Lateral Cerebellar Hemispheres Research Articles

Measurements of the lateral cerebellar hemispheres using near-infrared spectroscopy through comparison between autism spectrum disorder and typical development

The cerebellum plays a vital role in cognition, communication with the cerebral cortex, and fine motor coordination. Near-infrared spectroscopy (NIRS) is a portable, less restrictive, and noninvasive functional brain imaging method that can capture brain activity during movements by measuring the relative oxyhemoglobin (oxy-Hb) concentrations in the blood. However, the feasibility of using NIRS to measure cerebellar activity requires discussion. We compared NIRS responses between areas assumed to be the cerebellum and the occipital lobe during a fine motor task (tying a bow knot) and a visual task. Our results showed that the oxy-Hb concentration increased more in the occipital lobe than in the cerebellum during the visual task (p =.034). In contrast, during the fine motor task, the oxy-Hb concentration decreased in the occipital lobe but increased significantly in the cerebellum, indicating a notable difference (p =.015). These findings suggest that we successfully captured cerebellar activity associated with processing, particularly fine motor coordination. Moreover, the observed responses did not differ between individuals with autism spectrum disorder and those with typical development. Our study demonstrates the meaningful utility of NIRS as a method for measuring cerebellar activity during movements.

Cerebellar axonopathy in Shivers horses identified by spatial transcriptomic and proteomic analyses.

Shivers in horses is characterized by abnormal hindlimb movement when walking backward and is proposed to be caused by a Purkinje cell (PC) axonopathy based on histopathology. Define region-specific differences in gene expression within the lateral cerebellar hemisphere and compare cerebellar protein expression between Shivers horses and controls. Case-control study of 5 Shivers and 4 control geldings ≥16.2 hands in height. Using spatial transcriptomics, gene expression was compared between Shivers and control horses in PC soma and lateral cerebellar hemisphere white matter, consisting primarily of axons. Tandem-mass-tag (TMT-11) proteomic analysis was performed on lateral cerebellar hemisphere homogenates. Differences in gene expression between Shivers and control horses were evident in principal component analysis of axon-containing white matter but not PC soma. In white matter, there were 455/1846 differentially expressed genes (DEG; 350 ↓DEG, 105 ↑DEG) between Shivers and controls, with significant gene set enrichment of the Toll-Like Receptor 4 (TLR4) cascade, highlighting neuroinflammation. There were 50/936 differentially expressed proteins (DEP). The 27 ↓DEP highlighted loss of axonal proteins including intermediate filaments (5), myelin (3), cytoskeleton (2), neurite outgrowth (2), and Na/K ATPase (1). The 23 ↑DEP were involved in the extracellular matrix (7), cytoskeleton (7), redox balance (2), neurite outgrowth (1), signal transduction (1), and others. Our findings support axonal degeneration as a characteristic feature of Shivers. Combined with histopathology, these findings are consistent with the known distinctive response of PC to injury where axonal changes occur without a substantial impact on PC soma.

Field strength difference in extent of artifacts induced by CERTAS Plus valves in patients with idiopathic normal pressure hydrocephalus.

: Post-shunt MRI is usually performed at 1.5T under the general assumption that shunt-related susceptibility artifacts would be greater at higher field strengths. The purpose is to show that imaging post-shunt idiopathic normal pressure hydrocephalus (iNPH) patients at 3T is feasible and with reduced artifacts as compared to 1.5T. We manually measured transverse dimensions of artifact at the levels of lateral ventricles, cerebral aqueduct, and cerebellar hemisphere. Areas/volumes of artifacts were calculated assuming an elliptic/ellipsoid shape. Relative extent of shunt-related artifact between field strengths was rated by 3 readers on a 5-point Likert scale. A Wilcoxon Signed Rank Test was used to compare artifact at 1.5T vs 3T for each sequence, with a significance level set at p < 0.05. Artifact areas were calculated in 22 iNPH patients; artifacts were on average smaller at 3T vs 1.5T on MPRAGE, DWI, and GRE sequences. On T2 FLAIR and T2 FSE, artifacts at 3T were larger than 1.5T. On the qualitative analysis, artifact effects were less at 3T vs 1.5T on DWI, greater at 3T on T2 FSE, and had mixed results on GRE. Our results indicate feasibility of post-shunt imaging with the CERTAS Plus valve at 3T based on shunt-related artifact that is less than or equal in extent to that on 1.5T on most standard clinical imaging sequences. Our findings, corroborated by the qualitative image review, suggest that dedicated clinical imaging sequences for devices may allow for reduction in artifact extent at both 1.5T and 3T.

