Long-term recovery from a minimally responsive state with recovery of an injured ascending reticular activating system: A case report.

ABSTRACT: We report on a patient with hypoxic-ischemic brain injury (HI-BI) who showed recovery from a minimally consciousness state over 6 years concurrent with recovery of an injured ascending reticular activating system (ARAS), which was demonstrated on diffusion tensor tractography (DTT).A 31-year-old female patient, who suffered from HI-BI, showed impaired consciousness with a minimally conscious state: intermittently obeying simple motor tasks, such as "please grasp my hand." Her consciousness showed recovery with the passage of time; rapid recovery was observed during the recent 2 years.In the upper ARAS, the neural connectivity to both the basal forebrain and prefrontal cortex had increased on 8-year DTT compared with 1.5-year DTT. In the lower dorsal and ventral ARAS, no significant change was observed between 1.5 and 8 years DTTs.Recovery of an injured ARAS was demonstrated in a patient who showed recovery from a minimally consciousness state over 6 years following HI-BI. Our results suggest the brain target areas for recovery of impaired awareness in patients with disorders of consciousness.

The Gigantocellular Reticular Nucleus Plays a Significant Role in Locomotor Recovery after Incomplete Spinal Cord Injury.

Traditionally, the brainstem has been seen as hardwired and poorly capable of plastic adaptations following spinal cord injury (SCI). Data acquired over the past decades, however, suggest differently: following SCI in various animal models (lamprey, chick, rodents, nonhuman primates), different forms of spontaneous anatomic plasticity of reticulospinal projections, many of them originating from the gigantocellular reticular nucleus (NRG), have been observed. In line with these anatomic observations, animals and humans with incomplete SCI often show various degrees of spontaneous motor recovery of hindlimb/leg function. Here, we investigated the functional relevance of two different modes of reticulospinal fiber growth after cervical hemisection, local rewiring of axotomized projections at the lesion site versus compensatory outgrowth of spared axons, using projection-specific, adeno-associated virus-mediated chemogenetic neuronal silencing. Detailed assessment of joint movements and limb kinetics during overground locomotion in female adult rats showed that locally rewired as well as compensatory NRG fibers were responsible for different aspects of recovered forelimb and hindlimb functions (i.e., stability, strength, coordination, speed, or timing). During walking and swimming, both locally rewired as well as compensatory NRG plasticity were crucial for recovered function, while the contribution of locally rewired NRG plasticity to wading performance was limited. Our data demonstrate comprehensively that locally rewired as well as compensatory plasticity of reticulospinal axons functionally contribute to the observed spontaneous improvement of stepping performance after incomplete SCI and are at least partially causative to the observed recovery of function, which can also be observed in human patients with spinal hemisection lesions.SIGNIFICANCE STATEMENT Following unilateral hemisection of the spinal cord, reticulospinal projections are destroyed on the injured side, resulting in impaired locomotion. Over time, a high degree of recovery can be observed in lesioned animals, like in human hemicord patients. In the rat, recovery is accompanied by pronounced spontaneous plasticity of axotomized and spared reticulospinal axons. We demonstrate the causative relevance of locally rewired as well as compensatory reticulospinal plasticity for the recovery of locomotor functions following spinal hemisection, using chemogenetic tools to selectively silence newly formed connections in behaviorally recovered animals. Moving from a correlative to a causative understanding of the role of neuroanatomical plasticity for functional recovery is fundamental for successful translation of treatment approaches from experimental studies to the clinics.

Distinct Corticospinal and Reticulospinal Contributions to Voluntary Control of Elbow Flexor and Extensor Muscles in Humans with Tetraplegia.

