological paradigm, in place of a “within child” model, the three major theories of dyslexia can be seen to offer valid but partial explanations within the wider concept of orientation. Orientation (O) and Genetic Identity (GI) generated as the two essential factors of OT are described in relation to these three theories. The application of OT in both UK educational policy and early years development are outlined. Finally, some answers to Nicolson's six questions for dyslexia are provided. [ABSTRACT FROM AUTHOR]

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Hemangioblastomas (HBMs) are highly vascular tumors of the central nervous system. Sporadic HBMs are nearly always solitary, and solitary HBMs are similar to intracranial arteriovenous malformations due to their highly vascular characteristics. However, to the best of our knowledge, cases of HBM in the cerebellum mimicking an aneurysm have never been reported in the literature. The present study reports a case of an HBM on the right cerebellar hemisphere mimicking an aneurysm, which originated from the right posterior inferior cerebellar artery, as determined using magnetic resonance angiography and digital subtraction angiography. The patient was admitted the Department of Neurosurgery at the Tsinghua University Yuquan Hospital (Beijing, China) in January 2015 due to a 4-year history of intermittent headaches. The diagnosis of an HBM was determined during surgery and the tumor was totally resected by changing the operation technique, with no complications. In conclusion, it is difficult to distinguish between HBMs and intracranial vascular diseases, particularly aneurysms. Surgeons should consider the possibility carefully prior to surgery and careful prepare for each eventuality. [ABSTRACT FROM AUTHOR]

Primary cerebellar agenesis is a rare entity. To the best of our knowledge, eleven living cases have been reported till date. Most of these were associated with some degree of motor impairment. We present a case of cerebellar agenesis in a child who presented with cognitive abnormalities leading to poor performance at school. No motor impairment was seen. Among the eleven cases reported earlier, only one case showed lack of motor impairment. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To investigate the efficacy of magnetic stimulation over the posterior fossa (PF) as a non-invasive assessment of cerebellar function in man. Methods: We replicated a previously reported conditioning-test paradigm in 11 healthy subjects. Transcranial magnetic stimulation (TMS) at varying intensities was applied to the PF and motor cortex with a 3, 5 or 7ms interstimulus interval (ISI), chosen randomly for each trial. Surface electromyogram (EMG) activity was recorded from two intrinsic hand muscles and two forearm muscles. Responses were averaged and rectified, and MEP amplitudes were compared to assess whether suppression of the motor output occurred as a result of the PF conditioning pulse. Results: Cortical MEPs were suppressed following conditioning-test ISIs of 5 or 7ms. No suppression occurred with an ISI of 3ms. PF stimuli alone also produced EMG responses, suggesting direct activation of the corticospinal tract (CST). Conclusions: CST collaterals are known to contact cortical inhibitory interneurones; antidromic CST activation could therefore contribute to the observed suppression of cortical MEPs. Significance: PF stimulation probably activates multiple pathways; even at low intensities it should not be regarded as a selective assessment of cerebellar function unless stringent controls can confirm the absence of confounding activity in other pathways. [Copyright &y& Elsevier]

Abstract: Cerebellar dysfunction is associated with deficits in the control of movement extent, as well as changes in the amplitude and relative amounts of acceleration and deceleration and action tremor. The present study sought to identify whether cerebellar symptoms occur in the handwriting of intoxicated individuals. Twenty participants in two sub-groups (alcohol dependent and non-alcohol dependent) were asked to write four cursive letter ‘l’s on a Wacom SD420 graphics tablet before and after consumption of a dose of vodka and orange producing a peak blood alcohol concentration of 0.048%. There was a relationship between blood alcohol concentration and stroke length. Kinematic analysis of handwriting indicated increases in the relative proportions of time spent in acceleration and increases in spectral power around 4Hz. It was found that alcohol intoxication causes symptoms of cerebellar dysfunction, and that alcohol dependent individuals had less ballistic handwriting compared to non-alcohol dependent participants. [Copyright &y& Elsevier]

