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The topodiagnostic implications of hemiataxia following lesions of the human brainstem are only incompletely understood. We performed a voxel-based statistical analysis of lesions documented on standardised MRI in 49 prospectively recruited patients with acute hemiataxia due to isolated unilateral brainstem infarction. For statistical analysis individual MRI lesions were normalised and imported in a three-dimensional voxel-based anatomical model of the human brainstem. Statistical analysis revealed hemiataxia to be associated with lesions of three distinct brainstem areas. The strongest correlation referred to ipsilateral rostral and dorsolateral medullary infarcts affecting the inferior cerebellar peduncle, and the dorsal and ventral spinocerebellar tracts. Secondly, lesions of the ventral pontine base resulted in contralateral limb ataxia, especially when ataxia was accompanied by motor hemiparesis. In patients with bilateral hemiataxia, lesions were located in a paramedian region between the upper pons and lower midbrain, involving the decussation of dentato-rubro-thalamic tracts. We conclude that ataxia following brainstem infarction may reflect three different pathophysiological mechanisms. (1) Ipsilateral hemiataxia following dorsolateral medullary infarctions results from a lesion of the dorsal spinocerebellar tract and the inferior cerebellar peduncle conveying afferent information from the ipsilateral arm and leg. (2) Pontine lesions cause contralateral and not bilateral ataxia presumably due to major damage to the descending corticopontine projections and pontine base nuclei, while already crossed pontocerebellar fibres are not completely interrupted. (3) Finally, bilateral ataxia probably reflects a lesion of cerebellar outflow on a central, rostral pontomesencephalic level.

Ataxias are heterogeneous disorders characterized by impaired coordination in voluntary movements. They are more frequently caused by degeneration of cerebellar structures and spinocerebellar tracts.

This chapter provides a detailed account of the major ascending tracts which carries information to higher centers within the brain. It will discuss the dorsal column/medial lemnsicus system via the gracile and cuneate fasciculi, the spinocerebellar tract and the various components of the anterolateral system. It will systematically describe the lateral and ventral spinothalamic tracts as well as the spinohypothalamic, spinoreticular, spinotectal (spinomesencephalic) and spino-olivary tracts. Summary tables will provide easy to access information about key points. Where relevant, clinical examination will be detailed, and also common pathologies which can affect these tract systems.

In comparison with the lateral (Wallenberg), medial (Dejerine) and hemimedullary (Reinhold) medulla oblongata syndromes, the Babinski-Nageotte and Cestan-Chenais syndromes are much less familiar cerebrovascular disorders. While the Babinski-Nageotte syndrome is usually confused with the hemimedullary syndrome, reports of the extremely rare Cestan-Chenais syndrome are missing from the modern neurological literature. The pathological and magnetic resonance imaging (MRI) correlations of the Cestan-Chenais syndrome have not been shown so far. We compared clinical and MRI features of two patients exhibiting classical Babinski-Nageotte and Cestan-Chenais syndromes according to their original descriptions with those of three patients with lateral, medial and hemimedullary syndromes. Our study shows that Babinski-Nageotte syndrome includes all symptoms of the Wallenberg syndrome and additionally contralateral hemiparesis due to a spreading of the "Wallenbergian" lateral lesion to the pyramidal tract. The Cestan-Chenais syndrome includes all symptoms of the Babinski-Nageotte syndrome with the exception of the ipsilateral cerebellary hemiataxia because of sparing of the posterior spinocerebellar tract. The Babinski-Nageotte syndrome is neither clinically nor on MRI identical with hemimedullary syndrome. Hypoglossal palsy, an invariable symptom of hemimedullary lesion is not part of the Babinski-Nageotte syndrome. The contralateral hypesthesia is dissociated in the Babinski-Nageotte syndrome. The Babinski-Nageotte and Cestan-Chenais syndromes are intermediolateral medullary syndromes with all (Babinski-Nageotte) or nearly all (Cestan-Chenais) features of the lateral and some features of the medial medulla oblongata syndromes.

The dorso-lateral medullary syndrome (Wallenberg's syndrome) is produced by infarction of a wedge of lateral medulla posterior to the inferior olivary nucleus and is usually caused by vertebral artery occlusion. Ipsilateral axial lateropulsion as an initial symptom of vertebral artery occlusion is rather rare and the anatomical structure responsible is still uncertain. Here we describe two patients presenting with ipsilateral axial lateropulsion as an initial symptom of vertebral artery occlusion. In one the stroke affected the dorso-lateral aspect of the medulla, in the other more lateral aspects of the medulla were involved. Our data suggest that ipsilateral axial lateropulsion may be caused by lesions of different topography involving either the vestibular nuclei, the cerebellar peduncle or the spinocerebellar tracts.

In lumbosacral segments the spinal cord of birds contains numerous paragriseal neurons lying in the white matter of lateral and ventral funiculus. These paragriseal cells project to the cerebellum. Neurons of the dorsal horn (mainly Clarke's column) make up a dorsal spinocerebellar tract and neurons of the ventral horn (mainly spinal border cells) are at the origin of a ventral spinocerebellar tract. It was the aim of this investigation to look for the distribution of spinocerebellar ventral horn neurons and paragriseal cells in the thoracolumbosacral spinal cord of pigeons and to compare this distribution with that of the cervical enlargement. Neuroanatomical tracers were injected into the anterior cerebellum of pigeons and labeled spinal neurons were counted throughout the length of the spinal cord. In the cervical enlargement the number of spinocerebellar ventral horn neurons increases more rostral than that of dorsal horn neurons but the number of both groups of neurons decreases simultaneously at the caudal end of the enlargement. In the ventral horn of thoracolumbosacral segments the number of spinocerebellar ventral horn neurons and paragriseal cells increases again more rostrally than that of dorsal horn cells. However, the number of ventral horn cells decreases whereas that of paragriseal cells and of dorsal horn cells is maintained. This shows that the number of ventral horn cells decreases in favor of paragriseal cells, which supports the suggestion that paragriseal cells are displaced ventral horn spinocerebellar neurons. It is discussed whether the paragriseal neurons migrate toward their input.

Neuropathology of a case of Shiga pedigree with proximal-dominant hereditary motor and sensory neuropathy (HMSN-P) is reported. In the spinal cord, marked atrophy of anterior and posterior roots was found. Histologically, severe neuronal loss and gliosis were evident in the spinal anterior horns. Bunina bodies and hyaline inclusions were not seen. Neuronal loss and gliosis were mild in the hypoglossal and facial nuclei. Myelin pallor was evident in the posterior and lateral columns of the spinal cord. The posterior column, corticospinal tract and spinocerebellar tract showed loss of myelinated fibres and gliosis. In Clarke's nucleus, neuronal loss and gliosis were found. Dorsal root ganglion showed mild neuronal loss with a few Nageotte's nodules. In the precentral gyrus, mild loss of Betz cells and gliosis together with neurophagia were observed. In the iliopsoas muscle, islands of isolated muscle fibres can be seen against a background of fatty tissue. The sural nerve showed a markedly decreased number of large and small myelinated fibres without onion-bulb formation. Small infarctions were seen in the subcortical white matter, the basal ganglia, the brainstem and the cerebellum. Immunohistochemistry revealed ubiquitin-positive, TAR DNA-binding 43 kDa-positive, TFG-positive inclusions in the remaining LMNs.