Humans with cervical spinal cord injury (SCI) often recover voluntary control of elbow flexors and, to a much lesser extent, elbow extensor muscles. The neural mechanisms underlying this asymmetrical recovery remain unknown. Anatomical and physiological evidence in animals and humans indicates that corticospinal and reticulospinal pathways differentially control elbow flexor and extensor motoneurons; therefore, it is possible that reorganization in these pathways contributes to the asymmetrical recovery of elbow muscles after SCI. To test this hypothesis, we examined motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation over the arm representation of the primary motor cortex, maximal voluntary contractions, the StartReact response (a shortening in reaction time evoked by a startling stimulus), and the effect of an acoustic startle cue on MEPs elicited by cervicomedullary stimulation (CMEPs) on biceps and triceps brachii in males and females with and without chronic cervical incomplete SCI. We found that SCI participants showed similar MEPs and maximal voluntary contractions in biceps but smaller responses in triceps compared with controls, suggesting reduced corticospinal inputs to elbow extensors. The StartReact and CMEP facilitation was larger in biceps but similar to controls in triceps, suggesting enhanced reticulospinal inputs to elbow flexors. These findings support the hypothesis that the recovery of biceps after cervical SCI results, at least in part, from increased reticulospinal inputs and that the lack of these extra inputs combined with the loss of corticospinal drive contribute to the pronounced weakness found in triceps.SIGNIFICANCE STATEMENT Although a number of individuals with cervical incomplete spinal cord injury show limited functional recovery of elbow extensors compared with elbow flexor muscles, to date, the neural mechanisms underlying this asymmetrical recovery remain unknown. Here, we provide for the first time evidence for increased reticulospinal inputs to biceps but not triceps brachii and loss of corticospinal drive to triceps brachii in humans with tetraplegia. We propose that this reorganization in descending control contributes to the asymmetrical recovery between elbow flexor and extensor muscles after cervical spinal cord injury.

Effects of injuries to descending motor pathways on restoration of gait in patients with pontine hemorrhage.

BACKGROUND AND PURPOSE: Gait disturbance due to injuries of the descending motor pathway, including corticospinal tract (CST), corticoreticular pathway (CRP), and medial and lateral vestibulospinal tracts (VSTs), are commonly encountered disabling sequelae of pontine hemorrhage. We investigated relations between changes in the CST, CRP, and medial and lateral VST and corresponding changes in gait function in patients with pontine hemorrhage. METHOD: Nine consecutive stroke patients with pontine hemorrhage, and 6 age-matched normal subjects were recruited. Four patients were allocated to group A (can't walk independently) and 5 to group B (can walk independently). Diffusion tensor imaging (DTI) data were acquired twice at acute to subacute stage and chronic stage after stroke onset. Diffusion tensor tractography (DTT) was used to reconstruct CST, CRP, medial and lateral VST. RESULT: The CRP shows a significantly different between groups A and B in both initial and follow up DTT (p > 0.05). In contrast, CST, medial VST and lateral VST did not show a significant difference (p > 0.05). Regarding DTI parameters of CRPs in group A, percentages of patients with fractional anisotropy (FA) and mean diffusivity (MD) values more than two standard deviation from normal were higher by follow up DTI than by initial DTI, however, the CRPs in group B only showed increased abnormal range of MD. CONCLUSIONS: The CST does not play an essential role in recovery of independent walking and vestibulospinal tracts may not crucially affect recovery of independent walking in patients with pontine hemorrhage. In contrast, and intact CRP or changes of the CRP integrity appear to be related to the recovery of gait function.

The Relationship Between Enhanced Reticulospinal Outflow and Upper Limb Function in Chronic Stroke Patients.

BACKGROUND: Recent evidence from both monkey and human studies suggests that the reticulospinal tract may contribute to recovery of arm and hand function after stroke. In this study, we evaluated a marker of reticulospinal output in stroke survivors with varying degrees of motor recovery. METHODS: We recruited 95 consecutive stroke patients presenting 6 months to 12 years after their index stroke, and 19 heathy control subjects. Subjects were asked to respond to a light flash with a rapid wrist flexion; at random, the flash was paired with either a quiet or loud (startling) sound. The mean difference in electromyogram response time after flash with quiet sound compared with flash with loud sound measured the StartReact effect. Upper limb function was assessed by the Action Research Arm Test (ARAT), spasticity was graded using the Modified Ashworth Scale (MAS) and active wrist angular movement using an electrogoniometer. RESULTS: StartReact was significantly larger in stroke patients than healthy participants (78.4 vs 45.0 ms, P < .005). StartReact showed a significant negative correlation with the ARAT score and degree of active wrist movement. The StartReact effect was significantly larger in patients with higher spasticity scores. CONCLUSION: We speculate that in some patients with severe damage to their corticospinal tract, recovery led to strengthening of reticulospinal connections and an enhanced StartReact effect, but this did not occur for patients with milder impairment who could use surviving corticospinal connections to mediate recovery.

Outgrowing seizures in Childhood Absence Epilepsy: time delays and bistability.

