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Biallelic mutations in POLR3A have been associated with childhood-onset hypomyelinating leukodystrophies and adolescent-to-adult-onset spastic ataxia, the latter of which has been linked to the intronic variant c.1909 + 22G>A. We report a case of adult-onset spastic ataxia in a 75-year-old man, being a compound heterozygous carrier of this variant, whose brain and spinal cord were for the first time investigated by neuropathological examination. We describe prominent degeneration of the posterior columns, spinocerebellar tracts, and anterior corticospinal tracts of the spinal cord in a pattern resembling Friedreich's ataxia, with a notable lack of significant white matter pathology throughout the brain, in marked contrast with childhood-onset cases. Immunohistochemical examination for the POLR3A protein demonstrated no apparent differences in localization or staining intensity between the proband and an age-matched control subject. We demonstrate the clinicopathologic description of POLR3A-related neurodegenerative disease and also mention the differential diagnosis of the childhood-onset hypomyelinating leukodystrophy and late-onset spastic ataxia phenotypes.

Introduction: Cervical spondylosis means osteoarthritis of cervical spinal column. The degenerative process mainly affects the vertebrae, neural foramina and the facet joints. It leads to compression of the spinal cord resulting in progressive neural cell loss and neurological deterioration in 40 to 60 % of patients. Cervical myelopathy is a constellation of symptoms and physical findings including motor and sensory abnormalities. Spasticity and paresis are frequently seen. The patient often complaints of gait disturbance due to abnormalities incorticospinal tract and spinal spinocerebellar tracts. There is also associated loss of grip strength and finger movements. Anterior cervical discectomy and fusion (ACDF) is a commonly performed procedure to remove a herniated or degenerative disc. An incision is made in the anterior cervical region and the disc is then removed. A graft is then placed to fuse the vertebrae above and below the disc. ACDF was first described by Cloward, Smith and Robinson in 1958 and shortly later by Hirsch in 1960 who described anterior cervical decompression and debated the necessity for inter body fusion. Anterior cervical discectomy and fusion has been widely performed since the late 1950s and is currently recommended in patients in whom the nonoperative modalities for single level or multilevel disease have failed. Objectives: To study the functional outcome of cervical discectomy and fusion with anterior cervical plating among patients of cervical disc disease. Materials and Methods: 46 patients treated with ACDF with anterior cervical plating were considered in this study. Results and Conclusion: All the patients showed significant post-operative improvement in their symptoms and diagnostic scores. Thus, we can conclude that ACDF with anterior cervical plating is an efficient procedure in patients with cervical myelopathic symptoms not responding to conservative treatment.

Peripheral and intraspinal feedback is required to shape and update the output of spinal networks that execute motor behavior. We report that lumbar dI2 spinal interneurons in chicks receive synaptic input from afferents and premotor neurons. These interneurons innervate contralateral premotor networks in the lumbar and brachial spinal cord, and their ascending projections innervate the cerebellum. These findings suggest that dI2 neurons function as interneurons in local lumbar circuits, are involved in lumbo-brachial coupling, and that part of them deliver peripheral and intraspinal feedback to the cerebellum. Silencing of dI2 neurons leads to destabilized stepping in posthatching day 8 hatchlings, with occasional collapses, variable step profiles, and a wide-base walking gait, suggesting that dI2 neurons may contribute to the stabilization of the bipedal gait.

We report an autopsy case of amyotrophic lateral sclerosis with L126S mutation in the superoxide dismutase 1 (SOD1) gene (SOD1). The patient was a 69-year-old Japanese man without relevant family history, who initially presented with slow progressive muscle weakness of the lower extremities without upper motor neuron signs, and died of respiratory failure 6 years after the onset. Neuropathological examination revealed a loss of lower motor neurons and degeneration of Clarke's column commensurate with that of the posterior spinocerebellar tract and the middle root zone of the posterior column. The primary motor area was minimally affected. Characteristic SOD1-immunopositive neuronal intracytoplasmic inclusions, mixed with neurofilament accumulation, were present in the affected areas. Isolated inferior olivary hypertrophy was observed, but did not involve the contralateral dentate nucleus, or the ipsilateral red nucleus and central tegmental tract, where no neuronal inclusions were found. In combination with data from a previous autopsy case, this study suggests that the L126S mutation may cause focal neuronal degeneration in the brainstem.