Peripheral nerve-evoked potentials recorded in the cerebellum 35 yr ago inferred that sensory transmission via the dorsal spinocerebellar tract (DSCT) is reduced occasionally and only during eye movements of active sleep compared with wakefulness or quiet sleep. A reduction or withdrawal of primary afferent input and/or ongoing inhibition of individual lumbar DSCT neurons may underlie this occurrence. This study distinguished between these possibilities by examining whether peripheral nerve-evoked responses recorded from individual DSCT neurons are suppressed specifically during active sleep, and if so, whether GABA mediates this phenomenon. Synaptic responses to threshold stimuli applied to the sciatic nerve were characterized by a single spike response at short latency and/or a longer latency burst of action potentials. During the state of quiet wakefulness, response magnitude did not differ from that observed during quiet sleep. During active sleep, short and long latency responses were suppressed by 26 and 14%, respectively, and returned to pre-active sleep levels following awakening from active sleep. Sciatic nerve-evoked early and late responses were further analyzed in a paired fashion around computer-tagged eye movement events that hallmark the state of active sleep. Response magnitude was suppressed by 14.4 and 11.5%, respectively, during eye movement events of active sleep. The GABAA antagonist bicuculline, applied juxtacellularly by microiontophoresis, abolished response suppression during non–eye movement periods and eye movement events of active sleep. In conclusion, synaptic transmission via DSCT neurons is inhibited by GABA tonically during non–eye movement periods and phasically during eye movement events of active sleep.

In myelopathy, unilateral compression of the spinal cord in cases of disc herniation would be expected to produce Brown-Séquard syndrome. However, a transverse lesion syndrome occurs in most clinical cases. In order to reveal the mechanism by which unilateral compression induces transverse damage to the spinal cord, damage of the gray and white matter in each half of the spinal cord were evaluated quantitatively to determine the density of GFAP-positive astrocytes. The cervical spinal cord in rabbits was unilaterally compressed with a small screw. The area of each half of the damaged cord and the density of GFAP-positive astrocytes of the compressed and contralateral halves were investigated one week after the surgery. No apparent paralysis was observed during the period of observation. As the compression increased, the area of the compressed half of the spinal cord decreased significantly compared to the contralateral half. The densities of GFAP-positive astrocytes in the gray matter and the anterior funiculus increased significantly in the compressed half. There were no significant differences in the densities at the lateral and dorsal funiculi between the compressed and contralateral halves. The tissue damage in the gray matter of the compressed half was markedly higher. No significant difference between the two halves in damage was seen in the lateral funiculus, where in the lateral pyramidal and the dorsal spinocerebellar tracts are found. These findings provide evidence of the mechanistic basis for the spinal cord damage that leads to transverse lesion syndrome in unilateral compression myelopathy.

A quantitative analytical method was used to measure myelinated axon morphometric parameters (e.g., axon area, ratio of axon area/fiber area, and index of circularity) in rat nervous tissue during intoxication with 2,5-hexanedione (HD). Parameters were assessed in nerve roots (dorsal and ventral) and in ascending (gracile fasciculus and spinocerebellar tract) and descending (corticospinal and rubrospinal tracts) spinal cord white matter tracts (L4-L5) of rats intoxicated with HD at two different daily dose-rates (175 or 400 mg HD/kg/day, gavage). For each dose-rate, tissue was sampled at four neurological endpoints: unaffected, slight, moderate, and severe toxicity, as determined by gait analysis and measurements of grip strength. Results indicate that, regardless of the HD dose-rate, axon atrophy (reduced axon area) was a widespread, abundant effect that developed in concert with neurological deficits. The atrophy response occurred contemporaneously in both ascending and descending spinal tracts, which suggests that loss of caliber developed simultaneously along the proximodistal axon axis. In contrast, swollen axons were a numerically small component and were present in nerve roots and spinal tracts only during subchronic intoxication at the lower HD dose-rate (i.e., 175 mg/kg/day). Intoxication at the higher dose-rate (400 mg/kg/day) produced neurological deficits in the absence of axonal swellings. These observations in conjunction with our previous studies of HD-induced peripheral neuropathy (Toxicol. Appl. Pharmacol. 135 (1995) 58; and Toxicol. Appl. Pharmacol. 165 (2000) 127) indicate that axon atrophy, and not axonal swelling, is a primary neuropathic phenomenon.

Cells in the main cuneate nucleus (MCN) are known to provide a direct projection to the cerebellum, but the precise nature of the information these cells transmit to the cerebellum is unknown. The present study employed anatomical and electrophysiological procedures to determine the location of cuneocerebellar cells in the MCN, and their somatosensory properties in the rat. The location of neurones projecting to the cerebellum was determined with injections of the retrograde tracers, horseradish peroxidase or Fluoro-Gold in vermal and paravermal regions of the cerebellum. Topographically, the majority of retrogradely labelled cells in the MCN were found to lie primarily ventrolateral in the nucleus and rostral to the level of the obex. Single unit recordings from 69 well characterized MCN cells, identified as projection cells by antidromic activation from stimulation of the inferior cerebellar peduncle, were classified according to their responses to cutaneous stimulation and manipulation of joints and muscles. A slight majority of cells (37.7%) responded only to manipulation/stimulation of joints, and 30.4% of cells responded only to cutaneous stimulation. The remaining cells received convergent input from joint and cutaneous receptors. Cutaneous responsive cells all rapidly adapted to maintained stimuli, and had large receptive fields (RFs) that were generally located over the joints. These cells could be activated by passive movements of the forelimb that deformed the RF. They only discharged during movements and were silent during maintained limb positions. Cells responsive to punctate mechanical stimuli applied to the joint capsules, responded to passive movements of the forelimb, but typically only discharged towards the limits of joint movement, and adapted within a few seconds. Once adapted, small perturbations of joint position resulted in vigorous dynamic responses. The results indicate that the neurones in the MCN of the rat which project directly to the cerebellum are localized in the rostral half of the nucleus. They transmit predominantly dynamic information from joint and cutaneous receptors that are likely to be normally activated as a result of limb movements. These cells could signal information about evolving movements or disturbances of forelimb posture or stance.

Background Most of what is known regarding the actions of injectable barbiturate anesthetics on the activity of lumbar sensory neurons arises from experiments performed in acute animal preparations that are exposed to invasive surgery and neural depression caused by coadministered inhalational anesthetics. Other parameters such as cortical synchronization and motor ouflow are typically not monitored, and, therefore, anesthetic actions on multiple cellular systems have not been quantitatively compared. Methods The activities of antidromically identified dorsal spinocerebellar and spinoreticular tract neurons, neck motoneurons, and cortical neurons were monitored extracellularly before, during, and following recovery from the anesthetic state induced by thiopental in intact, chronically instrumented animal preparations. Results Intravenous administration of 15 mg/kg, but not 5 mg/kg, of thiopental to awake cats induced general anesthesia that was characterized by 5-10 min of cortical synchronization, reflected as large-amplitude slow-wave events and neck muscle atonia. However, even though the animal behaviorally began to reemerge from the anesthetic state after this 5-10-min period, neck muscle (neck motoneuron) activity recovered more slowly and remained significantly suppressed for up to 23 min after thiopental administration. The spontaneous activity of both dorsal spinocerebellar and spinoreticular tract neurons was maximally suppressed 5 min after administration but remained significantly attenuated for up to 17 min after injection. Peripheral nerve and glutamate-evoked responses of dorsal spinocerebellar and spinoreticular tract neurons were particularly sensitive to thiopental administration and remained suppressed for up to 20 min after injection. Conclusions These results demonstrate that thiopental administration is associated with a prolonged blockade of motoneuron output and sensory transmission through the dorsal spinocerebellar and spinoreticular tracts that exceeds the duration of general anesthesia. Further, the blockade of glutamate-evoked neuronal responses indicates that these effects are due, in part, to a local action of the drug in the spinal cord. The authors suggest that this combination of lumbar sensory and motoneuron inhibition underlies the prolonged impairment of reflex coordination observed when thiopental is used clinically.

