Corticospinal Tract Impairment Research Articles

Generation and Characterization of hiPS Lines from Three Patients Affected by Different Forms of HPDL-Related Neurological Disorders.

Hereditary spastic paraplegias are rare genetic disorders characterized by corticospinal tract impairment. Spastic paraplegia 83 (SPG83) is associated with biallelic mutations in the HPDL gene, leading to varied severities from neonatal to juvenile onset. The function of HPDL is unclear, though it is speculated to play a role in alternative coenzyme Q10 biosynthesis. Here, we report the generation of hiPS lines from primary skin fibroblasts derived from three SPG83 patients with different HPDL mutations, using episomal reprogramming. The patients' clinical characteristics are carefully listed. The hiPS lines were meticulously characterized, demonstrating typical pluripotent characteristics through immunofluorescence assays for stemness markers (OCT4, TRA1-60, NANOG, and SSEA4) and RT-PCR for endogenous gene expression. Genetic integrity and identity were confirmed via Sanger sequencing and short tandem repeat analysis. These hiPS cells displayed typical pluripotent characteristics and were able to differentiate into neocortical neurons via a dual SMAD inhibition protocol. In addition, HPDL mutant neurons assessed via long-term culturing were able to achieve effective maturation, similarly to their wild-type counterparts. The HPDL hiPS lines we generated will provide a valuable model for studying SPG83, offering insights into its molecular mechanisms and potential for developing targeted therapies.

A comparative study of diffusion kurtosis imaging and diffusion tensor imaging in detecting corticospinal tract impairment in diffuse glioma patients.

This study aimed to investigate the diagnostic performance of diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) in identifying aberrations in the corticospinal tract (CST), whilst elucidating the relationship between abnormalities of CST and patients' motor function. Altogether 21 patients with WHO grade II or grade IV glioma were enrolled and divided into Group 1 and Group 2, according to the presence or absence of preoperative paralysis. DKI and DTI metrics were generated and projected onto the CST. Histograms of the CST along x, y, and z axes were developed based on DKI and DTI metrics, and compared subsequently to determine regions of aberrations on the fibers. The receiver operating characteristic curve was performed to investigate the diagnostic efficacy of DKI and DTI metrics. In Group 1, a significantly lower fractional anisotropy, radial kurtosis and mean kurtosis, and a higher mean diffusivity were found in the ipsilateral CST as compared to the contralateral CST. Significantly higher relative axial diffusivity, relative radial diffusivity, and relative mean diffusivity (rMD) were found in Group 1, as compared to Group 2. The relative volume of ipsilateral CST abnormalities higher than the maximum value of mean kurtosis combined with rMD exhibited the best diagnostic performance in distinguishing dysfunction of CST with an AUC of 0.93. DKI is sensitive in detecting subtle changes of CST distal from the tumor. The combination of DKI and DTI is feasible for evaluating the impairment of the CST.

Genetic origin of patients having spastic paraplegia with or without other neurologic manifestations

BackgroundHereditary spastic paraplegia (HSP) is a group of neurodegenerative diseases characterized by lower-limb spastic paraplegia with highly genetic and clinical heterogeneity. However, the clinical sign of spastic paraplegia can also be seen in a variety of hereditary neurologic diseases with bilateral corticospinal tract impairment. The purpose of this study is to identify the disease spectrum of spastic paraplegia, and to broaden the coverage of genetic testing and recognize clinical, laboratorial, electrophysiological and radiological characteristics to increase the positive rate of diagnosis.MethodsTwenty-seven cases were screened out to have definite or suspected pathogenic variants from clinically suspected HSP pedigrees through HSP-associated sequencing and/or expanded genetic testing. One case was performed for enzyme detection of leukodystrophy without next-generation sequencing. In addition, detailed clinical, laboratorial, electrophysiological and radiological characteristics of the 28 patients were presented.ResultsA total of five types of hereditary neurological disorders were identified in 28 patients, including HSP (15/28), leukodystrophy (5/28), hereditary ataxia (2/28), methylmalonic acidemia/methylenetetrahydrofolate reductase deficiency (5/28), and Charcot-Marie-tooth atrophy (1/28). Patients in the HSP group had chronic courses, most of whom were lower limbs spasticity, mainly with axonal neuropathy, and thinning corpus callosum, white matter lesions and cerebellar atrophy in brain MRI. In the non-HSP groups, upper and lower limbs both involvement was more common. Patients with homocysteine remethylation disorders or Krabbe’s disease or autosomal recessive spastic ataxia of Charlevoix-Saguenay had diagnostic results in laboratory or imaging examination. A total of 12 new variants were obtained.ConclusionsHSP had widespread clinical and genetic heterogeneity, and leukodystrophy, hereditary ataxia, Charcot-Marie-Tooth atrophy and homocysteine remethylation disorders accounted for a significant proportion of the proposed HSP. These diseases had different characteristics in clinical, laboratorial, electrophysiological, and radiological aspects, which could help differential diagnosis. Genetic analysis could ultimately provide a clear diagnosis, and broadening the scope of genetic testing could improve the positive rate of diagnosis.