One of the major impacts of spinal cord injury (SCI) is the cerebellar neurological malfunction and deformation of its sub-layers. This could be due to the enormous innervation of the spinocerebellar tract from the posterior gray horn in the spinal cord to the ipsilateral cerebellum. Although the neuroprotective role of estradiol in spinal cord (SC) injuries, as well as its ability to delay secondary cell death changes, is well-known, its effect on cerebellar layers is not fully investigated. In this study, a SCI model was achieved by injection of Kainic acid into SC of adult Male Wistar rats in order to assess the effects of SCI on the cerebellum. The animals were classified into SCI group (animals with SCI), estradiol-treated group (animals with SCI and received estradiol), control groups, and sham control group. The microscopical examination 24 h after induction of SCI revealed that KA induced the most characteristics of neurodegeneration including astrocytic propagation and microglial activation. The estradiol was injected intraperitoneally 20 min after induction of SCI, and the samples were collected at 1, 3, 7, 14, and 30 days. Histologically, the estradiol reduced the inflammatory response, enhanced the recovery of molecular, granular, and Purkinje cell layers, and therefore aided in the restoration of layer organization. These findings were also confirmed by immunohistochemical staining and gene expression profiling.

The projections from the lowest thoracic and upper lumbar (T13 to L3) segments to the cerebellar cortex were examined by anterograde tracing with biotinylated dextran amine in the rat. Unilateral injections resulted in bilateral labeling of mossy fiber terminals in lobules Ib to VI, VIII, IX and copula pyramidis. The majority (64 % of the total 30,526 labeled terminals) were present ipsilaterally in lobules II (8.5 %), III (20 %), IV (11 %), V (12 %), VIII (4.1 %), and copula pyramidis (6.8 %). The projection field in the anterior lobe was composed of five longitudinal areas: area 1 in the midline region, areas 2 and 3 in the middle and lateral parts of the vermis, and areas 4 and 5 in the medial part of the intermediate region of the hemisphere. The projection areas are characteristically localized in the apical to the middle part of the lobule. In the posterior lobe, the longitudinal areas were present in the midline region, the middle and lateral parts of lobules VIIIa and VIIIb, and the medial and middle parts of copula pyramidis. The present study reveals the whole areas and the pattern of projections from the segments containing the cells of origin of the dorsal and ventral spinocerebellar tracts.

The present study aimed to assess spinal tract formation in neurons originating from cervical (C7), brachial (C14), and thoracic (T4) regions, with the lumbar (LS2) region as a reference, in a chick embryo. For the assessment of the spinal tracts, we introduced a vector expressing human placental alkaline phosphatase into progenitor cells generated after neural tube closure and belonging to the above segments, using in ovo electroporation. The ascending axons took primarily similar paths: dorsal commissural, ventral commissural, and dorsal non-commissural paths, with some variance depending on their originating segments. Some populations of non-commissural neurons later extended their axons following a ventral path. The elongation rates of these axons are primarily constant and tended to increase over time; however, some variations depending on the originating segments were also observed. Some of the dorsally ascending axons entered into the developing cerebellum, and spinocerebellar neurons originating from T4 projected their axons into the cortex of the cerebellum differently from those from LS2. These results unveil an overall picture of early ascending spinal tract formation.

Surgical removal of lateral or ventrolateral spinal intramedullary gliomas remains a challenge. For lateral or ventrolateral tumors, the dorsal root entry zone (DREZ) myelotomy (equivalent to dorsolateral sulcus approach) and the posterior midline myelotomy would require dissection of the posterolateral tract or posterior column tracts and cause neurologic dysfunction. In Video 1, we introduce a novel approach in which myelotomy was performed anterior to DREZ. The spinal cord was entered between the DREZ and dorsal spinocerebellar tracts, and the surgical path was posterior to the lateral corticospinal tract. Thus no important spinal cord tracts were damaged. The patients with intramedullary glioma depicted in this video had no new neurologic dysfunction postoperatively. This approach has also been reported in treating intramedullary cavernous malformations.1 Compared with the DREZ approach, myelotomy anterior to the DREZ has 2 advantages. First, the blood vessels anterior to DREZ are always sparser than the posterolateral sulcus. Second, the injury of the somatosensory tract and posterior horn of the spinal cord caused by the dorsolateral sulcus approach can be avoided. Special technique details for this approach are as follows: 1) Myelotomy anterior to DREZ can be optional for selective cases of lateral or ventrolateral intramedullary tumor. 2) It is difficult for cervical intramedullary tumors because the cervical dorsal roots always cover the area of the anterior DREZ. 3) It is useful for a multisegment tumor to cut the dentate ligament. 4) Hemilaminectomy can be used in selective cases for this approach.