We formulate a conductance-based model for a 3-neuron motif associated with Childhood Absence Epilepsy (CAE). The motif consists of neurons from the thalamic relay (TC) and reticular nuclei (RT) and the cortex (CT). We focus on a genetic defect common to the mouse homolog of CAE which is associated with loss of GABAA receptors on the TC neuron, and the fact that myelination of axons as children age can increase the conduction velocity between neurons. We show the combination of low GABAA mediated inhibition of TC neurons and the long corticothalamic loop delay gives rise to a variety of complex dynamics in the motif, including bistability. This bistability disappears as the corticothalamic conduction delay shortens even though GABAA activity remains impaired. Thus the combination of deficient GABAA activity and changing axonal myelination in the corticothalamic loop may be sufficient to account for the clinical course of CAE.

Spike discharge characteristic of the caudal mesencephalic reticular formation and pedunculopontine nucleus in MPTP-induced primate model of Parkinson disease.

The pedunculopontine nucleus (PPN) included in the caudal mesencephalic reticular formation (cMRF) plays a key role in the control of locomotion and wake state. Regarding its involvement in the neurodegenerative process observed in Parkinson disease (PD), deep brain stimulation of the PPN was proposed to treat levodopa-resistant gait disorders. However, the precise role of the cMRF in the pathophysiology of PD, particularly in freezing of gait and other non-motor symptoms is still not clear. Here, using micro electrode recording (MER) in 2 primates, we show that dopamine depletion did not alter the mean firing rate of the overall cMRF neurons, particularly the putative non-cholinergic ones, but only a decreased activity of the regular neurons sub-group (though to be the cholinergic PPN neurons). Interestingly, a significant increase in the relative proportion of cMRF neurons with a burst pattern discharge was observed after MPTP intoxication. The present results question the hypothesis of an over-inhibition of the CMRF by the basal ganglia output structures in PD. The decreased activity observed in the regular neurons could explain some non-motor symptoms in PD regarding the strong involvement of the cholinergic neurons on the modulation of the thalamo-cortical system. The increased burst activity under dopamine depletion confirms that this specific spike discharge pattern activity also observed in other basal ganglia nuclei and in different pathologies could play a mojor role in the pathophysiology of the disease and could explain several symptoms of PD including the freezing of gait. The present data will have to be replicated in a larger number of animals and will have to investigate more in details how the modification of the spike discharge of the cMRF neurons in the parkinsonian state could alter functions such as locomotion and attentional state. This will ultimely allow a better comprehension of the pathophysiology of freezing of gait.

Restoration of the corticoreticular pathway following shunt operation for hydrocephalus in a stroke patient.

RATIONALE: We report on a stroke patient who showed restoration of discontinued corticoreticular pathways (CRPs) on serial diffusion tensor tractography (DTT) concurrent with recovery of gait disturbance following shunt operation for hydrocephalus. PATIENT CONCERNS: A 67-year-old female patient underwent stereotactic drainage for management of intraventricular hemorrhage due to a rupture of the left posterior communicating artery. DIAGNOSES: After 4 weeks from onset, the patient exhibited quadriparesis with more severe weakness in the proximal muscles and could not even stand or walk. She underwent comprehensive rehabilitation for 3 weeks. Her quadriparesis, as a result of hydrocephalus, did not improve significantly. INTERVENTIONS: On the pre-op DTT, discontinuations (the right CRP: at subcortical white matter level, and the left CRP: at the midbrain level) of the CRP fibers from the premotor cortex were observed in both hemispheres. OUTCOMES: She underwent a ventriculo-peritoneal shunt operation and her quadriparesis improved, especially the proximal muscles. Consequently, she could walk with mild assistance on an even floor at 5 days and walk on stairs at 4 weeks after the shunt operation. On the post-op DTT, the discontinued CRP fibers were elongated to the premotor cortex in both hemispheres. LESSONS: Restoration of discontinued CRPs concurrent with recovery of gait disturbance following shunt operation for hydrocephalus was demonstrated in a stroke patient.

[Myoclonus as a movement disorder]. / Myoklonien als Bewegungsstörung.

Myoclonus is often a diagnostic and therapeutic challenge due to its broad phenomenological variability and limited therapeutic options. This article gives a short survey and characterizes in detail two common types of myoclonus, cortical myoclonus and reticular reflex myoclonus. Clinical testing and electrophysiological investigations provide relevant local diagnostic indications for the generating structure(s). Such indications would influence not only the strategies of neuroimaging and laboratory investigations aimed at clarifying the underlying cause but also the selection of drugs to suppress myoclonus.

CORRELATION INDICES OF CEREBRAL HEMODYNAMICS AND ELECTRICAL ACTIVITY IN CHILDREN WITH IMPAIRED MOTOR SKILLS.