Dynamic Relationship Between Interhemispheric Functional Connectivity and Corticospinal Tract Changing Pattern After Subcortical Stroke

Background and PurposeIncreased interhemispheric resting-state functional connectivity (rsFC) between the bilateral primary motor cortex (M1) compensates for corticospinal tract (CST) impairment, which facilitates motor recovery in chronic subcortical stroke. However, there is a lack of data on the evolution patterns and correlations between M1–M1 rsFC and diffusion indices of CSTs with different origins after subcortical stroke and their relations with long-term motor outcomes.MethodsA total of 44 patients with subcortical stroke underwent longitudinal structural and functional magnetic resonance imaging (MRI) examinations and clinical assessments at four time points. Diffusion tensor imaging was used to extract fractional anisotropy (FA) values of the affected CSTs with different origins. Resting-state functional MRI was used to calculate the M1–M1 rsFC. Longitudinal patterns of functional and anatomic changes in connections were explored using a linear mixed-effects model. Dynamic relationships between M1–M1 rsFC and FA values of the affected specific CSTs and the impact of these variations on the long-term motor outcomes were analyzed in patients with subcortical stroke.ResultsStroke patients showed a significantly decreased FA in the affected specific CSTs and a gradually increasing M1–M1 rsFC from the acute to the chronic stage. The FA of the affected M1 fiber was negatively correlated with the M1–M1 rsFC from the subacute to the chronic stage, FA of the affected supplementary motor area fiber was negatively correlated with the M1–M1 rsFC in the subacute stage, and FA of the affected M1 fiber in the acute stage was correlated with the long-term motor recovery after subcortical stroke.ConclusionOur findings show that the FA of the affected M1 fiber in the acute stage had the most significant correlation with long-term motor recovery and may be used as an imaging biomarker for predicting motor outcomes after stroke. The compensatory role of the M1–M1 rsFC enhancement may start from the subacute stage in stroke patients with CST impairment.

Detecting Corticospinal Tract Impairment in Tumor Patients With Fiber Density and Tensor-Based Metrics.

Tumors infiltrating the motor system lead to significant disability, often caused by corticospinal tract injury. The delineation of the healthy-pathological white matter (WM) interface area, for which diffusion magnetic resonance imaging (dMRI) has shown promising potential, may improve treatment outcome. However, up to 90% of white matter (WM) voxels include multiple fiber populations, which cannot be correctly described with traditional metrics such as fractional anisotropy (FA) or apparent diffusion coefficient (ADC). Here, we used a novel fixel-based along-tract analysis consisting of constrained spherical deconvolution (CSD)-based probabilistic tractography and fixel-based apparent fiber density (FD), capable of identifying fiber orientation specific microstructural metrics. We addressed this novel methodology’s capability to detect corticospinal tract impairment. We measured and compared tractogram-related FD and traditional microstructural metrics bihemispherically in 65 patients with WHO grade III and IV gliomas infiltrating the motor system. The cortical tractogram seeds were based on motor maps derived by transcranial magnetic stimulation. We extracted 100 equally distributed cross-sections along each streamline of corticospinal tract (CST) for along-tract statistical analysis. Cross-sections were then analyzed to detect differences between healthy and pathological hemispheres. All metrics showed significant differences between healthy and pathologic hemispheres over the entire tract and between peritumoral segments. Peritumoral values were lower for FA and FD, but higher for ADC within the entire cohort. FD was more specific to tumor-induced changes in CST than ADC or FA, whereas ADC and FA showed higher sensitivity. The bihemispheric along-tract analysis provides an approach to detect subject-specific structural changes in healthy and pathological WM. In the current clinical dataset, the more complex FD metrics did not outperform FA and ADC in terms of describing corticospinal tract impairment.