Abstract: We encountered a case of head trauma with very unusual delayed events. A 68-year-old woman was admitted to our hospital after receiving a direct impact to her occiput in a traffic accident. Head CT scans showed a thin acute epidural hematoma in the posterior fossa corresponding to a linear fracture, followed by late onset of contrecoup left frontal epidural hematoma and subsequent cerebellar contusion in the right cerebellar hemisphere. Fifteen days after the trauma, the patient developed mild motor weakness of right upper extremity. MRIs demonstrated an infarct in the territory of the left recurrent artery of Heubner. Although rare, atypical late events in patients with head trauma as reported here should be taken into consideration during subacute follow-up periods. [Copyright &y& Elsevier]

Extragonadal teratomas in adulthood are exceptionally rare and usually not located within the cerebellum. We here report on a 66-year-old male patient clinically presenting with chronic occipital headache and episodes of severe vertigo. Neuroradiological investigations revealed a hemorrhagic tumor mass in the cerebellar vermis which was surgically removed and histologically diagnosed as mature teratoma. Hence, the presented case is extraordinary with regard to age, late clinical onset of symptoms and cerebellar location. Late clinical manifestation of the tumor in this case is probably due to an acute late-onset hemorrhage within the tumor. [ABSTRACT FROM AUTHOR]

Lurcher mutant mice represent a model of olivocerebellar degeneration. They are used to investigate cerebellar functions, consequences of cerebellar degeneration and methods of therapy influencing them. The aim of the work was to assess the effect of foetal cerebellar graft transplantation, repeated enforced physical activity and the combination of both these types of treatment on motor skills, spontaneous motor activity and spatial learning ability in adult B6CBA Lurcher mice. Foetal cerebellar grafts were applied into the cerebellum of Lurchers in the form of solid tissue pieces. Enforced motor activity was realised through rotarod training. Motor functions were examined using bar, ladder and rotarod tests. Spatial learning was tested in the Morris water maze. Spontaneous motor activity in the open field was observed. The presence of the graft was examined histologically. Enforced physical activity led to moderate improvement of some motor skills and to a significant amelioration of spatial learning ability in Lurchers. The transplantation of cerebellar tissue did not influence motor functions significantly but led to an improvement of spatial learning ability. Mutual advancement of the effects of both types of treatment was not observed. Spontaneous motor activity was influenced neither by physical activity nor by the transplantation. Physical activity did not influence the graft survival and development. Because nerve sprouting and cell migration from the graft to the host cerebellum was poor, the functional effects of the graft should be explained with regard to its trophic influence rather than with any involvement of the grafted cells into neural circuitries. [ABSTRACT FROM AUTHOR]