The correlations between the indicators of cerebral hemodynamics and electrical activity in children with impaired motor skills of central origin (children with cerebral palsy) were investigated. There is established a high number of links between indicators of rheoencephalogram (REG) and electroencephalogram (EEG) in the left cerebral hemisphere than in the right. In frontomastoidal allocation 19 correlations and in occipitomastoidal - 59 links. We suppose that poor circulation in vertebroplasty-basilar system leads to the defeat of the brain stem, which, with afferent pathways of the reticular formation, connects the thalamus with the cortex. In the reticular formation there is an inhibition of ascending activators influences, which eland to decreasing of the cortex is tonus. You can talk about the functional immaturity of the system of nonspecific activation by the reticular formation of the brain stem. Children with violation of motor activity had significantly more negative and positive significant and high correlation among the existing indicators of electric brain activity and cerebral hemodynamics, in our opinion, is due to the development of interconnection compensation that is carried out by adjustment of the functional systems and the formation of new forms of adaptive responses in conditions of disontogenetik. Feature correlation pattern of the EEG, of children with disorders of motor activity, is associated with a significantly great number of high and significant correlations between measures of electrical brain activity in the δ- and q- rhythms, especially in the temporal areas of the cerebral cortex. According to visual analysis of EEG there is revealed a common manifestation of changes of bioelectric brain activity in children with disorders of motor activity. This is manifested in the development of paroxysmal activity of action potentials of θ- and δ-rhythms with the focus of activity in the anterior areas of the cerebral cortex; the formation of a mosaic representation of the θ-rhythms in temporal areas; the presence of hypersynchronous a-paroxysms in the posterior areas of the cerebral cortex. The given facts testify to activation of mechanisms of limbic-neocortical systems and synchronizing influences of the reticular formation of the stem and diencephalic structures. There is also detected greater number of correlations when occipitomastoidal registration was lone it reflects compensatory redistribution of cerebral blood flow over the affected structures of brain stem structures that are associated with the provision of cortical functions.

Evidence for a role of the reticulospinal system in recovery of skilled reaching after cortical stroke: initial results from a model of ischemic cortical injury.

The purposes of this pilot study were to create a model of focal cortical ischemia in Macaca fascicularis and to explore contributions of the reticulospinal system in recovery of reaching. Endothelin-1 was used to create a focal lesion in the shoulder/elbow representation of left primary motor cortex (M1) of two adult female macaques. Repetitive microstimulation was used to map upper limb motor outputs from right and left cortical motor areas and from the pontomedullary reticular formation (PMRF). In subject 1 with a small lesion and spontaneous recovery, reaching was mildly impaired. Changes were evident in the shoulder/elbow representations of both the lesioned and contralesional M1, and there appeared to be fewer than expected upper limb responses from the left (ipsilesional) PMRF. In subject 2 with a substantial lesion, reaching was severely impaired immediately after the lesion. After 12 weeks of intensive rehabilitative training, reach performance recovered to near-baseline levels, but movement times remained about 50% slower. Surprisingly, the shoulder/elbow representation in the lesioned M1 remained completely absent after recovery, and there was a little change in the contralesional M1. There was a definite difference in motor output patterns for left versus right PMRF for this subject, with an increase in right arm responses from right PMRF and a paucity of left arm responses from left PMRF. The results are consistent with increased reliance on PMRF motor outputs for recovery of voluntary upper limb motor control after significant cortical ischemic injury.

Tinnitus and hyperacusis involve hyperactivity and enhanced connectivity in auditory-limbic-arousal-cerebellar network.

Hearing loss often triggers an inescapable buzz (tinnitus) and causes everyday sounds to become intolerably loud (hyperacusis), but exactly where and how this occurs in the brain is unknown. To identify the neural substrate for these debilitating disorders, we induced both tinnitus and hyperacusis with an ototoxic drug (salicylate) and used behavioral, electrophysiological, and functional magnetic resonance imaging (fMRI) techniques to identify the tinnitus-hyperacusis network. Salicylate depressed the neural output of the cochlea, but vigorously amplified sound-evoked neural responses in the amygdala, medial geniculate, and auditory cortex. Resting-state fMRI revealed hyperactivity in an auditory network composed of inferior colliculus, medial geniculate, and auditory cortex with side branches to cerebellum, amygdala, and reticular formation. Functional connectivity revealed enhanced coupling within the auditory network and segments of the auditory network and cerebellum, reticular formation, amygdala, and hippocampus. A testable model accounting for distress, arousal, and gating of tinnitus and hyperacusis is proposed.