Cerebellar control of voluntary movements is achieved by the integration of external and internal feedback information to adjust and correct properly ongoing actions. In the forelimb of primates, rostral-spinocerebellar tract (RSCT) neurons are thought to integrate segmental, descending, and afferent sources and relay upstream a compound signal that contains both an efference copy of the spinal-level motor command and the state of the periphery. We tested this hypothesis by implanting stimulating electrodes in the superior cerebellar peduncle and recording the activity of cervical spinal neurons in primates. To dissociate motor commands and proprioceptive signals, we used a voluntary wrist task and applied external perturbations to the movement. We identified a large group of antidromically activated RSCT neurons located in deep dorsal sites and a smaller fraction of postsynaptically activated (PSA) cells located in intermediate and ventral laminae. RSCT cells received sensory input from broad, proximally biased receptive fields (RFs) and were not affected by applied wrist perturbations. PSA cells received sensory information from distal RFs and were more strongly related to active and passive movements. The anatomical and functional properties of RSCT and PSA cells suggest that descending signals converging on PSA cells contribute to both motor preparation and motor control. In parallel, RSCT neurons relay upstream an integrated signal that encodes the state of working muscles and can contribute to distal-to-proximal coordination of action. Thus the rostral spinocerebellar system sends upstream an efference copy of the motor command but does not signal abrupt errors in the performed movement. NEW & NOTEWORTHY Cerebellar coordination of voluntary movements relies on integrating feedback information to update motor output. With the use of a novel protocol, we identified spinal neurons constituting the ascending and descending components of the forelimb spinocerebellar system in behaving primates. The data suggest that descending information contributes to both motor preparation and execution, whereas ascending information conveys the spinal level motor command, such that internal and external feedback is relayed through parallel pathways.

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

Autosomal recessive ataxias (ARAs) are a heterogeneous group of inherited neurodegenerative disorders that affect the cerebellum, the spinocerebellar tract, and/or the sensory tracts of the spinal cord. This study is aimed at establishing molecular classification and phenotypic correlation of childhood-onset ARAs in Southeast Anatolia of Turkey. Sixty-five children (aged 0 to 18) from 40 unrelated families who were analyzed through hereditary ataxia NGS panel between the years of 2015–2018 were selected for the study. Seventeen different, clinically significant ARA-related pathogenic variants were detected in 33 of 40 families (82.5%), 12 of which were noted to be unreported variants. Among these 33 families, 24 had ATM-related (72.72%), four had SACS-related (12.12%), three had COQ8A-related (9.09%), and two had APTX-related (6.06%) pathogenic variants. The c.3576G>A (p.K1192=) was the most common homozygous pathogenic ATM variant (33.33%) that was associated with milder phenotype of ataxia telangiectasia (AT) with the onset of age of 3. Patients with SACS variants demonstrated developmental delay and progressive ataxia before the age of 3. Slowly progressive ataxia and intellectual disability were the common clinical manifestations of the patients with homozygous c.1396delG (p. E466Rfs*11) pathogenic variant in COQ8A. Homozygous APTX c.689T>G (p.V230G) pathogenic variant was identified in two patients who had chief complaint of ataxic gait onset after puberty. The most common types of ARAs in this region are AT- and Charlevoix-Saguenay-type spastic ataxia. ATM gene analysis should be performed foremost on children presenting early-onset ataxia from Southeastern Anatolia. If there is a concomitant peripheral neuron involvement, SACS gene analysis should be preferred. This valuable data will be a guide for the first step molecular diagnostic approach before requesting the NGS panel for ARA.