• Tremor severity is associated with reduced tremor-related quality of life in people with MS • Quantifying tremor related quality of life in people with MS is possible with QUEST • Validation of QUEST for use in quantifying tremor related quality of in MS • Health related Quality of life scales underperform against QUEST when measuring tremor related quality of life in people with MS Upper limb tremor is common in people with multiple sclerosis (pwMS) and can affect day to day function, impacting on their tremor related quality of life (tremor-QOL). The Quality of Life in Essential Tremor Questionnaire (QUEST) is a tremor-QOL scale, however it has not been validated for use in pwMS. This is in contrast to the Multiple Sclerosis Impact Scale (MSIS-29), a MS health related QOL (MS-QOL) scale validated in pwMS. The aim of this study was to quantify tremor-QOL in pwMS using both the QUEST and MSIS-29 and establish the convergent validity of the QUEST scale with the MSIS-29. Data were derived from an existing registered clinical trial studying the efficacy of Botox (onabotulinumtoxinA) compared to placebo in pwMS-related upper limb tremor (ACTRN12617000379314). We determined MS-related disability (Expanded Disability status scale score (EDSS)), tremor severity (Bain and Findley Clinical Tremor Rating Scale (Bain)), cerebellar function (Scale for the Assessment and rating of Ataxia (SARA)), and upper limb manual dexterity (9 Hole Peg Test (9-HPT)). The QUEST and MSIS-29 were used to quantify tremor-QOL and MS-QOL respectively. Convergent validity was investigated by examining the correlation between QUEST and MSIS-29, and the pattern of correlation of the two scales compared to the EDSS, SARA, BAIN and 9-HPT. Our cohort of 57 patients (16 male; 41 female), mean age of 47.6, had moderate MS-related disability with median EDSS score of 5 (IQR = 3.5). Median Bain score was 8, indicating mild tremor severity, which corresponded to mild to moderately poor tremor-QOL given mean Quest Summary Index (QSI) of 45.7. QSI correlated to tremor severity as measured by Bain total score (rs(55) = 0.339, p < 0.01), manual dexterity as measured by 9-HPT (rs(55) = 0.304, p < 0.05), and MS disease activity measured by EDSS (rs(55) = 0.347, p < 0.01). MSIS-29 also showed correlations to EDSS, and 9-HPT, but did not correlate to Bain total score. There was a strong relationship between QSI and MSIS-29 in pwMS (r(55) = 0.709, p < 0.01). In this cross-sectional study, we found that both the MS-QOL and tremor-QOL of pwMS with upper limb tremor was reduced. We were also the first to demonstrate that tremor-QOL in pwMS with upper limb tremor can be measured using the QUEST, which may be better suited for use in pwMS affected by arm-tremor than the MSIS-29. There is a lack of literature to specifically address tremor-QOL in pwMS, and more research is warranted. [ABSTRACT FROM AUTHOR]

Introduction: With the advent of neuroimaging modalities specifically, magnetic resonance imaging (MRI), recognition of developmental defects of posterior fossa has greatly improved. The Aim: Is to delineate the clinical, cytogenetics and radiological features of patients with mid-hindbrain anomalies. Patient and Methods: Twenty-three patients with mid-hind brain malformations were included in this study. Complete clinical evaluation, cytogenetic analysis and neuroradiological study were done for each patient. Patients' sex ratio was (M: F/ 0.9:1) and the mean age was 2.17 years. Parental consanguinity was 86.9 % and positive family history was recorded in 7 families. Based on clinico-radiological findings, patients were categorized as Joubert syndrome and related cerebellar disorders (34.8%), pontocerebellar hypoplasia (26.1%), lissencephaly cerebellar hypoplasia (13%), isolated cobblestone lissencephaly with normal muscle and eye (8.7%), isolated vermian hypoplasia (13%) and retrocerebellar cyst (4.4%). Results: Cytogenetic analysis revealed abnormalities in 3 patients (13%); pericentric inversion of chromosome 8 in a patient with lissencephaly cerebellar hypoplasia, del 5p14.3-pter delineating Cri du chat syndrome and associated with vermian hypoplasia and del 18q21.1-qter in a patient with retrocerebellar cyst due to paternal balanced translocation t (4;18). FISH for specific locus and whole chromosomal painting were used to document the assigned aberrations. Although most of the cerebellar malformations are of Mendelian inheritance, this study emphasizes the importance of chromosomal analysis for patients with posterior fossa anomalies. With more researches describing clinico-radiological characterization of hind brain dysgenesis will allow better understanding of these disorders, further delineation of relevant syndromes and new genes identification. [ABSTRACT FROM AUTHOR]

Schizophrenia and autism are neurodevelopmental diseases that have genetic as well as environmental etiologies. Both disorders have been associated with prenatal viral infection. Brain imaging and postmortem studies have found alterations in the structure of the cerebellum as well as changes in gene expression. Our laboratory has developed an animal model using prenatal infection of mice with human influenza virus that has demonstrated changes in behavior, pharmacology, structure, and gene expression in the brains of exposed offspring. In the current communication we describe altered expression of cerebellar genes associated with development of brain disorder in a mouse model for schizophrenia and autism and correlate these changes with those involved in the pathology of these two disorders. [ABSTRACT FROM AUTHOR]