Occipital and Cerebellar Theta Burst Stimulation for Mal De Debarquement Syndrome.

Individuals with Mal de Debarquement syndrome (MdDS) experience persistent oscillating vertigo lasting for months or years. Transcranial magnetic stimulation (TMS) can modulate the motion perception of MdDS. Twenty-six TMS naive individuals received single administrations of continuous theta burst stimulation (cTBS) over the occipital cortex, cerebellar vermis, and lateral cerebellar hemisphere, in randomized order. A 0-100 point Visual Analogue Scale was used to assess acute changes in oscillating vertigo severity after each session. Repeated treatments were given over the target that led to the most acute reduction in symptoms. All treatments were performed with neuronavigation using the participant's own brain MRI. The Dizziness Handicap Inventory (DHI), MdDS Balance Rating Scale (MBRS), and Hospital Anxiety and Depression Scale (HADS) were assessed weekly at four pretreatment and six posttreatment time points. Twenty participants chose either the occipital cortex (11) or cerebellar vermis (9) targets as most effective in reducing the oscillating vertigo; one chose lateral cerebellar hemisphere; five chose none. After 10 to 12 sessions of 1,200 pulses over the target of choice, 19 of 25 treatment completers noted ≥ 25% reduction, 12 of 25 ≥50% reduction, and 8 of 25 ≥75% reduction in oscillating vertigo intensity. A one-way repeated measures ANOVA of DHI, MBRS, and HADS scores before and after treatment showed significant reductions in DHI, MBRS, and the HADS Anxiety subscore immediately after treatment with most improvement lasting through posttreatment week 6. There were no significant Depression subscore changes. Participants who had chosen vermis stimulation had comparatively worse balance at baseline than those who had chosen occipital cortex stimulation. cTBS over either the occipital cortex or cerebellar vermis is effective in reducing the oscillating vertigo of MdDS acutely and may confer long-term benefits. Sustained improvement requires more frequent treatments.

Language Cerebro-cerebellar Reorganization in Children After Surgery of Right Cerebellar Astrocytoma: a fMRI Study.

Language processing depends on an integrated circuit involving the left supratentorial language areas and the right posterior lateral cerebellar hemisphere (lobule VI, lobule VII, Crus I, and Crus II). Reorganization of the language system after lesions of the cerebral language areas includes also cerebellar relocation. This is the first study assessing functional language reorganization after lesions concerning primarily the cerebellum, using a fMRI paradigm of phonological covert word production task in six children operated for right cerebellar astrocytoma and in 15 typicallydeveloping children. We found right cerebellar and left frontal activations in healthycontrolsand high variability of reorganizational patterns in patients with early right cerebellar lesion. Also lesions not located in the areas typically involved in language tasks (Crus I and Crus II) can cause reorganization between the two hemispheres or hemispheric language reinforcement of the original lateralization. We discuss the role of several variables in determining the reorganizational pattern such as the site, extension, and timing of surgery. No variables revealed as predictors, suggesting that co-occurring influence of other biological and/or pathological factors are not yet demonstrated. Lesions in the postero-lateral cerebellum seem related to less efficient language performances, as an indicator of the system's functioning.

A cerebellar substrate for cognition evolved multiple times independently in mammals.

Given that complex behavior evolved multiple times independently in different lineages, a crucial question is whether these independent evolutionary events coincided with modifications to common neural systems. To test this question in mammals, we investigate the lateral cerebellum, a neurobiological system that is novel to mammals, and is associated with higher cognitive functions. We map the evolutionary diversification of the mammalian cerebellum and find that relative volumetric changes of the lateral cerebellar hemispheres (independent of cerebellar size) are correlated with measures of domain-general cognition in primates, and are characterized by a combination of parallel and convergent shifts towards similar levels of expansion in distantly related mammalian lineages. Results suggest that multiple independent evolutionary occurrences of increased behavioral complexity in mammals may at least partly be explained by selection on a common neural system, the cerebellum, which may have been subject to multiple independent neurodevelopmental remodeling events during mammalian evolution.