The spino-bulbar-cerebellar pathway: Activation of neurons projecting to the lateral reticular nucleus in the rat in response to noxious mechanical stimuli.

It is now well established that the cerebellum receives input from nociceptors which may serve to adjust motor programmes in response to pain and injury. In this study, we investigated the possibility that spinoreticular neurons (SRT) which project to a pre-cerebellar nucleus, the lateral reticular nucleus (LRt), respond to noxious mechanical stimulation. Seven adult male rats received stereotaxic injections of the b subunit of cholera toxin in the LRt. Following a 5 day interval, animals were anesthetised with urethane and a noxious mechanical stimulus was applied to the right hind paw. Animals were fixed by perfusion 5min following application of the stimulus. Retrogradely labelled SRT neurons of the lumbar spinal cord were examined for immunoreactivity for phosphorylated ERK (pERK) and the neurokinin-1 (NK-1) receptor. Approximately 15% of SRT cells in deep laminae (IV-VII and X) expressed pERK ipsilateral to the site of the stimulus. Around 60% of SRT cells with the NK-1 receptor expressed pERK but 5% of pERK expressing cells were negatively labelled for NK-1. It is concluded that a significant proportion of SRT cells projecting to the LRt respond to noxious mechanical stimuli and that one of the functions of this pathway may be to provide the cerebellum with nociceptive information.

The mesencephalic nucleus of the trigeminal nerve and the SIDS.

Sudden infant death syndrome (SIDS) is a major cause of infant mortality throughout the world, yet its cause and mechanism of action remain poorly understood. Here, we discuss a novel model of the etiology of SIDS which ties together what is known about the brain regions thought to be affected in SIDS infants with a defined neuroanatomical circuit and a documented preventative factor in young children. We propose that SIDS occurs due to a lack of sufficient development and plasticity of glutamatergic synapses in the mesencephalic nucleus of the trigeminal nerve (Me5) and reticular formation (RF) of the brainstem. This model is supported by evidence of brainstem dysfunction in SIDS as well as evidence of signaling through the Me5 and RF in another means of regulating cortical arousal. Furthermore, long-term plasticity of glutamatergic synapses is well known to play a critical role in learning and memory in other regions of the brain, implying that those mechanisms may also be relevant in the development of brainstem circuitry. This model clearly explains why SIDS deaths appear so suddenly with little pathological explanation and suggests a potentially novel way to prevent these deaths from occurring.

Intrinsic connections within the pedunculopontine tegmental nucleus are critical to the elaboration of post-ictal antinociception.

This study investigated the intrinsic connections of a key-structure of the endogenous pain inhibitory system, the pedunculopontine tegmental nucleus (PPTN), in post-ictal antinociceptive process through synaptic inactivation of the PPTN with cobalt chloride. Male Wistar rats (n = 6 or 7 per group), weighing 250-280 g, had the tail-flick baseline recorded and were submitted to a stereotaxic surgery for the introduction of a guide-cannula aiming at the PPTN. After 5 days of postoperative recovery, cobalt chloride (1 mM/0.2 µL) or physiological saline (0.2 µL) were microinjected into the PPTN and after 5 min, the tail-withdrawal latency was measured again at 0, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, and 120 min after seizures evoked by intraperitoneal injection of pentylenetetrazole (64 mg/kg). The synaptic inactivation of PPTN decreased the post-ictal antinociceptive phenomenon, suggesting the involvement of PPTN intrinsic connections in the modulation of pain, during tonic-clonic seizures. These results showed that the PPTN may be crucially involved in the neural network that organizes the post-ictal analgesia.

Behavioral anxiolysis without reduction of hippocampal theta frequency after histamine application in the lateral septum of rats.

Hippocampal theta activity is linked to various processes, including locomotion, learning and memory, and defense and affect (i.e., fear and anxiety). Interestingly, all classes of clinically effective anxiolytics, as well as experimental compounds that decrease anxiety in pre-clinical animal models of anxiety, reduce the frequency of hippocampal theta activity elicited by stimulation of the reticular formation in freely behaving or anesthetized animals. In the present experiments, we found that bilateral histamine infusions (0.5 µg/hemisphere) into the lateral septum (LS) of rats decreased anxiety-like responses in two models of anxiety, the elevated plus maze and novelty-induced suppression of feeding test. Surprisingly, these same infusions significantly increased hippocampal theta frequency elicited by reticular stimulation in urethane-anesthetized rats. In contrast to these findings, additional experiments showed that the clinically effective anxiolytic buspirone (40 mg/kg, i.p.) reduced theta frequency, confirming previous observations. Taken together, the dissociation of behavioral anxiolysis and theta frequency reduction noted here suggest that hippocampal theta frequency is not a direct index of anxiety levels in rodents. Further, the mechanisms underlying the behavioral and physiological effects elicited by histamine in the LS require further study.