Responding to an open request, the principle of recursive genome function (PRGF) is put forward, effectively reversing two axioms of genomics as we used to know it, prior to the Encyclopedia of DNA Elements Project (ENCODE). The PRGF is based on the reversal of the interlocking but demonstrably invalid central dogma and “Junk DNA” conjectures that slowed down the advance of sound theory of genome function, as far as information science is concerned, for half a century. PRGF illustrates the utility of the class of recursive algorithms as the intrinsic mathematics of post-ENCODE genomics. A specific recursive algorithmic approach to PRGF governing the growth of the Purkinje neuron is sketched, building the structure in a hierarchical manner, starting from primary genomic information packets and in each recursion using auxiliary genomic information packets, cancelled upon perusal. The predictive power of the principle and its experimental support are indicated. It is argued that genomics is no longer an exceptional instance of the applicability of recursion throughout the sciences. [ABSTRACT FROM AUTHOR]

Recent discoveries on the way in which the cerebellum carries out higher non-motor functions, have stimulated a proliferation of researches into functional integration and neural mechanisms in the cerebellum. Cerebellar functional asymmetry is a special characteristic of cerebellar functional organization and the cerebro-cerebellar circuitry that underlies task performance. Multi-level neuroimaging studies demonstrate that cerebellar functional asymmetry has a rather complex pattern, and may be correlated with practice or certain disorders. In this review, we summarize some new and important advances in the understanding of functional laterality of the cerebellum in primary motor and higher cognitive functions, and highlight the differences in the patterns of cerebellar functional asymmetry in the various functional domains. We propose that cerebellar functional asymmetry may be associated with the pattern of connectivity between a large number of widely distributed brain areas and between special cerebellar functional regions. It is suggested that cerebro-cerebellar circuits in particular play an important role in cerebellar functional asymmetry. Finally, we propose that multi-scale connectivity analyses and careful studies of high-level cerebellar functional asymmetry would make an important contribution to the understanding of the human cerebellum and cerebral neural networks. [ABSTRACT FROM AUTHOR]

Background: The principal features of the cerebellar infarcts are ataxia, failure of coordination, gait instability, and articulation and eye movement disabilities. Language disabilities are also seen with cerebellar lesions, but there are difficulties in diagnosis. This study was planned to evaluate the effects of cerebellar lesions on language functions and the relation between these functions and lesion type, age, and education level. Methods: A total of 20 patients, 13 male (65%) and 7 female (35%), were included in this study. Twenty control subjects with similar demographic characteristics were also included. The mean age of the patient group was not statistically different. Results: Patients with vermal lesions had significantly higher performance than patients with paravermal lesions when evaluating the understanding of hearing and total aphasia score. Understanding of reading function was significantly better in the patients with small lesions compared with those with large lesions. When the aphasia parameters were compared between the patient and control groups, significant differences were found for all parameters, which reflected the language abilities understanding, naming, true-wrong questions, complex questions, comparing, repeating, and total aphasia score. Reading and writing functions were also significantly different between the patients and the control subjects. Conclusion: We found that the cerebellum contributes in several language parameters. These functions show difference according to localization and lesion volume of cerebellar disease. Aphasia should be explored as an important parameter when evaluating the loss of function in patients with cerebellar lesions. [Copyright &y& Elsevier]

Abstract: Although G protein-coupled MT1 and MT2 melatonin receptors are expressed in neurons of the mammalian brain including in humans, relatively little is known about the influence of native MT1 and MT2 melatonin receptors on neuronal melatonin signaling. Whereas human cerebellar granule cells (CGC) express only MT1 receptors, mouse CGC express both MT1 and MT2. To study the effects of altered neuronal MT1/MT2 receptors, we used CGC cultures prepared from immature cerebella of wild-type mice (MT1/MT2 CGC) and MT1- and MT2-knockout mice (MT2 and MT1 CGC, respectively). Here we report that in MT1/MT2 cultures, physiological (low nanomolar) concentrations of melatonin decrease the activity (phosphorylation) of extracellular-signal-regulated kinase (ERK) whereas a micromolar concentration was ineffective. Both MT1 and MT2 deficiencies transformed the melatonin inhibition of ERK into melatonin-induced ERK activation. In MT1/MT2 CGC, 1 nM melatonin inhibited serine/threonine kinase Akt, whereas in MT1 and MT2 CGC, this concentration was ineffective. Under these conditions, both MT1 and MT2 deficiencies prevented melatonin from inhibiting forskolin-stimulated cAMP levels and cFos immunoreactivity. We demonstrated that selective removal of native neuronal MT1 and MT2 receptors has a profound effect on the intracellular actions of low/physiological concentrations of melatonin. Since the expression of MT1 and MT2 receptors is cell-type-specific and species-dependent, we postulate that the pattern of expression of neuronal melatonin receptor types in different brain areas and cells could determine the capabilities of endogenous melatonin in regulating neuronal functioning. [Copyright &y& Elsevier]