Ventral spinocerebellar tract neurons located in laminae V–VII of cat lumbar spinal cord were tested for the effects of ionophoretically applied monoamines and receptor selective agonists. Extracellularly recorded responses, monosynaptically evoked by group I afferents in a muscle nerve, were compared before, during, and after ionophoresis. They were analyzed with respect to changes in the number of evoked spikes and in the latency. Both serotonin (5-HT) and noradrenaline (NA) were found to facilitate responses of all neurons tested. Ionophoresis of three serotonin subtype receptor agonists (5-carboxamidotryptamine maleate, 5 methoxytryptamine HCl, and alpha-methyl 5-hydroxytryptamine) and of two NA receptor agonists (phenylephrine and isoproterenol) likewise had a facilitatory effect. However, three other 5-HT receptor agonists (8-hydroxy-dipropylaminotetraline hydrobromide), 2-methyl 5-hydroxytryptamine, and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl and two NA receptor agonists (tizanidine and clonidine) had the opposite effect because they depressed responses of the tested neurons. These results show that information forwarded by means of the ventral spinocerebellar tract may be modulated by monoamines and that several receptor subtypes, located pre- or postsynaptically, may be involved. The results also demonstrate that transmission by means of group I muscle afferents may not only be facilitated by monoamines but also depressed by selective receptor subtype activation. J. Comp. Neurol. 443:298–309, 2002. © 2002 Wiley-Liss, Inc.

We aimed to explore the cerebellar cortical inputs from two spinocerebellar pathways, the spinal border cell-component of the ventral spinocerebellar tract (SBC-VSCT) and the dorsal spinocerebellar tract (DSCT), respectively, in the sublobule C1 of the cerebellar posterior lobe. The two pathways were activated by electrical stimulation of the contralateral lateral funiculus (coLF) and the ipsilateral LF (iLF) at lower thoracic levels. Most granule cells in sublobule C1 did not respond at all but part of the granule cell population displayed high-intensity responses to either coLF or iLF stimulation. As a rule, Golgi cells and Purkinje cell simple spikes responded to input from both LFs, although Golgi cells could be more selective. In addition, a small population of granule cells responded to input from both the coLF and the iLF. However, in these cases, similarities in the temporal topography and magnitude of the responses suggested that the same axons were stimulated from the two LFs, i.e., that the axons of individual spinocerebellar neurons could be present in both funiculi. This was also confirmed for a population of spinal neurons located within known locations of SBC-VSCT neurons and dorsal horn (dh) DSCT neurons. We conclude that bilateral spinocerebellar responses can occur in cerebellar granule cells, but the VSCT and DSCT systems that provide the input can also be organized bilaterally. The implications for the traditional functional separation of VSCT and DSCT systems and the issue whether granule cells primarily integrate functionally similar information or not are discussed.

Proprioception is the ability to interpret our musculo-skeletal state (e.g., position and movement) by processing information originating from our own body. While it is generally accepted that passive proprioception (i.e., proprioception in the absence of muscle contraction) is dependent only on the processing of peripheral inputs, the precise nature of the processes constituting active proprioception (i.e., proprioception with muscle contraction) is still not clear (Proske and Gandevia, 2012). Central to this knowledge gap is the difficulty in accurately determining the processes responsible for the improvement of proprioception in active compared to passive movements (e.g., Fuentes and Bastian, 2010). This improvement is assumed to potentially result from [1] enhanced peripheral muscle information (through gamma motoneurons of the muscle spindles), [2] the direct transmission of a copy of motor commands (i.e., efference copy) from motor to sensory processing areas, and/or [3] the involvement of predictive models through the cerebellum (Wolpert and Miall, 1996; Bhanpuri et al., 2012; Proske and Gandevia, 2012). Here, based on the results of Bhanpuri et al. (2013), we propose that cerebellar predictive models can fully account for the improvement of proprioception in active movements. We also describe the cellular arrangement that may underlie the involvement of predictive models in proprioception. In their recent study, Bhanpuri et al. (2013) tested proprioception in cerebellar patients and well matched controls. They measured perceptual thresholds of the dominant arm using an exoskeleton robot system in three proprioceptive tasks: passive, active (active-simple), and active with a complex pattern of resistive torque during forearm displacement making this displacement unpredictable (active-complex). Based on Weber fractions, controls demonstrated better proprioception in the active-simple task compared to the passive (p 0.38). In contrast, no differences were found between any of the tasks in cerebellar patients (all p > 0.28), who performed worse than controls in the active-simple task (p < 0.03). The similar performance observed in the passive and active-complex task in controls reveals that the proprioceptive benefit usually observed in active compared to passive conditions is neither related to an enhancement of information from the peripheral muscle [1] nor to the direct transmission of an efference copy from motor to sensory areas [2]. Indeed, these two processes may have been operating in the active-complex task but did not improve proprioceptive performance compared to the passive task. Furthermore, the absence of improvement in the active-simple task compared to the passive task in cerebellar patients demonstrates that the improved proprioception observed in the active-simple task in controls can be fully accounted for by a process located in the cerebro-cerebellar loop. Finally, cerebellar patients demonstrated a lower performance level than controls in the active-simple (predictable) task but not in the active-complex (non-predictable) task. Therefore the process that is most likely responsible for the improvement in proprioception is predictive modeling, which is thought to be supported by the cerebellum [3]. A recent study in mice demonstrates that individual granule cells in the cerebellum can mix proprioceptive afferents from the spinocerebellar tract and efference copy from the cerebral cortex (Huang et al., 2013). This multimodal arrangement provides the anatomical basis for converting motor corollary discharges into sensory coordinates. Indeed, granule cells can generate action potentials in response to a single input (Rancz et al., 2007). Therefore, sensory and motor-related inputs can potentially substitute for one another to fire a granule cell. The nature of the granule cells' output is still unknown. However, studies testing experimental phantom limbs by blocking peripheral nerves revealed conscious sensations of limb movement in the absence of any sensory input when subjects attempted to move (e.g., Gandevia et al., 2006). This result clearly supports a conversion of the efference copy from motor to sensory coordinates making proprioceptive prediction possible. So far, the literature has emphasized the role of predictive models in the control of movement where intended actions are compared with actual actions to generate error signals. However, results from Bhanpuri et al. (2013) as well as studies of phantom limbs demonstrate that the purpose of cerebellar processes is not only motor control but also proprioception per se.

WGA-Alexa 488 is a fluorescent neuronal tracer that demonstrates transsynaptic transport in the central nervous system. The transsynaptic transport occurs over physiologically active synaptic connections rather than less active or silent connections. Immediately following C2 spinal cord hemisection (C2Hx), when WGA-Alexa 488 is injected into the ipsilateral hemidiaphragm, the tracer diffuses across the midline of the diaphragm and retrogradely labels the phrenic nuclei (PN) bilaterally in the spinal cord. Subsequently, the tracer is transsynaptically transported bilaterally to the rostral Ventral Respiratory Groups (rVRGs) in the medulla over physiologically active connections. No other neurons are labeled in the acute C2Hx model at the level of the phrenic nuclei or in the medulla. However, with a recovery period of at least 7weeks (chronic C2Hx), the pattern of WGA-Alexa 488 labeling is notably changed. In addition to the bilateral PN and rVRG labeling, the chronic C2Hx model reveals fluorescence in the ipsilateral ventral and dorsal spinocerebellar tracts, and the ipsilateral reticulospinal tract. Furthermore, interneurons are labeled bilaterally in laminae VII and VIII of the spinal cord as well as neurons in the motor nuclei bilaterally of the intercostal and forelimb muscles. Moreover, in the chronic C2Hx model, there is bilateral labeling of additional medullary centers including raphe, hypoglossal, spinal trigeminal, parvicellular reticular, gigantocellular reticular, and intermediate reticular nuclei. The selective WGA-Alexa 488 labeling of additional locations in the chronic C2Hx model is presumably due to a hyperactive state of the synaptic pathways and nuclei previously shown to connect with the respiratory centers in a non-injured model. The present study suggests that hyperactivity not only occurs in neuronal centers and pathways caudal to spinal cord injury, but in supraspinal centers as well. The significance of such injury-induced plasticity is that hyperactivity may be a mechanism to re-establish lost function by compensatory routes which were initially physiologically inactive.