Corticospinal Tract Impairment of Patients With Parkinson's Disease: Triple Stimulation Technique Findings.

BackgroundCorticospinal tract impairment is no longer an absolute exclusion in the updated Movement Disorder Society Parkinson’s disease criteria. Triple stimulation technique (TST) is an accurate method to quantitatively assess the integrity and impairment of corticospinal pathway in a variety of neurological diseases. This study aims to evaluate the corticospinal tract impairment in Parkinson’s disease (PD) patients using TST.MethodsTen PD patients, 19 multiple-system atrophy parkinsonian variant (MSA-P) patients, and 12 healthy controls (HC) were sequentially recruited in this study. Information of age, disease duration, pyramidal signs, and Hoehn and Yahr (H&Y) stage was obtained from all patients. The TST was assessed at right abductor digiti minimi for HCs and both sides for patients. The Chi-square test was used for categorical variables, and variance analysis was performed for continuous variables in comparing the difference among PD, MSA-P, and HC, plus the post hoc tests for pairwise comparisons.ResultsAll subjects were age and gender matched. There was no significant difference in disease duration (p = 0.855), H-Y stage (p = 0.067), and the percentage of pyramidal signs present (p = 0.581) between MSA-P and PD patients. The mean TST ratio was 55.5 ± 32.2%, 81.7 ± 19.8%, and 96.8 ± 3.0% for PD, MSA-P, and HCs, correspondingly. PD patients had a significant lower TST amplitude ratio than MSA-P and HCs. The TST ratio of MSA-P was lower than HCs, but there was no significant difference (p = 0.160). Additionally, it was significantly higher in percentage of abnormal TST ratio between PD patients and MSA-P (p = 0.010).ConclusionCorticospinal tract impairment is not a rare manifestation in PD and can be quantitatively evaluated with TST. The result needs to be verified in amplified sample.

Enhanced interhemispheric functional connectivity compensates for anatomical connection damages in subcortical stroke.

Motor recovery after stroke has been shown to be correlated with both the fractional anisotropy (FA) of the affected corticospinal tract (CST) and the interhemispheric resting-state functional connectivity (rsFC) of the primary motor cortex (M1). However, the role of the restoration or enhancement of the M1-M1 rsFC in motor recovery remains largely unknown. We aimed to clarify this issue by investigating the correlations between the M1-M1 rsFC and the integrity of the M1-M1 anatomic connection and the affected CST in chronic subcortical stroke patients with good motor outcomes. Twenty patients and 16 healthy controls underwent multimodal magnetic resonance imaging examinations. Diffusion tensor imaging was used to reconstruct the M1-M1 anatomic connection and bilateral CSTs. White matter integrity of these tracts was assessed using FA. Resting-state functional magnetic resonance imaging was used to calculate M1-M1 rsFC. Group differences in these measures were compared. Correlations between M1-M1 rsFC and FA of the M1-M1 anatomic connection and the affected CST were analyzed in patients with stroke. Compared with healthy controls, patients with stroke exhibited significantly reduced FA in the affected CST and the M1-M1 anatomic connection and a significantly increased M1-M1 rsFC. The FA values of the affected CST were positively correlated with the M1-M1 anatomic connection, and these FA values were negatively correlated with the M1-M1 rsFC in these patients. Our findings suggest that the M1-M1 anatomic connection impairment is secondary to CST damage, and the M1-M1 rsFC enhancement may reflect compensatory or reactive neural plasticity in stroke patients with CST impairment.