Cdc42 Regulates Neuronal Polarity during Cerebellar Axon Formation and Glial-Guided Migration

SummaryCNS cortical histogenesis depends on polarity signaling pathways that regulate cell adhesion and motility. Here we report that conditional deletion of the Rho GTPase Cdc42 in cerebellar granule cell precursors (GCPs) results in abnormalities in cerebellar foliation revealed by iDISCO clearing methodology, a loss of columnar organization of proliferating GCPs in the external germinal layer (EGL), disordered parallel fiber organization in the molecular layer (ML), and a failure to extend a leading process and form a neuron-glial junction during migration along Bergmann glia (BG). Notably, GCPs lacking Cdc42 had a multi-polar morphology and slowed migration rate. In addition, secondary defects occurred in BG development and organization, especially in the lateral cerebellar hemispheres. By phosphoproteomic analysis, affected Cdc42 targets included regulators of the cytoskeleton, cell adhesion and polarity. Thus, Cdc42 signaling pathways are critical regulators of GCP polarity and the formation of neuron-glial junctions during cerebellar development.

One burr-hole craniotomy: Upper retrosigmoid approach in helsinki neurosurgery.

Background:In this video-abstract, we present a one burr-hole craniotomy for the upper retrosigmoid approach developed in Helsinki Neurosurgery to access the lateral cerebellar hemisphere, the cerebellopontine angle, and lateral skull base (e.g. including the posterior petrous bone). This approach may be utilized to manage tumors of the lateral posterior fossa and to perform microvascular cranial nerve decompression of the V or VII cranial nerves. The upper portion of the vertebral-posterior cerebral artery complex, and the anterior inferior cerebellar artery may also be accessed with this technique. Even though the specific location and size of the lesion may vary, this approach accesses all mentioned structures with a very minimal variation.Case Description:The patient with an unsuspected right cerebellopontine angle metastasis from a lung cancer is placed in the park bench position. Spinal drainage is inserted to release 50–100 ml of cerebrospinal fluid. The head and upper torso are elevated so that the head is about 20 cm above the heart level. A single-layer skin incision is made about one inch behind the mastoid process; the exact cranial to caudal location of the incision varies depending on how high or low one has to be from the foramen magnum and locus of pathology. The junction of the sigmoid and the transverse sinus is usually located just caudal to the zygomatic line, between the zygoma and the external occipital protuberance, and posterior to the mastoid line that is running caudally through the tip of the mastoid process. Dissection with curved retractors creates a clean space for the craniotomy. First, a burr-hole is made at the posterior border of the bone flap. Two curved cuts are made towards the mastoid process, allowing the sigmoid sinus to be partially exposed. The bone is cracked after thinning the anterior border of the craniotomy. A few drill holes are then made for tacking-up sutures. Finally, a sinus-based dura opening is performed under the microscope.Conclusion:Here, we described a one burr-hole craniotomy that provides an excellent approach to retrosigmoid lesions.Videolink:http://surgicalneurologyint.com/videogallery/retrosigmoid-approach

Age-related T2 relaxation times at 3 Tesla as a biomarker of infratentorial brain maturation.

The purpose of this study was to examine age-related, infratentorial changes in T2 relaxation times during infancy and childhood using routine MRI data at 3 Tesla. One hundred patients (0-199months) without signal abnormalities on conventional MRI were retrospectively selected from our pool of pediatric MRI examinations. T2 maps based on our routinely acquired triple-echo turbo spin-echo (TSE) sequence were created. Based on their clinical symptoms, the children were divided into 43 controls and 57 diseased children with different clinical diseases. T2 relaxation times were measured in 15 infratentorial brain regions (medullary pyramid, ventral and dorsal pons, middle cerebellar peduncle, dentate nucleus, medial and lateral cerebellar hemisphere each on both sides, and in the cerebellar vermis) investigating age-related changes. Secondly, this study examined whether those changes in T2 values differed between healthy and diseased children. Age significantly reduced T2 relaxation time in all infratentorial brain regions (p<0.05). With increasing age, the T2 relaxation times decreased continuously, faster in the first 9months and slower thereafter. Overall, controls did not differ significantly from diseased children (p>0.05) apart from the dentate nucleus and cerebellar hemispheres in terms of rapid decline (larger in controls) and the right dorsal pons and left pyramid in terms of slow decline (larger in diseased children). In both groups, the later slow decline was almost negligible. Using T2 maps, it was possible to determine age-related T2 relaxation times in the different infratentorial brain regions in this preliminary study. Between neurologically healthy controls and diseased children, no significant differences in T2 relaxation times could be found overall in the studied regions.