Overactive bladder and pontine reticular formation.

BACKGROUND: The etiology of overactive bladder (OAB) remains unclear. Observed neurogenic factors in the literature are limited to suprapontine or spinal pathologies. The blink reflex is a useful tool in the evaluation of brainstem functions. Blink reflex latency times were evaluated in order to reveal pathology in the brainstem. METHODS: A total of 60 women, 30 patients with idiopathic OAB and 30 healthy controls, were enrolled in the study. Blink reflex latency times were analyzed by electrical stimulation of the supraorbital nerve. Two responses in the orbicularis oculi muscle, early ipsilateral response (R1) and late bilateral response (R2) latency times, were recorded. RESULTS: Mean ages of the patients and controls were 51.9 ± 5.3 and 49.2 ± 6.2 years, respectively. R2 latency times were significantly higher in patients than in controls. However, R1 latency times were similar between the two groups. CONCLUSIONS: The results of the study suggest a significant relation between late blink latency times and OAB. An oligosynaptic path via the trigeminal nuclei is responsible for R1; however, R2 response is relayed through the reticular formation. Stimulation of pontine reticular formation inhibits micturition contraction. In some patients, idiopathic OAB may result from reticular formation-originated pathology. Additional studies on other reticular formation-mediated reflexes are needed to reveal possible dysfunction of reticular formation.

Neuromodulation of vegetative state through spinal cord stimulation: where are we now and where are we going?

BACKGROUND: Vegetative state (VS) is a complex condition that represents a challenging frontier for medicine and neuroscience research. Nowadays there is no scientifically validated treatment for VS patients, and their chronic long-term assistance is very demanding for healthcare systems worldwide. OBJECTIVES: The present paper is a systematic review of the role of spinal cord stimulation (SCS) as a treatment of patients with VS. METHODS: Published literature on this topic was analyzed systematically. Clinical and epidemiological characteristics of VS, present therapeutic options and social costs of VS were also evaluated. RESULTS: Only 10 papers have been published since 1988, and overall 308 VS patients have been treated with SCS worldwide; 51.6% displayed a clinical improvement and an amelioration of the environmental interaction. These effects are probably mediated by the stimulation of the reticular formation-thalamus-cortex pathway and by cerebral blood flow augmentation induced by SCS. CONCLUSIONS: The experience on this topic is still very limited, and on this basis it is still hard to make any rigorous assessment. However, the most recent experiments represent significant progress in the research on this topic and display SCS as a possible therapeutic tool in the treatment of VS.

Injury of the corticoreticular pathway in patients with proximal weakness following cerebral infarct: diffusion tensor tractography study.

The corticoreticular pathway (CRP) innervates mainly the proximal muscles of extremities. Identification of the CRP by diffusion tensor tractography (DTT) in the human brain has recently become possible. However, little is known about the relation between proximal weakness and injury of the CRP in stroke patients. In this study, we attempted to investigate the usefulness of DTT for elucidation of the relation between proximal motor weakness and injury of the CRP in patients with cerebral infarct. Among 247 consecutive patients with cerebral infarct, four hemiparetic patients who showed more severe weakness in proximal joints (shoulder and hip) than distal joints (finger and ankle) of the affected extremities were recruited for this study. Evaluation of motor function, DTT, and transcranial magnetic stimulation (TMS) for evaluation of the corticospinal tract state by analysis of the characteristics of the motor-evoked potential were performed at the early stage of cerebral infarct (mean: 17.0 days; range: 11-29). The integrity of the CST on DTT findings in the affected hemisphere was preserved in all four patients and TMS findings in terms of latency and amplitude showed within normal range (one patient) and partial injuries (three patients) of the corticospinal tract. By contrast, on DTT of the CRP in the affected hemispheres, we observed Wallerian degeneration in two patients and discontinuations at infarct level in two patients. The injury of the CRP appeared to attribute the proximal weakness of the shoulder and hip observed in these four patients. Therefore, DTT of the CRP would be useful for elucidating the relation between proximal weakness and injury of the CRP in patients with cerebral infarct.