Abstract: We present a 62-year-old man with a high-grade cerebellar ganglioglioma with ataxia. Gangliogliomas are rare tumours which usually occur in the first 3 decades of life. There have only been a small number of grade IV gangliogliomas reported in the literature. [Copyright &y& Elsevier]

Objectives: Autosomal dominant cerebellar ataxias are clinically and genetically heterogeneous neurodegenerative disorders. There is no known treatment to prevent neuronal cell death in these disorders. Current treatment is purely symptomatic; ataxia is one of the most disabling symptoms and represents the main therapeutic challenge. A previous case report suggesting benefit from administration of high dose piracetam inspired the present study of the efficacy of this agent in patients with cerebellar ataxia. Piracetam is a low molecular weight derivative of γ-aminobutyric acid. Although little is known of its mode of action, its efficacy has been documented in a wide range of clinical indications, such as cognitive disorders, dementia, vertigo and dyslexia, as well as cortical myoclonus. The present report investigated the role of high dose piracetam in patients with cerebellar ataxia. Methods: Eight patients with autosomal dominant cerebellar ataxia were given intravenous piracetam 60 g/day by a structured protocol for 14 days. The baseline and end-of-the study evaluations were based on the International Cooperative Ataxia Rating Scale. Results: Statistical analysis demonstrated a significant improvement in the patients’ total score ( P = 0·018) and a subscale analysis showed statistical significance for only the posture and gait disturbances item ( P = 0·018). Conclusion: This study is providing good clinical observation in favour of high dose piracetam infusion to reduce the disability of the patients by improving their gait ataxia. [ABSTRACT FROM AUTHOR]

We present a series of cases of phenytoin toxicity where the diagnosis was initially missed. These patients all suffered unnecessary morbidity or investigations. The side-effects and unusual pharmacokinetics of phenytoin are discussed, as well as the array of potential drug interactions. We remind clinicians that phenytoin toxicity can easily mimic a cerebellar lesion or alcohol intoxication, and suggest that in accordance with National Institute for Clinical Excellence (NICE) guidelines phenytoin should no longer be used as a first-line treatment for epilepsy. [ABSTRACT FROM AUTHOR]

Abstract: The development of microarrays for the screening of gene expression has highlighted the importance of obtaining high quality RNA. We have investigated whether it was possible to obtain RNA of sufficiently good quality from postmortem human tissue using samples obtained from the New Zealand Neurological Foundation Human Brain Bank. We have investigated the effect of PM delay, the duration of the agonal state, the tissue pH, the age at death and the sex of the patient on the quality of normal human brain tissue and tissue from patients with various neurodegenerative conditions. Postmortem delay was shown to affect the RNA quality adversely, but the magnitude of the effect was small. While cerebellar RNA quality was not always an exact predictor of the RNA quality in other brain regions of interest, it was shown to have some predictive value and can be used as a preliminary indicator. The principle finding was that RNA quality is most strongly affected by the pH of the tissue, with both the pH and the RNA quality being influenced by the mode of death. [Copyright &y& Elsevier]