SUMMARY Coordinated motor behaviors depend on feedback communication between peripheral sensory systems and central circuits in the brain and spinal cord. Relay of muscle- and tendon-derived sensory information to the CNS is facilitated by functionally and anatomically diverse groups of spinocerebellar tract neurons (SCTNs), but the molecular logic by which SCTN diversity and connectivity is achieved is poorly understood. We used single-cell RNA sequencing and genetic manipulations to define the mechanisms governing the molecular profile and organization of SCTN subtypes. We found that SCTNs relaying proprioceptive sensory information from limb and axial muscles are generated through segmentally restricted actions of specific Hox genes. Loss of Hox function disrupts SCTN-subtype-specific transcriptional programs, leading to defects in the connections between proprioceptive sensory neurons, SCTNs, and the cerebellum. These results indicate that Hox-dependent genetic programs play essential roles in the assembly of neural circuits necessary for communication between the brain and spinal cord., Graphical Abstract, In Brief Baek et al. show that Hox-transcription factor-dependent programs govern the specification and connectivity of spinal interneurons that relay muscle-derived sensory information to the cerebellum. These findings shed light on the development of neural circuits required for proprioception—the perception of body position.

A Corriedale ewe was confirmed as the first atypical scrapie case during an active surveillance program for transmissible spongiform encephalopathies in small ruminants in Japan. The animal was homozygous for the AF141RQ haplotype of PRNP. The animal showed clinical neurological signs possibly due to listeriosis before culling. Western blot analysis showed an unusual multiple banded pattern with a low-molecular fragment at ~7 kDa. Histopathology revealed suppurative meningoencephalitis caused by listeriosis in the brainstem. Fine granular to globular immunostaining of disease-associated prion proteins was mainly detected in the neuropil of the spinal tract of the trigeminal nerve and in the white matter of the spinocerebellar tract. Based on these results, this case was conclusively diagnosed as atypical scrapie with encephalitic listeriosis.

Ataxia is a neurodegenerative disease resulting from brainstem, cerebellar, and/or spinocerebellar tracts impairments. Symptoms onset could vary widely from childhood to late-adulthood. Autosomal cerebellar ataxias are considered as one of the most complex group in neurogenetics. In addition to their genetic heterogeneity, there is an important phenotypic variability in the expression of cerebellar impairment, complicating the genetic mutation research. A pattern recognition approach using brain MRI measures of atrophy, hyperintensities and iron-induced hypointensity of the dentate nuclei, could be therefore helpful in guiding genetic research. This review will discuss a pattern recognition approach that, associated with the age at disease onset, and clinical manifestations, may help neuroradiologists differentiate the most frequent profiles of ataxia.

Background and purpose Gerstmann-Straussler-Scheinker syndrome is a rare hereditary neurodegenerative disorder with clinical heterogeneity. This study is aim to demonstrate the clinical spectrum and radiologic characteristics of patients caused by Pro102Leu mutation in PRNP. Materials and methods We retrospect clinical manifestations of five patients from four Japanese families, and comprehensively analyzed their brain MRI, SPECT (N-isopropyl-p-[123I] iodoamphetamine), and PET (18F-2-fluoro-2-deoxy- d -glucose) images. Results All patients developed ataxia of lower limbs and trunk, gait disturbance, dysesthesia in legs, and lower limb hyporeflexia. In the early clinical stage before dementia began, no noticeable abnormalities could be observed from brain MRI, but SPECT and PET revealed mosaic-like pattern of blood flow and glucose metabolism of the brain. Predominant abnormalities were found in the occipital and frontal lobes on SPECT and PET analysis, respectively. In SPECT analysis, blood flow of the anterior cerebellar lobes was lower than that of the posterior cerebellar lobes. Conclusions Clinical symptoms resulting from failure of dorsal horn of spinal cord and spinocerebellar tracts were observed in all cases. Radiologic findings revealed individual differences of involved region in their brain, which could produce clinical diversity. We identified a downtrend of blood flow in the anterior cerebellar lobes, a projection field of the spinocerebellar tracts, which is an important feature of Gerstmann-Straussler-Scheinker syndrome.

We previously showed that proprioceptive sensory input from the hindlimbs to the anterior cerebellar cortex of the cat may not be simply organized with respect to a body map, but it may also be distributed to multiple discrete functional areas extending beyond classical body map boundaries. With passive hindlimb stepping movements, cerebellar activity was shown to relate to whole limb kinematics as does the activity of dorsal spinocerebellar tract (DSCT) neurons. For DSCT activity, whole limb kinematics provides a solid functional framework within which information about limb forces, such as those generated during active stepping, may also be embedded. In this study, we investigated this idea for the spinocerebellar cortex activity by examining the activity of cerebellar cortical neurons during both passive bipedal hindlimb stepping and active stepping on a treadmill. Our results showed a functional compartmentalization of cerebellar responses to hindlimb stepping movements depending on the two types of stepping and strong relationships between neural activities and limb axis kinematics during both. In fact, responses to passive and active stepping were generally different, but in both cases their waveforms were related strongly to the limb axis kinematics. That is, the different stepping conditions modified the kinematics representation without producing different components in the response waveforms. In sum, cerebellar activity was consistent with a global kinematics framework serving as a basis upon which detailed information about limb mechanics and/or about individual limb segments might be imposed.