The spinocerebellar systems are essential for the brain in the performance of coordinated movements, but our knowledge about the spinocerebellar interactions is very limited. Recently, several crucial pieces of information have been acquired for the spinal border cell (SBC) component of the ventral spinocerebellar tract (VSCT), as well as the effects of SBC mossy fiber activation in granule cells of the cerebellar cortex. SBCs receive monosynaptic input from the reticulospinal tract (RST), which is an important driving system under locomotion, and disynaptic inhibition from Ib muscle afferents. The patterns of activity of RST neurons and Ib afferents under locomotion are known. The activity of VSCT neurons under fictive locomotion, i.e. without sensory feedback, is also known, but there is little information on how these neurons behave under actual locomotion and for cerebellar granule cells receiving SBC input this is completely unknown. But the available information makes it possible to simulate the interactions between the spinal and cerebellar neuronal circuitries with a relatively large set of biological constraints. Using a model of the various neuronal elements and the network they compose, we simulated the modulation of the SBCs and their target granule cells under locomotion and hence generated testable predictions of their general pattern of modulation under this condition. This particular system offers a unique opportunity to simulate these interactions with a limited number of assumptions, which helps making the model biologically plausible. Similar principles of information processing may be expected to apply to all spinocerebellar systems.

This entry describes the gross anatomy of the spinal cord, including its blood supply, and its internal structure. The various descending motor pathways (corticospinal, rubrospinal, tectospinal, vestibulospinal and reticulospinal) and the ascending somatosensory pathways (anterolateral system (ALS), dorsal column–medial lemniscal system, and spinocerebellar) are described. The relationship of the gray matter and the white matter is discussed. The organization and connectivity of the gray matter in the ten Rexed's laminae are described in detail. Somatotopy in three important tracts – the lateral corticospinal, the dorsal columns, and the ALS – is emphasized.

An autopsied case of autosomal recessive hereditary spastic paraplegia with severe neurogenic muscular atrophy is described herein. This patient, a 16-year-old woman, presented with gait disturbance. She developed progressive spastic paralysis of the upper and lower limbs and mental deterioration. She became bedridden at approximately 40years of age. Dysarthria worsened at 45 years of age. She died of pneumonia at 50 years of age. Her younger sister has shown similar clinical symptoms and became bedridden at 37 years of age. Their parents were second cousins. Autopsy revealed a severely atrophic brain, weighing 720 g. The cerebral cortex was thin, and the white matter was extremely reduced in volume. Microscopically, neuronal loss and variable astrogliosis with diffuse spongy changes were evident at the cerebral cortex, thalamic nuclei, basal ganglia and hippocampus. The remaining neurons were atrophied with heavy deposition of lipofuscin. In the spinal cord, the pyramidal tracts as well as the dorsal spinocerebellar tracts were degenerated. In addition, marked loss of the anterior horn cells was seen. Severe neuronal loss of the nucleus gracilis was also detected. In contrast, only mild degeneration of the ventral spinocerebellar tracts and fasciulus cuneatus in the spinal cord were observed. In the frozen sections of skeletal muscle, severe neurogenic atrophy and fatty infiltration were evident. In addition, several rimmed vacuoles were observed in the atrophic fibers, and cytochrome coxidase-deficient fibers were present in part. Reduced nicotinamide adenine dinucleotide (NADH)-tetrazolium reductase reaction revealed abnormal accumulation of mitochondria around the center of the non-atrophic muscle fibers. It is suggested that an analysis of mitochondrial function of Japanese autosomal recessive hereditary spastic hemiplegia may provide additional information to clarify the pathogenesis.

In the upper cervical spinal segments, neurons in the medial part of lamina VI give rise to uncrossed spinocerebellar axons, whereas the central cervical nucleus (CCN) and neurons in laminae VII and VIII give rise to crossed spinocerebellar axons. Using anterograde labeling with biotinylated dextran in the rat, we examined the projections of these neuronal groups to the cerebellar nuclei. Uncrossed and crossed projections were distinguished by cerebellar lesions placed on the side contralateral or ipsilateral to the tracer injections confined to the second and third cervical spinal segments (C2 and C3, respectively). Labeled terminals of uncrossed projections were seen in the middle, dorsal, and ventrolateral parts of the middle subdivision and in the ventral part of the caudomedial subdivision of the medial nucleus. In the anterior interpositus nucleus, terminals were seen in the middle of the mediolateral extent, whereas, in the posterior interpositus nucleus, they were seen in lateral and caudal parts. The terminals of crossed projections from the CCN were distributed ventrally in medial to ventrolateral parts of the middle subdivision of the medial nucleus. Some terminals were seen in the caudomedial subdivision of the medial nucleus. In the anterior interpositus nucleus, labeled terminals were seen mainly in rostromedial parts, whereas, in the posterior interpositus nucleus, they were seen in caudal and dorsal parts of the medial half. The present study suggests that the medial lamina VI group and the CCN in the upper cervical segments project to the different areas of the cerebellar nuclei and are concerned with different functions. J. Comp. Neurol. 432:101–118, 2001. © 2001 Wiley-Liss, Inc.

In an autopsy case of sporadic rapidly progressive lower motor neuron disease (MND), Gallyas-positive argyrophilic and ubiquitinated filamentous intracytoplasmic inclusions were found in the neurons. Clinically, 7 months prior to death, a 68-year-old woman experienced a history of rapidly progressive muscle weakness of all four extremities and bulbar sign, without sensory and autonomic disturbance. Two months later, she became unable to stand or walk. Four months after onset, she needed respiratory support, and subsequently died due to cardiorespiratory arrest. Neuropathological examinations revealed neuronal loss and associated gliosis in the lower motor neurons, except for ocular motor nuclei, Clark’s column, and accessory cuneate nucleus, and tract degeneration was observed in the middle root zone of the posterior column and spinocerebellar tract. No Bunina bodies or Lewy body-like hyaline inclusions were found in the anterior horns. Gallyas-positive argyrophilic filamentous inclusions were found in the lower motor neurons and in nerve cells of the Clark’s column, intermediate zone, posterior horn and accessory cuneate nucleus. These were positive with anti-ubiquitin antibody but negative with anti-tau (tau-2 and AT8) and neurofilament antibodies. Electron microscopic examinations disclosed randomly arranged tubular-like filamentous profiles, with a diameter of 12–14 nm, sometimes with amorphous granules in the perikaryon. This is the first report on the Gallyas-positive argyrophilic and ubiquitinated filamentous inclusions in neurons in MND.

The organization of spinocerebellar tract (SCT) neurons in the chicken was studied quantitatively using retrograde wheat germ agglutinin-horseradish peroxidase labelling. The chicken spinal cord was divided into five regions based on the distribution of SCT neurons: the cervical region (the spinal segments [SS], 1–12, which contained 32% of the total number of SCT neurons), the cervical enlargement (SS13–15, 13.4%), the thoracic region (SS16–20, 13%), the thoraco-lumbosacral region (SS21–26, 34.6%), and the posterior lumbosacral region (SS27–30, 7%). Clarke’s column was found in two regions, a cervical one (SS12–16) and a lumbar one (SS21–28). The spinal border cells were less numerous and also present in two parts, a cervical one (SS10–15) and a caudal one (SS20–24). SCT neurons of the ventral part of the ventral horn were found in the cervical enlargement and SS16 (lamina VIII), and in the thoraco- and posterior lumbosacral regions (laminae VIII and IX). The ventral marginal nucleus consisted exclusively of SCT neurons but the major and minor marginal nuclei did not contain SCT neurons. In the cervical region most of SCT neurons were observed in the ventral horn, while the central cervical nucleus, which consists of SCT neurons in mammals, was not identified in the chicken.