Cerebral and cerebellar greymatter atrophy in Friedreich ataxia: the IMAGE-FRDA study.

Friedreich ataxia (FRDA) is traditionally associated with neuropathology in the cerebellar dentate nucleus and spinal cord. Growing evidence also suggests involvement of the cerebral and cerebellar cortices, although reports of structural abnormalities remain mixed. This study assessed the structural integrity of cortical grey matter in FRDA, focussing on regions in which pathology may underlie themotor deficits characteristic of this disorder. T1-weighted anatomical magnetic resonance imaging scans were acquired from 31 individuals with FRDA and 37 healthy controls. Cortical thickness (FreeSurfer) and cortical volume (SPM-VBM) were measured in cerebral motor regions-of-interest (primary motor, dorsal and ventral premotor, and supplementary motor areas) alongside unconstrained exploratory analysesof the cerebral and cerebellar cortices.Correlations were assessed between cortical thickness/volume measures and each of disease severity, length of the causative genetic triplet-repeat expansion, and finger-tapping behavioural measures. Individuals with FRDA had significantly reduced cortical thickness, relative to controls, in the premotor and supplementary motor areas. Reduced cortical thickness and/or volume were also observed in the cuneus and precuneus, posterior aspects of the medial and lateral prefrontal cortices, insula,temporal poles, and cerebellar lobules V, VI, and VII. Measures of clinical severity, genetic abnormality, and motor dysfunction correlated with volume loss in the lateral cerebellar hemispheres. These results suggest that atrophy preferentially affects premotor relative to primary areasof the cortical motor system, and also extends to a range of non-motor brain regions. Furthermore, cortical thickness and cortical volume findings were largely divergent,suggesting that each is sensitive to different aspects of neuropathology in FRDA. Overall, this study supports a diseasemodel involving neural aberrations within the cerebral and cerebellar cortices, beyond those traditionally associated with this disorder.

Cerebellar neuronal loss in amyotrophic lateral sclerosis cases with ATXN2 intermediate repeat expansions

Despite evidence suggesting that the cerebellum may be targeted in amyotrophic lateral sclerosis (ALS), particularly in cases with repeat expansions in the ATXN2 and C9ORF72 genes, the integrity of cerebellar neurons has yet to be examined. The present study undertakes a histopathological analysis to assess the impact of these repeat expansions on cerebellar neurons and determine whether similar cerebellar pathology occurs in sporadic disease. Purkinje and granule cells were quantified in the vermis and lateral cerebellar hemispheres of ALS cases with repeat expansions in the ATXN2 and C9ORF72 genes, sporadic disease, and sporadic progressive muscular atrophy with only lower motor neuron degeneration. ALS cases with intermediate repeat expansions in the ATXN2 gene demonstrate a significant loss in Purkinje cells in the cerebellar vermis only. Despite ALS cases with expansions in the C9ORF72 gene having the highest burden of inclusion pathology, no neuronal loss was observed in this group. Neuronal numbers were also unchanged in sporadic ALS and sporadic PMA cases. The present study has established a selective loss of Purkinje cells in the cerebellar vermis of ALS cases with intermediate repeat expansions in the ATXN2 gene, suggesting a divergent pathogenic mechanism independent of upper and lower motor neuron degeneration in ALS. We discuss these findings in the context of large repeat expansions in ATXN2 and spinocerebellar ataxia type 2, providing evidence that intermediate repeats in ATXN2 cause significant, albeit less substantial, spinocerebellar damage compared with longer repeats in ATXN2.

Fronto-cerebellar dysfunction and dysconnectivity underlying cognition in friedreich ataxia: The IMAGE-FRDA study.