Muscle kinematics and kinetics are nonlinearly encoded by proprioceptors, and the changes in muscle length and velocity are integrated into Ia afferent. Besides, proprioceptive signals from multiple muscles are probably mixed in afferent pathways, which all lead to difficulties in proprioceptive recognition for the cerebellum. In this study, the artificial neural networks, whose organizations are biologically based on the spinocerebellar tract and cerebellum, are utilized to decode the proprioceptive signals. Consistent with the controversy of the proprioceptive division in the dorsal spinocerebellar tract, the spinocerebellar tract networks incorporated two distinct inferences, (1) the centralized networks, which mixed Ia, II, and Ib and processed them together; (2) the decentralized networks, which processed Ia, II, and Ib afferents separately. The cerebellar networks were based on the Marr–Albus model to recognize the kinematic states. The networks were trained by a specific movement, and the trained networks were subsequently required to predict kinematic states of six movements. The results demonstrated that the centralized networks, which were more consistent with the physiological findings in recent years, had better recognition accuracy than the decentralized networks, and the networks were still effective even when proprioceptive afferents from multiple muscles were integrated.

Background Spinocerebellar ataxia type 1 (SCA1) belongs to polyglutamine CAG repeat neurodegenerative disorders involving principally the cerebellum, brainstem and spinocerebellar tracts. One of the dominating symptoms is a postural disequilibrium. As there is need of biomarkers to follow the natural course of SCA we aimed to assess the progression of balance impairments by static posturography. Methods The subjects were: 26 symptomatic SCA1 patients (aged 39.2 ± 12.4 years, CAG 50.7 ± 6.3) with mean disease duration 5.5 ± 5.1 and 38 age- and gender- matched healthy controls (HC). They underwent static posturography during 5 years of observation. The movements of the center of feet pressure (COP) during quiet standing with eyes open (EO) and closed (EC) were evaluated by calculation of: mean radius, developed surface area and COP movement velocity. Severity of ataxia was evaluated with Scale for Assessment and Rating of Ataxia (SARA). Results All the COP sway measures have differed statistically significant from HC (p Conclusions Our study confirmed that quantitative posturography reflects objectively progression of postural disequilibrium in patients with ataxia. It might be a useful biomarker in the future therapeutic trials.

A 64-year-old man noticed weakness in his arms and dyspnea upon exertion. Four months later he was admitted to our hospital, where muscle atrophy and hyperactive deep tendon reflexes in the arms were observed upon examination. A needle electromyograph study revealed acute and chronic denervation in the extremities, and he was diagnosed as having amyotrophic lateral sclerosis (ALS). Seven months after onset of the disease, he died of respiratory failure. Neuropathologically, neuronal cell loss was observed in the motor cortex, hypoglossal nuclei, cervical and lumbar anterior horns and Clarke's nuclei. Some of the remaining neurons contained neurofilamentous conglomerate inclusions (CIs). A small number of Lewy body-like hyaline inclusions (LBHIs) were also observed. No the Bunina bodies, skein-like inclusions or basophilic inclusions were detectable. Tract degeneration was moderate in the dorsal and ventral spinocerebellar tracts, mild in the pyramidal tract, but not discerned in the posterior column. Immunohistochemical examinations revealed that the CIs were strongly positive for phosphorylated neurofilament and moderately positive for ubiquitin and Cu/Zn superoxide dismutase 1 (SOD1). Moreover, a number of phosphorylated tau protein-positive globose neurofibrillary tangles (NFTs) and threads were observed in the periaqueductal gray matter, oculomotor nuclei and trochlear nuclei. Although the family history was negative for neuromuscular diseases, the neuropathological findings indicated features of familial ALS with a SOD1 mutation. In fact, DNA analysis of frozen-brain tissue revealed the presence of the I113T SOD1 mutation. This case represents the first one of this mutation in a patient who showed CIs as well as LBHIs in the motor neurons at the same time, in addition to the NFTs in the mesencephalic tegmentum.