The spinocerebellar tracts arising from the upper lumbar cord consist of the dorsal and the ventral spinocerebellar tracts (DSCT and VSCT), which ascend ipsilaterally and contralaterally, respectively. By using anterograde labeling with biotinylated dextran in the rat, this study examined whether the lumbar DSCT and the VSCT project to the cerebellar nuclei. Injections of the tracer were made unilaterally at levels between the L1 and L3 segments, with diffusion to either a rostral or a caudal segment. The injections resulted in bilateral labeling of axon terminals in the cerebellar nuclei. In the medial nucleus, labeled terminals were distributed in medial, ventral, and ventrolateral parts of the middle subdivision and ventral parts of the caudomedial subdivision. In the anterior interpositus nucleus, they were distributed in medial and dorsomedial parts throughout the rostrocaudal extent. Labeled terminals were seen within the dorsomedial crest region. In the posterior interpositus nucleus, labeled terminals were seen in the rostromedial extension, the caudomedial part, and the caudal pole. Labeled terminals were seen in the hilus and the ventral part of the lateral nucleus. Projections of the DSCT and the VSCT to these regions were confirmed after tracer injections preceded by sectioning of either tract. Both tracts projected bilaterally, but the DSCT projected mainly ipsilaterally. The present study suggests that the spinocerebellar tracts originating from the upper lumbar cord (the lumbar DSCT and the VSCT) project to specific areas of the cerebellar nuclei to transmit information about the peripheral and central events during the movement of hindlimbs. J. Comp. Neurol. 412:633–648, 1999. © 1999 Wiley-Liss, Inc.

Subacute combined degeneration is a rare cause of demyelination of the dorsal and lateral columns of the spinal cord and even more rarely of the pyramidal and spinocerebellar tracts and cerebellum. We present the initial and follow-up MRI appearances in a patient with subacute combined degeneration of the spinal cord, brain stem and cerebellum, due to vitamin B12 deficiency. The lesions in these structures were demonstrated clearly as pathologically high-signal areas on T2-weighted images. These lesions, except those of the brain stem and cerebellum, disappeared 4 months after therapy. MRI 14 months after the patient's discharge on vitamin B12 therapy showed the same picture.

We report clinicopathological features of a Japanese family with hereditary motor and sensory neuropathy associated with cerebellar atrophy (HMSNCA). Four affected members from a single generation were examined. They shared common clinical features, including insidious onset in teenage, slowly progressive cerebellar ataxia, amyotrophy, sensory disturbance, and dementia. In addition, all the patients showed hypoalbuminemia and hyperlipidemia and a marked atrophy of the cerebellum on magnetic resonance images. Autopsy of the proband revealed a severe loss of Purkinje cells, degeneration of posterior columns and spinocerebellar tracts of the spinal cord, and a marked loss of myelinated and unmyelinated fibers in the peripheral nerves. We consider that HMSNCA is a distinct form of hereditary multisystem neuronal degeneration.

We report on a case of sporadic amyotrophic lateral sclerosis (ALS) with prolonged, respirator-assisted survival and clinical signs limited to the upper and lower motor neuron systems. Autopsy revealed degeneration of the upper and lower neuron systems and Bunina bodies, both characteristic of ALS. In addition, we found degeneration of the spinocerebellar tracts, the substantia nigra and the dentatorubral system. Our case is an additional example of multisystem degeneration in ALS associated with prolonged, respirator-assisted survival. These findings suggest that sporadic ALS comprises heterogeneous subgroups with patterns of degeneration that depend, in part, on survival time.

The development and anatomy of the spinal cord are described. From the end of the third gestational week, the spinal cord sustains three developmental stages: neurulation, caudal differentiation and retrogressive differentiation. The anatomy of the spinal cord is discussed from the perspective of macroscopic findings, classification, level diagnosis, cytoarchitecture and white matter structures; especially variations of the pyramidal tract, and errors in textbook descriptions of the spinocerebellar tract.

We report three cases showing body lateropulsion as the sole or predominant symptom of caudal lateral medullary infarction. All of them presented a small infarction on the lateral surface of the caudal medulla corresponding to the dorsal spinocerebellar tract (DSCT). Disturbed unconscious proprioception of the lower trunk and the lower limb conveyed by the DSCT might have been responsible for the isolated lateropulsion. Although lateropulsion itself improved within two weeks, one patient's condition progressed to typical lateral medullary infarction. Lateropulsion caused by DSCT infarction could be a prodromal symptom of perfusion failure of a vertebral artery or the posterior inferior cerebellar artery.

Spinocerebellar systems are likely to be crucial for cerebellar hallmark functions such as coordination. However, in terms of cerebellar functional analyses, these are perhaps among the least explored systems. The aim of the present study is to achieve activation of a single component of the spinocerebellar systems and to explore to what extent it can influence the spike output of granule cells, Golgi cells, molecular layer interneurons (stellate and basket cells) and Purkinje cells. For this purpose, we took advantage of a unique arrangement discovered in neuroanatomical studies, in which the spinal border cell component of the ventral spinocerebellar system was found to be the only the only spinocerebellar tract which ascends in the contralateral lateral funiculus and have terminations in sublobulus C1 of the paramedian lobule in the posterior cerebellum. Using electrical stimulation of this tract, we find a subset of the cerebellar cortical neurons in this region to be moderately or powerfully activated. For example, some of our granule cells displayed high intensity responses whereas the majority of the granule cells displayed no response at all. The finding that more than half of the Purkinje cells were activated by stimulation of the spinal border cell tract indicated that this system is capable of directly influencing cerebellar cortical output. The implications of these findings for the view of the integrative functions of the cerebellar cortex are discussed.

A 65-year-old man with familial amyotrophic lateral sclerosis (ALS) with posterior column involvement showed fairly slow progression of the illness and lived with the aid of a respirator for 12 years. Neuropathological examinations showed simultaneous involvement of the pyramidal tract and lower motor neurons as well as degeneration in the Clarke’s nucleus- spinocerebellar tract- middle root zone of the posterior column, the pallido-luysian system, the medullary reticular formation, and widespread anterolateral columns of the spinal cord. However, the patient had no Lewy-body-like hyaline inclusions, which are characteristic features of this form of familial ALS. Moreover, no abnormalities were found in his SOD1 cDNA sequences. There seem to be certain heterogeneities in familial ALS with posterior column involvement, and SOD1 gene abnormalities may be involved in the pathomechanism in rapidly progressing ALS, in which there are Lewy-body-like hyaline inclusions.

Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited progressive neurological disorder characterized by neuronal degeneration and reactive gliosis in the cerebellum, brainstem, spinocerebellar tracts, and dorsal columns. Multiple system atrophy is a sporadic progressive neurological disorder with degeneration and gliosis in the basal ganglia, cerebellum, brainstem, and spinal autonomic nuclei, and with argyrophilic glial cytoplasmic inclusions. We describe 4 members of a family with the SCA1 mutation and a dominantly inherited progressive ataxia in which autopsy examination of 1 member showed neuropathological changes typical of multiple system atrophy, including glial cytoplasmic inclusions. In this patient, magnetic resonance imaging revealed marked brainstem and cerebellar volume loss and mild supratentorial generalized volume loss. Positron emission tomography with [18F]fluorodeoxyglucose revealed widespread hypometabolism in a pattern found in sporadic multiple system atrophy and not in dominantly inherited olivopontocerebellar atrophy. Positron emission tomography with [11C]flumazenil revealed normal benzodiazepine receptor distribution volumes, similar to those seen in sporadic multiple system atrophy. Two other family members still living had similar changes in the imaging studies. The findings in this family suggest that the SCA1 gene mutation can result in a disorder similar to multiple system atrophy, both clinically and neuropathologically.