Friedreich ataxia (FRDA) is a progressive neurodegenerative disorder defined by pathology within the cerebellum and spinal tracts. Although FRDA is most readily linked to motor and sensory dysfunctions, reported impairments in working memory and executive functions indicate that abnormalities may also extend to associations regions of the cerebral cortex and/or cerebello-cerebral interactions. To test this hypothesis, 29 individuals with genetically confirmed FRDA and 34 healthy controls performed a verbal n-back working memory task while undergoing functional magnetic resonance imaging. No significant group differences were evident in task performance. However, individuals with FRDA had deficits in brain activations both in the lateral cerebellar hemispheres, principally encompassing lobule VI, and the prefrontal cortex, including regions of the anterior insular and rostrolateral prefrontal cortices. Functional connectivity between these brain regions was also impaired, supporting a putative link between primary cerebellar dysfunction and subsequent cerebral abnormalities. Disease severity and genetic markers of disease liability were correlated specifically with cerebellar dysfunction, while correlations between behavioural performance and both cerebral activations and cerebello-cerebral connectivity were observed in controls, but not in the FRDA cohort. Taken together, these findings support a diaschisis model of brain dysfunction, whereby primary disease effects in the cerebellum result in functional changes in downstream fronto-cerebellar networks. These fronto-cerebellar disturbances provide a putative biological basis for the nonmotor symptoms observed in FRDA, and reflect the consequence of localized cerebellar pathology to distributed brain function underlying higher-order cognition.

Changes in cortical, cerebellar and basal ganglia representation after comprehensive long term unilateral hand motor training

We were interested in motor performance gain after unilateral hand motor training and associated changes of cerebral and cerebellar movement representation tested with functional magnetic resonance imaging (fMRI) before and after training. Therefore, we trained the left hand of strongly right-handed healthy participants with a comprehensive training (arm ability training, AAT) over two weeks. Motor performance was tested for the trained and non-trained hand before and after the training period. Functional imaging was performed for the trained and the non-trained hand separately and comprised force modulation with the fist, sequential finger movements and a fast writing task. After the training period the performance gain of tapping movements was comparable for both hand sides, whereas the motor performance for writing showed a higher training effect for the trained hand. fMRI showed a reduction of activation in supplementary motor, dorsolateral prefrontal cortex, parietal cortical areas and lateral cerebellar areas during sequential finger movements over time. During left hand writing lateral cerebellar hemisphere also showed reduced activation, while activation of the anterior cerebellar hemisphere was increased. An initially high anterior cerebellar activation magnitude was a predictive value for high training outcome of finger tapping and visual guided movements. During the force modulation task we found increased activation in the striate.Overall, a comprehensive long-term training of the less skillful hand in healthy participants resulted in relevant motor performance improvements, as well as an intermanual learning transfer differently pronounced for the type of movement tested. Whereas cortical motor area activation decreased over time, cerebellar anterior hemisphere and striatum activity seem to represent increasing resources after long-term motor training.

Multifocal Cerebellar Liponeurocytoma

A 54-year-old female presented with a two year history of progressive headaches and upper neck pain. The headaches were worse with coughing and bending. Neurological examination was unremarkable including a normal cranial nerve examination. There was no papilloedema. A computed tomogram (CT) demonstrated a midline, posterior fossa, partly fatty, partly solid mass (Figure 1). Magnetic resonance imaging (MRI) demonstrated a mixed fatty, solid mass arising from the fourth ventricle and extending downward below the foramen magnum to the C1 level (Figure 2). The solid portions demonstrated enhancement. In addition, in the lateral right cerebellar hemisphere, there was a second, separate, solid, enhancing mass without any connection to the larger central lesion. A subtotal resection of the tumor was achieved through a suboccipital craniectomy.