The main objective of this review is to re-examine the type of information transmitted by the dorsal and ventral spinocerebellar tracts (DSCT and VSCT respectively) during rhythmic motor actions such as locomotion. Based on experiments in the 1960s and 1970s, the DSCT was viewed as a relay of peripheral sensory input to the cerebellum in general, and during rhythmic movements such as locomotion and scratch. In contrast, the VSCT was seen as conveying a copy of the output of spinal neuronal circuitry, including those circuits generating rhythmic motor activity (the spinal central pattern generator, CPG). Emerging anatomical and electrophysiological information on the putative subpopulations of DSCT and VSCT neurons suggest differentiated functions for some of the subpopulations. Multiple lines of evidence support the notion that sensory input is not the only source driving DSCT neurons and, overall, there is a greater similarity between DSCT and VSCT activity than previously acknowledged. Indeed the majority of DSCT cells can be driven by spinal CPGs for locomotion and scratch without phasic sensory input. It thus seems natural to propose the possibility that CPG input to some of these neurons may contribute to distinguishing sensory inputs that are a consequence of the active locomotion from those resulting from perturbations in the external world.

The crossed spinocerebellar tracts originate from neurons in the basolateral part of lamina V, the sacral nuclei of Stilling and the ventrolateral part of the ventral horn of the L6 to caudal segments. The present study examined their projection areas in the cerebellar cortex by using anterograde labeling of mossy fiber terminals with biotinylated dextran in the rat. Labeled terminals were distributed bilaterally in lobules I–V of the anterior lobe. They were most abundant in the apical parts of the lateral vermis and the intermediate region of lobules Ib and IIa, and the rostral side of lobule IIb. The number of labeled terminals in lobules Ib-IIb accounted for 56% and 81%, respectively, of the total 9783 and 7045 labeled terminals. The number of labeled terminals decreased in lobules III to V. In the posterior lobe labeled terminals were distributed exclusively to lobules VIIIa and VIIIb and copula pyramidis. The present study demonstrates that spinocerebellar neurons of the sacral-caudal segments project primarily to the lateral part of lobules I and II, and less densely to lobules III–V and VIII, and copula pyramidis. The projection pattern was essentially similar to that observed in the cat.

Intraoperative neurophysiological monitoring has become a routine procedure in complex spine surgery. Somatosensory-evoked potential (SSEP) recording has been advocated to monitor the functional integrity of the nervous system during surgical manipulation. When stimulated, sensory afferents give rise to signals carried via the dorsal columns (DCs) within the spinal cord to the medial lemniscus and spinocerebellar tracts, ending in the primary somatosensory cortex. SSEP monitoring does not involve the motor pathways, which in some clinical situations can lead to false-negative results and postoperative neurological deficits undetected intraoperatively. Dermatomal SSEP testing allows for assessment of individual nerve roots during surgery and has been shown to be more sensitive. However, the sensitivity and specificity of this method varies and is inferior to electromyographic (EMG) monitoring. EMG has become the standard of practice in complex spine surgery, providing surgeons with accurate feedback about individual nerve root activity during surgical manipulation of neural structures and the presence of malpositioned screws.

Although the cerebellum participates in many different functions, its coordinating role in learning and execution of movements remains its most visible aspect to our behavior. Multiple pathways convey information from the body to the cerebellum. These spinal pathways can be divided in systems that, either directly or indirectly, enter the cerebellar cortex to terminate as mossy fibers and in pathways that reach the cerebellum by way of the inferior olive and as a consequence will terminate as climbing fibers. Cerebellar processing is also mediated to the spinal cord by a multitude of routes. Corticospinal, rubrospinal, tectospinal, vestibulospinal and reticulospinal tracts may all, at least to some extent, be controlled by cerebellar output.