Rationale: We examined injuries of the dentato-rubro-thalamic tract (DRTT), cortico-ponto-cerebellar tract (CPCT), dorsal spinocerebellar tract (SCT), and inferior cerebellar peduncle (ICP) in a patient with severe ataxia following bilateral tegmental pontine hemorrhage (PH), using diffusion tensor tractography (DTT). Patient concerns: A 75-year-old female patient underwent conservative management for bilateral tegmental PH. She presented with moderate motor weakness, severe resting and intentional tremor on both hands, and severe truncal ataxia (Scale for Assessment and Rating of Ataxia [25 points/0–40 points: a higher score indicates a worse state]), and she was not able to sit independently. Diagnoses and outcomes: On DTT taken at 2 weeks after initial presentation, both DRTTs and the left dorsal SCT were not reconstructed, whereas the CPCTs showed thinning of the entire pathways between the primary sensorimotor cortex and cerebellum in both hemispheres. The right ICP was discontinued at the transverse cerebellar branch of the ICP and thinning of the left ICP was observed in the vertical and transverse cerebellar branch of the ICP. Lessons: Using DTT, concurrent injuries of the DRTT, CPCT, dorsal SCT, and ICP were demonstrated in a patient with severe ataxia following PH. Our result suggests the necessity of evaluation of these neural tracts in patients who develop ataxia after brain injury.

The axons of spinal projection neurons transmit sensory information to the brain by ascending within highly organized longitudinal tracts. However, the molecular mechanisms that control the sorting of these axons within the spinal cord and their directed growth to poorly defined targets are not understood. Here, we show that an interplay between Robo and the cell adhesion molecule, N-cadherin, sorts spinal commissural axons into appropriate longitudinal tracts within the spinal cord, and thereby facilitates their brain targeting. Specifically, we show that d1 and d2 spinal commissural axons join the lateral funiculus within the spinal cord and target the cerebellum in chick embryos, and that these axons contribute to the spinocerebellar projection in transgenic reporter mice. Disabling Robo signaling or overexpressing N-cadherin on these axons prevents the formation of the lateral funiculus and the spinocerebellar tract, and simultaneously perturbing Robo and N-cadherin function rescues both phenotypes in chick embryos. Consistent with these observations, disabling Robo function in conditional N-cadherin knock-out mice results in a wild-type-like lateral funiculus. Together, these findings suggest that spinal projection axons must be sorted into distinct longitudinal tracts within the spinal cord proper to project to their brain targets.

Neurons of the dorsal spinocerebellar tracts (DSCT) have been described to be rhythmically active during walking on a treadmill in decerebrate cats, but this activity ceased following deafferentation of the hindlimb. This observation supported the hypothesis that DSCT neurons primarily relay the activity of hindlimb afferents during locomotion, but lack input from the spinal central pattern generator. The ventral spinocerebellar tract (VSCT) neurons, on the other hand, were found to be active during actual locomotion (on a treadmill) even after deafferentation, as well as during fictive locomotion (without phasic afferent feedback). In this study, we compared the activity of DSCT and VSCT neurons during fictive rhythmic motor behaviors. We used decerebrate cat preparations in which fictive motor tasks can be evoked while the animal is paralyzed and there is no rhythmic sensory input from hindlimb nerves. Spinocerebellar tract cells with cell bodies located in the lumbar segments were identified by electrophysiological techniques and examined by extra- and intracellular microelectrode recordings. During fictive locomotion, 57/81 DSCT and 30/30 VSCT neurons showed phasic, cycle-related activity. During fictive scratch, 19/29 DSCT neurons showed activity related to the scratch cycle. We provide evidence for the first time that locomotor and scratch drive potentials are present not only in VSCT, but also in the majority of DSCT neurons. These results demonstrate that both spinocerebellar tracts receive input from the central pattern generator circuitry, often sufficient to elicit firing in the absence of sensory input.

Nikolaus Friedreich (1825-1882) presented clinical findings in six patients with a severe hereditary disorder of the nervous system and secured full autopsies in four of them. He was fascinated by the spinal cord lesions in the siblings of two unrelated families, and in the first three of his five long articles stressed the destruction of the dorsal columns. He recognized the relatively minor symmetrical lesions of the anterolateral fasciculi but did not separate dorsal spinocerebellar tracts (Flechsig's bundles) and corticospinal tracts. Although he studied the dorsal spinal roots in great detail and established their principal abnormality, namely, axonal thinning without axonal loss, he reported dorsal root ganglia as entirely normal. He made an insightful description of atrophic neurons in the gracile nuclei (clavae) but overlooked the invariable atrophy of the dentate nuclei. He followed the families over a period of 14 years, but acknowledged the hereditary nature of the disease only very late. He proposed a developmental defect for the medulla oblongata, retaining his interpretation that the spinal lesion was inflammatory. This review honors Friedreich for his insight into a 'new' disease in the late 19th century and updates his neuropathological findings. It is remarkable that Friedreich also described the abnormal hearts in the disease that now bears his name since hypertrophic cardiomyopathy is now recognized as the main cause of death in Friedreich's ataxia.

Spinocerebellar ataxia type 7 is a neurodegenerative polyglutamine disease characterized by ataxia and retinal degeneration. The longitudinal course is unknown, and relationships between repeat expansion, clinical manifestations, and neuropathology remain uncertain. We followed 16 affected individuals of a 61-member kindred over 27 years with electroretinograms, neurological examinations including the Brief Ataxia Rating Scale, neuroimaging in five, and autopsy in four cases. We identified four stages of the illness: Stage 0, gene-positive but phenotypically silent; Stage 1, no symptoms, but hyperreflexia and/or abnormal electroretinograms; Stage 2, symptoms and signs progress modestly; and Stage 3, rapid clinical progression. CAG repeat length correlated inversely with age of onset of visual or motor signs (r = −0.74, p = 0.002). Stage 3 rate of progression did not differ between cases (p = 0.18). Electroretinograms correlated with Brief Ataxia Rating Scale score and were a biomarker of disease onset and progression. All symptomatic patients developed gait ataxia, extremity dysmetria, dysarthria, dysrhythmia, and oculomotor abnormalities. Funduscopy revealed pale optic discs and pigmentary disturbances. Visual acuity declined to blindness in those with longer CAG expansions. Hyperreflexia was present from Stage 1 onwards. Restless legs syndrome and sensory impairment were common. Neuropathological hallmarks were neuronal loss in cerebellar cortex, deep cerebellar nuclei, inferior olive, and anterior horns of the spinal cord, and axonal loss in spinocerebellar tracts, dorsal nerve roots, and posterior columns. Retinal pathology included photoreceptor degeneration and disruption of retinal pigment epithelium. Spinocerebellar ataxia type 7 evolves through four clinical stages; neuropathological findings underlie the clinical presentation; electroretinograms are a potential biomarker of disease progression.

AimLeukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is known as a relatively mild leukoencephalopathy. We investigated the occurrence of severe variants of LBSL with extensive brain magnetic resonance imaging (MRI) abnormalities. MethodMRIs of approximately 3,000 patients with an unknown leukoencephalopathy were retrospectively reviewed for extensive signal abnormalities of the cerebral and cerebellar white matter, posterior limb of the internal capsule, cerebellar peduncles, pyramids, and medial lemniscus. Clinical data were retrospectively collected. ResultsEleven patients fulfilled the MRI criteria (six males); six had DARS2 mutations. Clinical and laboratory findings did not distinguish between patients with and without DARS2 mutations, but MRI did. Patients with DARS2 mutations more often had involvement of structures typically affected in LBSL, including decussatio of the medial lemniscus, anterior spinocerebellar tracts, and superior and inferior cerebellar peduncles. Also, involvement of the globus pallidus was associated with DARS2 mutations. Earliest disease onset was neonatal; earliest death at 20 months. InterpretationThis study confirms the occurrence of early infantile, severe LBSL, extending the known phenotypic range of LBSL. Abnormality of specific brainstem tracts and cerebellar peduncles are MRI findings that point to the correct diagnosis. Copyright © 2012 by Thieme Medical Publishers, Inc.