The cerebellum, cognition, and behaviour

The cerebellum, cognition, and behaviour

Differential expression of genes encoding neuronal ion-channel subunits in major depression, bipolar disorder and schizophrenia: implications for pathophysiology

Evidence concerning ion-channel abnormalities in the pathophysiology of common psychiatric disorders is still limited. Given the significance of ion channels in neuronal activity, neurotransmission and neuronal plasticity we hypothesized that the expression patterns of genes encoding different ion channels may be altered in schizophrenia, bipolar and unipolar disorders. Frozen samples of striatum including the nucleus accumbens (Str-NAc) and the lateral cerebellar hemisphere of 60 brains from depressed (MDD), bipolar (BD), schizophrenic and normal subjects, obtained from the Stanley Foundation Brain Collection, were assayed. mRNA of 72 different ion-channel subunits were determined by qRT-PCR and alteration in four genes were verified by immunoblotting. In the Str-NAc the prominent change was observed in the MDD group, in which there was a significant up-regulation in genes encoding voltage-gated potassium-channel subunits. However, in the lateral cerebellar hemisphere (cerebellum), the main change was observed in schizophrenia specimens, as multiple genes encoding various ion-channel subunits were significantly down-regulated. The impaired expression of genes encoding ion channels demonstrates a disease-related neuroanatomical pattern. The alterations observed in Str-NAc of MDD may imply electrical hypo-activity of this region that could be of relevance to MDD symptoms and treatment. The robust unidirectional alteration of both excitatory and inhibitory ion channels in the cerebellum may suggests cerebellar general hypo-transcriptional activity in schizophrenia.

Regional Cerebellar Volumes Predict Functional Outcome in Children with Cerebellar Malformations

The cerebellum has recently been recognized for its role in high-order functions, including cognition, language, and behavior. Recent studies have also begun to describe a functional topography of the mature cerebellum that includes organization on a mediolateral axis. However, no study to date has examined the relationship between regional cerebellar volume and developmental disabilities in children with cerebellar malformations. The objective of this study was to estimate the extent to which total and regional cerebellar volumes are associated with developmental disabilities in a cohort of children with cerebellar malformations. Children aged 1 to 6years with a diagnosis of cerebellar malformation underwent standardized outcome measures and quantitative magnetic resonance scanning. The cerebellum was parcellated into seven mediolateral zones (three for each hemisphere plus the vermis) for regional volume analysis. In children with cerebellar malformations, decreased total cerebellar volume was associated with delays in global development, expressive language, cognition, as well as gross and fine motor function. Decreased volume in the right lateral cerebellar hemisphere was related to impaired cognition, expressive language, and gross motor function. Additionally, reduced vermis volume was associated with impaired global development, cognition, expressive language, and gross and fine motor skills, as well as behavior problems and a higher rate of positive autism spectrum screening test. These results begin to define the structural topography of functional outcome in children with cerebellar malformations and should lead to greater accuracy of prognostication as well as timely early developmental interventions.

Are Generalized Tonic–Clonic Seizures Really “Generalized”?

Cortical and Subcortical Networks in Human Secondarily Generalized Tonic–Clonic Seizures. Blumenfeld H, Varghese GI, Purcaro MJ, Motelow JE, Enev M, McNally KA, Levin AR, Hirsch LJ, Tikofsky R, Zubal IG, Paige AL, Spencer SS. Brain 2009;132(Pt 4):999–1012. Generalized tonic–clonic seizures are among the most dramatic physiological events in the nervous system. The brain regions involved during partial seizures with secondary generalization have not been thoroughly investigated in humans. We used single-photon emission computed tomography (SPECT) to image cerebral blood flow (CBF) changes in 59 secondarily generalized seizures from 53 patients. Images were analyzed using statistical parametric mapping to detect cortical and subcortical regions most commonly affected in three different time periods: 1) during the partial seizure phase prior to generalization; 2) during the generalization period; and 3) postictally. We found that in the pregeneralization period, there were focal CBF increases in the temporal lobe on group analysis, reflecting the most common region of partial seizure onset. During generalization, individual patients had focal CBF increases in variable regions of the cerebral cortex. Group analysis during generalization revealed that the most consistent increase occurred in the superior medial cerebellum, thalamus, and basal ganglia. Postictally, there was a marked progressive CBF increase in the cerebellum that spread to involve the bilateral lateral cerebellar hemispheres, as well as CBF increases in the midbrain and basal ganglia. CBF decreases were seen in the fronto-parietal association cortex, precuneus, and cingulate gyrus during and following seizures, similar to the “default mode” regions reported previously to show decreased activity in seizures and in normal behavioral tasks. Analysis of patient behavior during and following seizures showed impaired consciousness at the time of SPECT tracer injections. Correlation analysis across patients demonstrated that cerebellar CBF increases were related to increases in the upper brainstem and thalamus, and to decreases in the fronto-parietal association cortex. These results reveal a network of cortical and subcortical structures that are most consistently involved in secondarily generalized tonic–clonic seizures. Abnormal increased activity in subcortical structures (cerebellum, basal ganglia, brainstem, and thalamus), along with decreased activity in the association cortex may be crucial for motor manifestations and for impaired consciousness in tonic–clonic seizures. Understanding the networks involved in generalized tonic–clonic seizures can provide insights into mechanisms of behavioral changes, and may elucidate targets for improved therapies.