Spinocerebellar tract neurons are inhibited by various sources of input via pathways activated by descending tracts as well as peripheral afferents. Inhibition may be used to modulate transmission of excitatory information forwarded to the cerebellum. However it may also provide information on the degree of inhibition of motoneurons and on the operation of inhibitory premotor neurons. Our aim was to extend previous comparisons of morphological substrates of excitation of spinocerebellar neurons to inhibitory input. Contacts formed by inhibitory axon terminals were characterised as either GABAergic, glycinergic or both GABAergic/glycinergic by using antibodies against vesicular GABA transporter, glutamic acid decarboxylase and gephyrin. Quantitative analysis revealed the presence of much higher proportions of inhibitory contacts when compared with excitatory contacts on spinal border (SB) neurons. However similar proportions of inhibitory and excitatory contacts were associated with ventral spinocerebellar tract (VSCT) and dorsal spinocerebellar tract neurons located in Clarke's column (ccDSCT) and the dorsal horn (dhDSCT). In all of the cells, the majority of inhibitory terminals were glycinergic. The density of contacts was higher on somata and proximal versus distal dendrites of SB and VSCT neurons but more evenly distributed in ccDSCT and dhDSCT neurons. Variations in the density and distribution of inhibitory contacts found in this study may reflect differences in information on inhibitory processes forwarded by subtypes of spinocerebellar tract neurons to the cerebellum.

The cerebellum receives information from the hindlimbs through several populations of spinocerebellar tract neurons. Although the role of these neurons has been established in electrophysiological experiments, the relative contribution of afferent fibres and central neurons to their excitatory input has only been estimated approximately so far. Taking advantage of differences in the immunohistochemistry of glutamatergic terminals of peripheral afferents and of central neurons (with vesicular glutamate transporters VGLUT1 or VGLUT2, respectively), we compared sources of excitatory input to four populations of spinocerebellar neurons in the thoraco-lumbar spinal cord: dorsal spinocerebellar tract neurons located in Clarke's column (ccDSCT) and in the dorsal horn (dhDSCT) and ventral spinocerebellar tract (VSCT) neurons including spinal border (SB) neurons. This was done on 22 electrophysiologically identified intracellularly labelled neurons in cats and on 80 neurons labelled by retrograde transport of cholera toxin b subunit injected into the cerebellum of rats. In both species distribution of antibodies against VGLUT1 and VGLUT2 on SB neurons (which have dominating inhibitory input from limb muscles), revealed very few VGLUT1 contacts and remarkably high numbers of VGLUT2 contacts. In VSCT neurons with excitatory afferent input, the number of VGLUT1 contacts was relatively high although VGLUT2 contacts likewise dominated, while the proportions of VGLUT1 and VGLUT2 immunoreactive terminals were the reverse on the two populations of DSCT neurons. These findings provide morphological evidence that SB neurons principally receive excitatory inputs from central neurons and provide the cerebellum with information regarding central neuronal activity.

The aim in this study is to elucidate the laterality of chicken spinocerebellar (SC) neurons that originate from the caudal cervical to caudal lumbosacral spinal cord. SC neurons in the spinal segment (SS) 17-20 consisted of a mixture of crossed and uncrossed axons. SC neurons in the more cranial and caudal SS than SS 17-20 (transitional zone) were generally uncrossed and crossed, respectively. In the transitional zone, SC neurons in spinal border cells and ventral border cells of the ventral horn changed dramatically from an uncrossed to a crossed type between SS 17 and SS 18. Chicken SC neurons are markedly different in laterality from mammalian SC neurons.

It has previously been established that ventral spinocerebellar tract (VSCT) neurons and dorsal spinocerebellar tract neurons located in Clarke's column (CC DSCT neurons) forward information on actions of premotor interneurons in reflex pathways from muscle afferents on α-motoneurons. Whether DSCT neurons located in the dorsal horn (dh DSCT neurons) and spinocervical tract (SCT) neurons are involved in forwarding similar feedback information has not yet been investigated. The aim of the present study was therefore to examine the input from premotor interneurons to these neurons. Electrical stimuli were applied within major hindlimb motor nuclei to activate axon-collaterals of interneurons projecting to these nuclei, and intracellular records were obtained from dh DSCT and SCT neurons. Direct actions of the stimulated interneurons were differentiated from indirect actions by latencies of postsynaptic potentials evoked by intraspinal stimuli and by the absence or presence of temporal facilitation. Direct actions of premotor interneurons were found in a smaller proportion of dh DSCT than of CC DSCT neurons. However, they were evoked by both excitatory and inhibitory interneurons, whereas only inhibitory premotor interneurons were previously found to affect CC DSCT neurons [as indicated by monosynaptic excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) in dh DSCT and only IPSPs in CC DSCT neurons]. No effects of premotor interneurons were found in SCT neurons, since monosynaptic EPSPs or IPSPs were only evoked in them by stimuli applied outside motor nuclei. The study thus reveals a considerable differentiation of feedback information provided by different populations of ascending tract neurons.