Introduction: Loss of vestibular information from one labyrinth produces marked asymmetries of postural and ocular motor control, which resolve over time. Recent developments in mouse genetic engineering, which allow the generation of transgenic and knockout mutant mice, provide a unique opportunity to bridge the gap between the molecular mechanisms that underlie compensation and behaviour. Method: We compared compensation following unilateral labyrinthectomy in wild-type mice and a cerebellar-dysfunctional mouse (the Lurcher mutant). The Lurcher mutant is characterized by a point mutation in the ionotropic glutamate receptor delta2 subunit gene that results in loss of all Purkinje cells. To further investigate this question, we characterized vestibular compensation in a strain of mutant mice that completely lack cerebellar Purkinje cells. Results: Static signs resolved within 24 hours in wild-type mice but did not fully resolve in Lurcher mice. Dynamic signs were evaluated by the quantitative analysis of vestibulo-ocular (VOR) and vestibulocollic (VCR) reflexes. The VOR assessed at 0.5 Hz exhibited increasing gain from day 1 to day 5, reaching control levels by day 20 for the wild-type mice. In contrast, Lurcher mutant mice showed significantly less compensation over this same period. VOR compensation in the mutant mice was slightly more robust in response to high acceleration thrusts but again never reached control levels. Similarly, VCR gains showed limited compensation and remained subnormal in mutant mice. Conclusion: Compensation for dynamic signs starts at day 5 after unilateral labyrinthectomy in normal mice. Cerebellar dysfunctional mutant mice do not compensate for static signs and show limited vestibular compensation for dynamic signs only. We conclude that other noncerebellar pathways for vestibular compensation exist, and our findings emphasize the need for these to be further explored. [ABSTRACT FROM AUTHOR]

Previously, we performed an MRI study that revealed smaller volumes of the subregions of the cerebellar vermis in men and women with chronic schizophrenia. An issue that arose from that study was whether similar structural changes in the cerebellum are found in patients with first-episode schizophrenia. In the present study, MRI scans were acquired from 14 drug-naive patients with first-episode schizophrenia and 16 healthy subjects, and used to measure the volumes of their cerebellar subregions. Positive symptom, negative symptom and cognitive cluster scores were attained using the Positive and Negative Syndrome Scale. Patients with first-episode schizophrenia had reduced volumes of the anterior vermis and posterior superior vermis compared with healthy subjects. We confirmed that there was a volume reduction of the cerebellar vermis in drug-naive patients with first-episode schizophrenia. Smaller volumes of the posterior superior vermis were associated with worse cognitive cluster scores in patients with first-episode schizophrenia. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The cerebellum has long been considered to be mainly involved in motor function. In the last 20 years, evidence from neuroimaging studies and from investigations of patients with cerebellar lesions has shown that the cerebellum plays a role in a range of cognitive functions. While cerebellar contributions have been shown for learning and memory, the cerebellum has also been linked to higher order cognitive control processes frequently referred to as executive functions. Although it is widely accepted that the cerebellum contributes to cognitive processing, the nature of cerebellar involvement is not well understood. The present paper focuses on the role of the cerebellum in executive processing, reviewing findings derived from neuroimaging studies or from studies investigating deficits related to cerebellar dysfunction. As executive functions cannot be considered as a unitary concept, special emphasis is put on cerebellar contributions to different aspects of executive control such as working memory, multitasking or inhibition. Referring to models derived from motor control, possible mechanisms of cerebellar involvement in executive processing are discussed. Finally, methodological problems in assessing executive deficits in general and in assessing the cerebellar contribution to executive processing in particular are addressed. [ABSTRACT FROM AUTHOR]

Abstract: We report a 45-year-old, non-alcoholic woman with ovarian cancer who presented with acute impairment of consciousness. Cranial MRI revealed symmetrical and bilateral increased signal intensities of the corpus callosum and the dentate nucleus, without contrast enhancement. The findings are comparable with Marchiafava-Bignami disease (MBD), although pathological confirmation was not possible. Most of the reported cases of MBD are related to chronic ingestion of red wine and/or related with a nutritional cause. We suggest that this patient may suffer a MBD possible related to the ovarian cancer. [Copyright &y& Elsevier]