Functional implications of corticospinal tract impairment on gait after spinal cord injury

Maximum toe elevation during walking is an objective measure of foot drop and reflects the impairment of the corticospinal tract (CST) in persons with spinal cord injury (SCI). To determine if this measurement is functionally relevant to ambulatory abilities, we correlated maximum toe elevation with clinical physiotherapy tests. Cross-sectional study, laboratory and clinical settings. A total of 24 individuals with SCI (American Spinal Injury Association (ASIA) Impairment Scale D) were recruited. Maximum toe elevation during the swing phase of treadmill gait was measured with a kinematic system. CST function was assessed in a sitting position by measuring the motor-evoked potentials (MEPs) induced in tibialis anterior muscle with transcranial magnetic stimulation over the motor cortex. Clinical tests performed were 10-m and 6-min walk test (6MWT), Timed-Up and Go (TUG), Walking Index for Spinal Cord Injury, Berg Balance Scale, Lower Extremity Motor Score (LEMS) and sensory score of the L4, L5 and S1 dermatomes. Participants with lower toe elevation during gait walked at a slower speed, took more time to perform the TUG test, and covered a shorter distance in the 6MWT. They also scored lower on the LEMS and showed impaired superficial sensitivity of the dermatomes around the ankles. Few correlations were observed between CST function and clinical tests, but the presence of MEP at rest was indicative of faster speed and longer distance in the 6MWT. These results indicate that maximum toe elevation, which is directly correlated with CST impairment, is functionally relevant as it also correlates with timed clinical tests, LEMS and sensory scores.

Abstract 2856: Lesion load of Corticospinal Tract and Initial Motor Impairment in the Acute Stroke Phase Predict Motor Impairment 3 Months Post-Stroke

Background: We use lesion-mapping techniques in combination with diffusion tensor imaging to quantitatively test the hypothesis that motor impairment 3 months post- stroke is inversely related to the lesion load of the corticospinal tract (CST) in the acute stroke phase. Methods: We prospectively followed up a cohort of 32 patients who presented with their first-ever acute ischemic stroke with various degree of motor deficit , had a MRI during the hospitalization, and had follow-up motor assessments using the Fugl-Meyer Upper Extremity Scale (FM-UE) at 3 months (+/- 2 weeks) after stroke. We calculated a CST-lesion load for each patient by overlaying the patient’s lesion map from diffusion weighted image with a probabilistic DTI tract constructed from 12 age-matched healthy subjects . Both raw and weighted (which accounts for the narrowing of the CST as it descends from the motor cortex to the posterior limb of the internal capsule) were calculated; weighted lesion-loads were calculated by multiplying the lesion-tract overlap on each slice by the ratio of the maximum cross-sectional area of the tract to the cross-sectional area of the tract on that particular slice). A multiple regression is fit to assess the predicted value of CST lesion load (raw or weighted), along with other variables such age, gender, lesion size, initial impairment, days of therapy known to have an possible effect on motor outcome. Results: CST-lesion load and initial motor impairment are found to be significant predictors of upper extremity motor impairment at 3 months post-stroke. Age, gender, lesion size or days of therapy does not have predictive value in our cohort study. The adjusted R² is 0.63 with initial impairment and raw lesion load in the regression model, and is 0.66 with initial impairment and weighted lesion load. Conclusions: Our data shows the degree of motor impairment at 3 months after a first-ever ischemic stroke can be predicted by the overlap of the lesion with the canonical CST derived from age-matched healthy control subjects and the initial motor impairment measured in the acute phase.

*Poster 43: Gait Deficits Due to Impairment of the Corticospinal Tract in Persons With Incomplete Spinal Cord Injury

Objective: To investigate whether the extent of corticospinal tract (CST) impairment may explain the degree of foot drop in persons with spinal cord injury (SCI). Design: Open experimental study with 1 session where gait function and transmission in CST was assessed and 1 session where clinical tests were performed. Setting: Data were collected in a research laboratory and an SCI physiotherapy department. Participants: 24 SCI and 17 control participants. Interventions: Not applicable. Main Outcome Measures: Foot drop was determined during treadmill gait by measuring the toe elevation during swing phase and ankle angular excursion in the first part of swing with a kinematic analysis system.