Lateral Medullary Ischemia Presenting with Persistent Hiccups and Vertigo

ABSTRACTThis study describes a patient with lateral medullary ischemia (LMI) presenting with persistent hiccups followed by vertigo with horizontal head-shaking-induced contralesional nystagmus (HSN) and discusses pertinent pathophysiology. A 65-year-old man presented with persistent hiccups and disabling spells of vertigo, lasting 30 seconds that became much more frequent and associated with lateropulsion to the right. A strong left beating HSN was evident. Magnetic resonance imaging and angiography, and intra-arterial cerebral digital subtracted angiography showed subacute ischemic lesions in the right lateral medulla and ipsilateral inferior cerebellar hemisphere, and two tight stenoses of the V1 and V4 segments of the right vertebral artery. Patient was treated by intravenous heparin and oral clopidogrel. After 48 hours, hiccups disappeared. One month later, vertigo spells were less frequent but still disabling. Endovascular stenting of the right vertebral artery stenoses was then performed. In the subsequent four years, the patient had no further episodes of hiccups or vertigo. Less intense HSN persisted. Hiccups followed by vertigo, lateropulsion, and HSN had been the clinical presentation of LMI and cerebellar ischemia, without other major neurologic or ocular motor findings. This unusual clinical variant of LMI could mimic a more benign labyrinthine lesion, and possibly leading to a dangerously delayed treatment.

Cortical and subcortical networks in human secondarily generalized tonic–clonic seizures

Generalized tonic-clonic seizures are among the most dramatic physiological events in the nervous system. The brain regions involved during partial seizures with secondary generalization have not been thoroughly investigated in humans. We used single photon emission computed tomography (SPECT) to image cerebral blood flow (CBF) changes in 59 secondarily generalized seizures from 53 patients. Images were analysed using statistical parametric mapping to detect cortical and subcortical regions most commonly affected in three different time periods: (i) during the partial seizure phase prior to generalization; (ii) during the generalization period; and (iii) post-ictally. We found that in the pre-generalization period, there were focal CBF increases in the temporal lobe on group analysis, reflecting the most common region of partial seizure onset. During generalization, individual patients had focal CBF increases in variable regions of the cerebral cortex. Group analysis during generalization revealed that the most consistent increase occurred in the superior medial cerebellum, thalamus and basal ganglia. Post-ictally, there was a marked progressive CBF increase in the cerebellum which spread to involve the bilateral lateral cerebellar hemispheres, as well as CBF increases in the midbrain and basal ganglia. CBF decreases were seen in the fronto-parietal association cortex, precuneus and cingulate gyrus during and following seizures, similar to the 'default mode' regions reported previously to show decreased activity in seizures and in normal behavioural tasks. Analysis of patient behaviour during and following seizures showed impaired consciousness at the time of SPECT tracer injections. Correlation analysis across patients demonstrated that cerebellar CBF increases were related to increases in the upper brainstem and thalamus, and to decreases in the fronto-parietal association cortex. These results reveal a network of cortical and subcortical structures that are most consistently involved in secondarily generalized tonic-clonic seizures. Abnormal increased activity in subcortical structures (cerebellum, basal ganglia, brainstem and thalamus), along with decreased activity in the association cortex may be crucial for motor manifestations and for impaired consciousness in tonic-clonic seizures. Understanding the networks involved in generalized tonic-clonic seizures can provide insights into mechanisms of behavioural changes, and may elucidate targets for improved therapies.