Hereditary spastic paraparesis (HSP) is a neurodegenerative disorder, of which progressive spastic paraparesis is the clinical hallmark. Given the neuropathological evidence of degeneration of pyramidal tracts, dorsal columns, and dorsal spinocerebellar tracts, it is surprising that sensory symptoms are so indistinct compared to motor symptoms. We investigated the involvement of peripheral conduction and spinal proprioceptive pathways by nerve conduction studies, somatosensory evoked potentials of the median and tibial nerves, and quantitative assessment of the vibration perception thresholds of the hands and feet respectively in 32 patients suffering from HSP and healthy control groups. We did not find peripheral conduction abnormalities in HSP patients. Log-transformed vibration perception thresholds of the feet were abnormal in 13/32 HSP patients and in 0/64 controls (p < 0.00001), while tibial nerve somatosensory evoked potentials were abnormal in 20/32 patients and in 1/17 controls (p = 0.00001). The values for the upper extremities were within normal limits for nearly all subjects. In the HSP group, the neurophysiological disturbances did not correlate significantly with duration or severity of the disease, when age was controlled for, except for median nerve SSEP latency, which was affected by severity (p = 0.0072). We conclude that neurophysiological methods detected proprioceptive, subclinical abnormalities in several HSP patients, which may reflect degeneration of the dorsal columns, and/or dorsal spinocerebellar tracts. Since we found no correlation with several disease variables, the fact that not all HSP patients displayed these abnormalities may be caused by anatomical variations in proprioceptive pathways, rather than by phenotypical heterogeneity.

This report concerns an autopsy case of a peculiar neurodegenerative disorder associated with abnormal copper metabolism. The patient was a 46-year-old woman, who presented with dementia and ataxia, and who died after a progressive clinical course of approximately 19 months. The patient had marked hypocupremia and hypoceruloplasminemia. The neuropathological examination revealed: (1) neuronal loss with remarkable rarefaction of the neuropil of the mammillary body; (2) severe thalamic degeneration; (3) degeneration and softening of the olivary nucleus, accompanied by remarkable capillary proliferation; (4) coarse spongy state or vacuolization of the cerebral white matter, and (5) degeneration of Clarke's column. The cerebral cortex, basal ganglia, and cerebellar cortex were preserved; brain deposition of iron and copper was not detected. The liver showed congestion, parenchymal atrophy and iron deposition, but neither copper deposition nor cirrhotic changes. Although the clinical features of patients with neurological disorders associated with abnormal copper metabolism, but distinct from both Wilson's disease and Menkes' kinky hair disease have been described, no autopsy case report has been published to date. It is of particular interest that the subnuclear distribution pattern of the thalamic lesion and the isolated degeneration of Clarke's column and the posterior spinocerebellar tract of the spinal cord of the present patient closely resembled the lesions in Menkes' kinky hair disease.

The fiber course of the spinocerebellar tracts in the ventral and lateral funiculi of the cat spinal cord were studied by a new approach, making cordotomies at different spinal levels or lesions of the restiform body followed by injections of HRP or WGA-HRP into the anterior cerebellar lobe. The retrogradely labeled axons showed characteristic distribution patterns related to the level and extent of the lesions. The results show the following. 1) The dorsal spinocerebellar tract (DSCT) originating ipsilaterally from the thoracic and upper lumbar segments ascends in the dorsolateral fasciculus. It undergoes a dorsal shift during its rostral course. The tract is topically arranged and passes through the restiform body. 2) The ventral spinocerebellar tract (VSCT) arising contralaterally from lower thoracic, lumbar, and more caudal segments passes via the ventral funiculus and ascends in the ventrolateral fasciculus. This tract is also topically arranged. It makes a lateral and then a dorsal shift during its ascending course. The main portion of the VSCT enters the cerebellum via the superior cerebellar peduncle. A minor portion originating from the sacrococcygeal region enters via the restiform body. 3) The spinocerebellar fibers originating ipsilaterally from the cervical enlargement ascend in the lateralmost part of the lateral funiculus in the area between the dorsolateral and ventrolateral fasciculi. These fibers form two groups, one passing through the restiform body, the other through the superior cerebellar peduncle. 4) The spinocerebellar fibers originating contralaterally from the central cervical nucleus pass through the ventral funiculus and ascend in the lateralmost part of the lateral funiculus, mainly in the ventrolateral fasciculus. Most of the fibers seem to pass through the superior cerebellar peduncle.

This report presents a case of infantile multiple system atrophy with probably autosomal recessive inheritance. The female patient developed generalized muscular hypotonia, myoclonias and tonic-clonic seizures at the age of 8 months, followed by gradual development of choreoathetotic hyperkinesia and increasing psychomotor retardation. Metabolic disease was ruled out and the child died of aspiration pneumonia at the age of 5 years. General autopsy was unremarkable, but neuropathological examination showed degeneration of cerebellum, inferior olives, medial thalamus, Clarke's nucleus, anterior horn cells, corticospinal, spinocerebellar tracts, and posterior columns. Immunohistochemically many neurons contained intranuclear and intracytoplasmic ubiquitin-positive inclusions, which did not contain neurofilament or tau epitopes and ultra-structurally consisted of granulofilamentous material. We tentatively classify this case as a form of infantile multiple system atrophy linked to neuronal intranuclear hyaline inclusion disease.

The differential roles of thoracic spinocerebellar tract (SCT) neurons with axons ascending in ipsi- (uncrossed) and contralaterally (crossed) spinal cord and their activities during respiratory movement were examined by extracellular recordings in the T 9 –T 12 spinal segments of the anaesthetized cat. A total of 36 uncrossed and 7 crossed SCT neurons showed rhythmic discharges in relation to either spontaneous or artificial respiration. Uncrossed neurons were located in and around Clarke's column and thus are cells of origin of the dorsal spinocerebellar tract (DSCT). Crossed neurons were located in laminae VII and VIII. Almost all DSCT neurons were modulated during artificial respiration. Nineteen DSCT neurons showed high-frequency discharges during chest expansion and 15 DSCT neurons showed high-frequency discharges during the chest retraction phase of artificial respiration. Their respiration-related activity maintained the same phase relation and firing patterns after vagotomy. The phase relationship of neural rhythmicity to chest movement during artificial respiration and spontaneous breathing was the same in 14 neurons examined. Artificially induced pneumothorax caused a marked decrease of respiration-related modulation, and severing of a single nerve to the appropriate muscle caused a marked decrease of modulation, suggesting that respiration-related rhythmic activity of DSCT neurons is induced by the extension of respiratory muscles in the chest wall during both spontaneous and artificial respiration. Crossed SCT neurons showed rhythmic activity in phase with the central respiratory rhythm as indexed by phrenic nerve activity. Two neurons received an excitatory influence and five an inhibitory influence in the inspiratory phase from the centre. Four neurons in the latter group also received excitatory inputs from the periphery during chest expansion. Since inspiration brings chest expansion during spontaneous breathing, the central and peripheral inputs seem antagonistic in function. These neurons seemed to signal a discrepancy between the chest wall movement and the central respiratory rhythm. Functional differences between uncrossed and crossed SCTs in the lower thoracic segments in regard to the central and peripheral inputs as observed here are similar to those observed in the lumbar SCTs during locomotion.