Evaluation of Corticospinal Tract Impairment in the Brain of Patients With Amyotrophic Lateral Sclerosis by Using Diffusion Tensor Imaging Acquisition Schemes With Different Numbers of Diffusion-Weighting Directions

Amyotrophic lateral sclerosis is characterized by degeneration of upper and lower motor neurons. Diffusion tensor imaging (DTI) indexes obtained along the corticospinal tracts distinguish ALS patients and control subjects. Diffusion tensor imaging can be estimated from at least 6 diffusion-weighted images; however an acquisition scheme with a higher number of diffusion directions allows a more robust estimation of DTI indexes. The aim of the study was to establish if a higher number of diffusion encoding gradients increases the diagnostic accuracy of DTI in ALS. We studied 18 patients and 16 control subjects acquiring 2 DTI data sets with 6 and 31 gradient orientations. The mean diffusivity and fractional anisotropy values were measured along the corticospinal tract. Mean diffusivity in ALS was significantly increased (P = 0.026) with respect to control subjects in acquisition scheme with 31 but not (P = 0.214) with 6 diffusion-weighting directions. Fractional anisotropy was significantly lower in patients both with 6 (P = 0.0036) and with 31 (P = 0.0004) diffusion-weighting directions (0.538 vs 0.588 and 0.530 vs 0.594). Fractional anisotropy receiver operating characteristic curve analysis showed a higher diagnostic accuracy by using 31 diffusion-weighting direction (85.76%) with respect to 6 directions (79.86%). Diffusion tensor imaging confirms its potentials in diagnosing ALS with a good accuracy; the acquisition scheme with a higher diffusion-weighting directions seems to better discriminate between ALS patients and control subjects.

Case Study: Rating Syringomelia by Fifth Edition

Case Study: Rating Syringomelia by Fifth Edition

Diffusion weighted imaging in ataxic hemiparesis

Objective:Ataxic hemiparesis (AH) is a well recognised lacunar syndrome involving homolateral ataxia with accompanying corticospinal tract impairment. Most previous studies of lesion location in AH did not use diffusion weighted...

Assessment of cortico-spinal tract impairment in multiple system atrophy using transcranial magnetic stimulation

Objective Among Parkinsonian syndromes, pyramidal signs suggesting cortico-spinal impairment are a hallmark of multiple system atrophy (MSA). Although it is crucial to diagnose correctly this disease to choose the appropriate treatment, the available diagnostic criteria lack sensitivity. Cortical excitability patterns assessed by transcranial magnetic stimulation (TMS) do not differentiate Parkinsonian disorders. TMS using triple stimulation technique (TST) accurately detects cortico-spinal impairment. We hypothesized that this technique could detect such impairment in MSA patients. Methods The TST was applied along with single and paired-pulse TMS to 31 patients fulfilling the diagnostic criteria for MSA-P ( n = 10), MSA-C ( n = 4), progressive supranuclear palsy (PSP; n = 6) and Idiopathic Parkinson’s disease (IPD; n = 11) and 11 control subjects. Results Single and paired-pulse TMS patterns did not differ between any patient group. The TST pattern was abnormal in five MSA-P, one MSA-C and one PSP patients but not in IPD patients or controls. The mean TST ratio for MSA-P (86.6%) was significantly different from IPD (99.1%; p < 0.05) whereas ratios for MSA-C (92.1%) and PSP (93.3%) were not different from IPD or controls (99.5%). Conclusions These results suggest that TST is effective to assess cortico-spinal impairment in MSA. Significance TST might be useful for the diagnosis of atypical Parkinsonism.

Diffusion-Tensor MR Imaging of Corticospinal Tract in Amyotrophic Lateral Sclerosis and Progressive Muscular Atrophy