Neural circuits are organized into complex topographic maps. Although several neuroanatomical and genetic tools are available for studying circuit architecture, a limited number of methods exist for reliably revealing the global patterning of multiple topographic projections. Here we used wheat germ agglutinin (WGA) conjugated to Alexa 555 and 488 for dual color fluorescent mapping of parasagittal spinocerebellar topography in three dimensions. Using tissue section and wholemount imaging we show that WGA-Alexa tracers have three main characteristics that make them ideal tools for analyses of neural projection topography. First, the intense brightness of Alexa fluorophores allows multi-color imaging of patterned afferent projections in wholemount preparations. Second, WGA-Alexa tracers robustly label the entire trajectory of developing and adult projections. Third, long tracts such as the adult spinocerebellar tract can be traced in less than 6 h. Moreover, using WGA-Alexa tracers we resolved a level of complexity in the compartmentalized topography of the spinocerebellar projection map that has never before been appreciated. In summary, we introduce versatile tracers for rapidly labeling multiple topographic projections in three dimensions and uncover wiring complexities in the spinocerebellar map.

Inherited cerebellar ataxias constitute a complicated and heterogeneous group of neurodegenerative disorders affecting the cerebellum and/or spinocerebellar tract, spinal cord and peripheral nerves. A peripheral neuropathy is frequently seen in inherited cerebellar ataxias although it rarely reveals the disease. Moreover, the peripheral neuropathy is helpful for the diagnostic procedure and contributes to the functional prognosis of the disease. Thus, electroneuromyography is essential in the algorithm for the diagnosis of inherited cerebellar ataxias, as well as brain MRI (looking especially for cerebellar atrophy) and the assessment of several biomarkers (alpha-foetoprotein, vitamin E, albumin, LDL cholesterol, lactic acid, phytanic acid).

Mutations in the fused in sarcoma gene (FUS) were recently found in patients with familial amyotrophic lateral sclerosis (ALS). The present study aimed to clarify unique features of familial ALS caused by FUS mutation in the Japanese population. We carried out clinical, neuropathological, and genetic studies on a large Japanese pedigree with familial ALS. In six successive generations of this family, 16 individuals of both sexes were affected by progressive muscle atrophy and weakness, indicating an autosomal dominant trait. Neurological examination of six patients revealed an age at onset of 48.2 ± 8.1 years in fourth generation patients, while it was 31 and 20 years in fifth and sixth generation patients, respectively. Motor paralysis progressed rapidly in these patients, culminating in respiratory failure within 1 year. The missense mutation c.1561 C>T (p.R521C) was found in exon 15 of FUS in the four patients examined. Neuropathological study of one autopsied case with the FUS mutation revealed multiple system degeneration in addition to upper and lower motor neuron involvement: the globus pallidus, thalamus, substantia nigra, cerebellum, inferior olivary nucleus, solitary nucleus, intermediolateral horn, Clarke’s column, Onuf’s nucleus, central tegmental tract, medial lemniscus, medial longitudinal fasciculus, superior cerebellar peduncle, posterior column, and spinocerebellar tract were all degenerated. Argyrophilic and basophilic neuronal or glial cytoplasmic inclusions immunoreactive for FUS, GRP78/BiP, p62, and ubiquitin were detected in affected lesions. The FUS R521C mutation in this Japanese family caused familial ALS with pathological features of multiple system degeneration and neuronal basophilic inclusions.

Literature highlights that serotonergic descending pathways [14] are implicated in somatosensory functions in the spinal cord and that serotonin (5-HT) in the dorsal horn might play a role in motor function through proprioceptive feedback [3, 8, 9, 13]. We hypothesized that 5-HT release in dorsal horn might represent an important factor in the completion of locomotion by facilitation of the spinocerebellar tract [8] and/or by modulation of spinal reflex pathways [9]. The present study demonstrates that during locomotor activity, 5-HT is released in layers II, III, IV, V of Rexed laminae. Microdialysis in combination with HPLC was used to measure concentrations of neurotransmitters in the lumbar dorsal horn before, during, and after a treadmill running exercise. Our results show a significant 41% increase of 5-HT release within the dorsal horn during a running exercise. 5-HT release is temporally related to exercise. The present study demonstrates that dorsal horn 5-HT release might modulate locomotion.