Surgical excision of cerebellar haemangioblastomas, once they become Symptomatic, is the standard treatment in patients with von Hippel-Lindau disease. This case report describes a von Hippel-Lindau disease patient with a rare recurrent symptomatic dural based cystic haemangioblastoma. [ABSTRACT FROM AUTHOR]

Abstract: Certain discrete areas of the CNS exhibit enhanced sensitivity towards MeHg. To determine whether GSH is responsible for this particular sensitivity, we investigated its role in MeHg-induced oxidative insult in primary neuronal and astroglial cell cultures of both cerebellar and cortical origins. For this purpose, ROS and GSH were measured with the fluorescent indicators, CMH2DCFDA and MCB. Cell associated-MeHg was measured with 14C-radiolabeled MeHg. The intracellular GSH content was modified by pretreatment with NAC or DEM. For each of the dependent variables (ROS, GSH, and MTT), there was an overall significant effect of cellular origin, MeHg and pretreatment in all the cell cultures. A trend towards significant interaction between origin×MeHg×pretreatment was observed only for the dependent variable, ROS (astrocytes p =0.056; neurons p =0.000). For GSH, a significant interaction between origin×MeHg was observed only in astrocytes (p =0.030). The cerebellar cell cultures were more vulnerable (astrocytesmean =223.77; neuronsmean =138.06) to ROS than the cortical cell cultures (astrocytesmean =125.18; neuronsmean =107.91) for each of the tested treatments. The cell associated-MeHg increased when treated with DEM, and the cerebellar cultures varied significantly from the cortical cultures. Non-significant interactions between origin×MeHg×pretreatment for GSH did not explain the significant interactions responsible for the increased amount of ROS produced in these cultures. In summary, although GSH modulation influences MeHg-induced toxicity, the difference in the content of GSH in cortical and cerebellar cultures fails to account for the increased ROS production in cerebellar cultures. Hence, different approaches for the future studies regarding the mechanisms behind selectivity of MeHg have been discussed. [Copyright &y& Elsevier]

Context There is an emerging body of literature regarding multiple sclerosis (MS) in African-Americans (AA) that suggests more rapid progression and a worse prognosis in this group. A phenotype of opticospinal MS has been proposed by some publications. Objective To determine whether AA with MS have a different clinical phenotype, different distribution of clinical subtypes, and/or different levels of disability than Caucasians (CA) with MS. Specifically, is the disability attributable to severe cerebellar disease, which limits ambulation and function? Design: Retrospective chart analyses of a patient cohort from an academic MS center. Patients A total of 86 AA were identified with MS, 79 were followed for ≥ 5 years. The control group consisted of 80 randomly-selected CA with MS and similar follow-up. Outcome measures EDSS at diagnosis, five-year follow-up, and last follow-up; time to walking assistance device; disease subtype; involved functional systems. Results AA MS patients displayed more cerebellar dysfunction, and worse EDSS scores at diagnosis, at four to six years follow-up from diagnosis, and at last follow-up compared to the CA MS patients with similar length of follow-up. AA MS patients had earlier and more frequent gait difficulty requiring use of a cane or wheelchair. AA MS patients had a higher prevalence of primary progressive (PP) MS (22 versus 9%) and a lower rate of relapsing-remitting (RR) MS (30 versus 52%) compared to CA. Conclusions Compared to CA patients, MS in AA is characterized by a higher incidence of cerebellar dysfunction and a more rapid accumulation of disabilities. In this cohort, AA patients had a relatively higher rate of the PPMS subtype. These data suggest the presence of fundamental differences in the clinical phenotype and the natural history of MS in AA. [ABSTRACT FROM AUTHOR]

Langerhan’s cell histiocytosis (LCH) has been described as a progressive neurological disorder marked by neurological and cognitive decline. The authors here report a case of a childhood LCH sufferer who made a significant recovery of neuropsychological function in the absence of motor recovery in late adolescence. This differential recovery of motor and cognitive functioning may relate to the interaction between LCH and childhood and adolescent neurodevelopmental processes. [ABSTRACT FROM AUTHOR]