A chronic progressive neurodegeneration, called hereditary porcine neuronal system degeneration (HPNSD), was recognized in a swine herd in Devon, England. Adult pigs that were presumed carriers of the dominantly inherited trait for HPNSD were transferred from England, where a breeding colony was maintained for 9 years, to the Wyoming State Veterinary Laboratory (WSVL) for study. Two litters of affected piglets were born to 2 carrier sows at the WSVL. Clinical signs of muscular tremors, paresis, or ataxia developed at 12–59 days of age in 4 of 6 liveborn pigs. Three other pigs were stillborn. In the 4 affected livebom pigs, clinical signs progressed and included symmetrical (3 pigs) or asymmetrical (1 pig) posterior paresis, bilateral knuckling of metatarsal-phalangeal or carpal joints, poor exercise tolerance, and in 1 pig, marked hind limb hypermetria. A 34-kg gilt exhibiting clinical signs of muscular tremors and posterior paresis and clinical signs for 22 days was euthanized and examined postmortem at 83 days of age. Apart from decubitus ulcers, gross lesions were absent. Microscopically, perikaryal vacuolation and osmiophilic lipid droplets were observed in atrophic alpha motor neurons in the spinal cord. There was axonal (Wallerian) degeneration in sulcomarginal and dorsal spinocerebellar tracts. Axonal degeneration also involved ventral but not dorsal spinal nerve roots, and was present in eight peripheral nerves sampled for histopathology. Changes in skeletal muscles were consistent with denervation atrophy and were most pronounced in M. tibialis cranialis of the 6 muscles sampled. Immunohistochemical staining of spinal cord for phosphorylated and nonphosphorylated neurofilaments did not reveal abnormal patterns, unlike some well-characterized inherited motor neuron diseases in other species.

Spinal somatosensory evoked potentials (SEP) were recorded in 58 normal mice (C3H strain) divided into 4 groups according to age (3-, 6-, 9- and 12 weeks). Monopolar recordings of spinal SEP were made by subdermal needle electrodes from 3 vertebral levels, ‘low-lumbar’, ‘high-lumbar’ and ‘mid-thoracic’, by stimulating the tibial nerve bilaterally at the ankle. Three negative peaks, NI, NII and NIII, presumably due to conduction through muscle afferents, cutaneous afferents (in the dorsal root or dorsal white column) and spinocerebellar tract, respectively, were recorded at the high-lumbar level in the 12-week-old mouse. Besides the NI and NII peaks, a small ventral root potential was also occasionally recorded at the low-lumbar level. At the mid-thoracic level, only NI and NIII were recordable. At both the high-lumbar and mid-thoracic levels, the negative peaks were superimposed over long duration ‘summation potentials’ of opposite polarities. Well-defined standing potentials were also recorded at these two levels. The standing potentials could be the ‘entry point potential’ due to the entry of S1 root into the spinal cord at the T13 vertebral level. The summation potential presumably is due to a fixed generator located between the T7 and T12 vertebral levels resulting from intense synaptic activity at this level. In 3- and 6-week-old mice, the entry point potential was recorded in the low-lumbar SEP also, possibly due to less axial growth of the vertebral column at this stage of development. The summation potential and NIII peak were reduced in size in these young mice, possibly due to less developed collaterals and synaptic activity. The somatosensory conduction velocity, measured between the low-lumbar and mid-thoracic recording sites, showed a highly significant increase during the 3–6 and 6–9 week periods, suggesting that a significant amount of myelination occurs in proprioceptive fibres postnatally in mice.

Neural circuits are organized into functional topographic maps. In order to visualize complex circuit architecture we developed an approach to reliably label the global patterning of multiple topographic projections. The cerebellum is an ideal model to study the orderly arrangement of neural circuits. For example, the compartmental organization of spinocerebellar mossy fibers has proven to be an indispensable system for studying mossy fiber patterning. We recently showed that wheat germ agglutinin (WGA) conjugated to Alexa 555 and 488 can be used for tracing spinocerebellar mossy fiber projections in developing and adult mice (Reeber et al. 2011). We found three major properties that make the WGA-Alexa tracers desirable tools for labeling neural projections. First, Alexa fluorophores are intense and their brightness allows for wholemount imaging directly after tracing. Second, WGA-Alexa tracers label the entire trajectory of developing and adult neural projections. Third, WGA-Alexa tracers are rapidly transported in both retrograde and anterograde directions. Here, we describe in detail how to prepare the tracers and other required tools, how to perform the surgery for spinocerebellar tracing and how best to image traced projections in three dimensions. In summary, we provide a step-by-step tracing protocol that will be useful for deciphering the organization and connectivity of functional maps not only in the cerebellum but also in the cortex, brainstem, and spinal cord.

Object The authors assessed the role of 3D anisotropy contrast (3DAC) in evaluating specific ascending tract degeneration in patients with cervical spondylotic myelopathy (CSM). Methods The authors studied 10 patients (2 women, 8 men; mean age 59.8 ± 14.6 years) with CSM and spinal cord compression below the C2–3 disc level, as well as 10 healthy control individuals (3 women, 7 men; mean age 42.0 ± 24.1 years). Images of the cervical cord at the C2–3 level were obtained using a 3.0-T MR imaging system. Results Three-dimensional anisotropy contrast imaging clearly made possible tract-by-tract analysis of the fasciculus cuneatus, fasciculus gracilis, and spinocerebellar tract. Tract degeneration identified using 3DAC showed good correlation with a decline in fractional anisotropy. Degeneration of the fasciculus gracilis detected by “vector contrast” demonstrated a good correlation with Nurick grades. Conclusions The study unambiguously demonstrated that 3DAC imaging is capable of assessing ascending tract degeneration in patients with CSM. Degeneration of an individual tract can be easily identified as a vector contrast change on the 3DAC image, a reflection of quantitative changes in anisotropism, similar to fractional anisotropy. Excellent correlation between Nurick grades and fasciculus gracilis degeneration suggests potential application of 3DAC imaging for tract-by-tract clinical correlation.

As formas nervosas crônicas da doença de Chagas comprometem tanto o sistema nervoso central (SNC) como o periférico, apesar de não serem encontradas com a frequência assinalada por Chagas em suas observações iniciais. O atual relato refere-se a uma paciente chagásica crônica desde a infância que, progressivamente, desenvolveu comprometimento da motricidade voluntária, do tono muscular, da coordenação, dos nervos cranianos. Sofria ainda de uma cardiopatia e de uma colopatia chagásicas, vindo a falecer no pós-operatório de uma hemicolectomia. Foi necropsiada e o estudo histopatológico do SNC revelou desmielinização dos feixes espinocerebelares e dos cordões posteriores, grande redução do número de células de Purkinje, grande destruição neuronal da substância negra e do locus coeruleus, estado lacunar dos núcleos da base, infiltração tecidual por corpúsculos de Herring aberrantes, porencefalia e espessamento meníngeo. The chronic nervous forms of Chagas' disease involve both the central and peripheral nervous systems although they are not detected at the frequency indicated by Chagas in his initial observations. The present report concerns a patient with chronic Chagas' disease since childhood who progressively developed involvement of voluntary motility, muscle tone, coordination, and cranial nerves. The patient also had Chagas' heart and colon disease. The patient died after surgery for hemicolectomy and was autopsied. Histologic study of the central nervous system revealed demyelination of the spinocerebellar tracts and posterior columns, a great reduction in the Purkinje cells number, extensive cell loss of the substantia nigra and locus coeruleus, lacunar state in the basal nuclei, tissue infiltration by aberrant Herring bodies, porencephaly, and thickening of the meninges.

This report concerns the evaluation of the clinicopathological features of amyotrophic lateral sclerosis (ALS) in two male patients who survived ten years with the assistance of artificial respirators. The patients were 54 and 52 years old at disease onset and they were placed on respirators 32 and 27 months later, respectively. The patients did not show impairments in occulomotor, sensory and rectovesical functions nor develop bedsores, with the tetrad of ALS being negative. The main histopathological changes observed include neuron loss of the upper and lower motor systems and degeneration of the pyramidal tract. By contrast, other systems such as the posterior column, spinocerebellar tracts, Clarke's nucleus, oculomotor nucleus and Onuf's nucleus remained intact. These findings on our two patients suggests that there may be cases in which the selective features of ALS are maintained throughout prolonged respiratory management.