To prospectively evaluate several diffusion-tensor magnetic resonance (MR) imaging indexes (mean diffusivity [MD], fractional anisotropy [FA], and eigenvalues) of corticospinal tract impairment in patients with progressive muscular atrophy (PMA) and patients with amyotrophic lateral sclerosis (ALS). This study had institutional review board approval, and written informed consent was obtained from all subjects. Eight male patients with PMA (mean age, 63 years +/- 13 [standard deviation]), eighteen patients with ALS (14 men and four women; mean age, 64 years +/- 7), and twelve control subjects (four men and eight women; mean age, 65 years +/- 6) underwent diffusion-tensor MR imaging at which 25 spin-echo echo-planar imaging diffusion-weighted images (b = 1000 sec/mm2) were acquired along noncollinear directions. MD and FA were measured along the corticospinal tracts in each patient and subject. Changes in diffusion along and orthogonal to fiber bundles in patients were evaluated by using diffusion-tensor eigenvalues. Differences in diffusion-tensor imaging indexes between patients with PMA and those with ALS, as compared with these indexes in control subjects, were evaluated with Mann-Whitney testing. Correlations between diffusion-tensor imaging indexes and clinical variables were estimated with Pearson and Spearman rank correlation testing. As compared with MD (697.1 x 10(-6) mm2/sec +/- 28.1) and FA (0.585 +/- 0.032) in control subjects, MD was typically significantly increased (734.7 x 10(-6) mm2/sec +/- 41.2, P = .035) and FA significantly decreased (0.534 +/- 0.053, P = .037) along the corticospinal tracts in patients with ALS, while these parameters showed no significant change in patients with PMA (MD, 707.0 x 10(-6) mm2/sec +/- 44.2; FA, 0.559 +/- 0.028). Estimation of diffusion-tensor eigenvalues revealed normal diffusion along fiber tracts in all patients, while diffusion was increased orthogonal to fiber tracts only in patients with typical ALS. In patients with ALS, MD correlated with disease duration while FA correlated with disease severity. Diffusion-tensor MR imaging reveals corticospinal tract impairment in ALS but not in PMA.

Lumbosacral Corticospinal and Cauda Equina Injuries

Abstract Spinal cord injuries can affect many functions, interfere with the activities of daily living, and result in significant impairment. This article reviews cauda equina and conus medullaris syndromes, examines the process of rating corticospinal tract damage, and provides a case example. In the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), cauda equina syndrome refers to the polyradicular symptomatology resulting from single- or double-level compression of the lumbosacral nerve roots in the dural sac and may include low-back pain, saddle anesthesia, sciatica, motor weakness of the lower extremities, chronic paraplegia, and bladder, bowel, or sexual dysfunction. Conus medullaris syndrome is caused by a compression injury at T12 or L1, and flaccid paralysis of the legs and anal sphincter with variable sensory deficits may be present. The AMA Guides, Fifth Edition, includes Table 15-6, Rating Corticospinal Tract Impairment, which presents criteria for rating the neurological impairment. The physician must determine which systems are impaired, then which categories are appropriate and what value within a range should be selected. This requires the use of judgment because large ranges are provided. Spinal injuries that involve corticospinal tract damage are assessed using the Diagnosis-related estimate (DRE) method, but the range-of-motion method can be used in specified situations. A case example demonstrates how to assess neurological impairment.

Neurologic semiology of a group of first grade students in an elementary school

We evaluated children in the first grade of a elementary school using neurological examination. With no previous knowledge of their educational performance, were invited all children attending five classes of the first grade of an elementary public school chosen randomly, in Itatiba / Sao Paulo / Brazil, whose parents assigned a Commitment Term for participation in this research. Children who missed three evaluations in different days or whose parents did not assigned the Commitment Term were excluded. The Traditional Neurological Examination (ENT) (Lefevre, 1972) was applied. It was considered for normal the measurement of the skull circumference, proposed by Diament & Rodrigues (1976), and the application of all ENT items. The data were stored in a database of the Epi6 Program (Epidemiologic Information), and analyzed by percentage calculation and by the chi2 test. The significance level was 0.05. Children evaluated were 124. The ENT results were normal in 87 (70.16%) and altered in 37 (29.83%). Among the alterations, there were observed: light tremor, light muscular hypotonia, speech acquisition delay, macrocephaly, microcephaly, hyperactivity, cranial nerve syndrome, central facial paralysis. One child presented corticospinal tract impairment syndrome of the distal lower extremities.

Ataxic hemiparesis: critical appraisal of a lacunar syndrome.

Ataxic hemiparesis is a well-recognized lacunar syndrome involving homolateral ataxia with accompanying corticospinal tract impairment. Despite 30 years of clinical experience there continues to be some doubt as to the defining clinical characteristics, precise neuroanatomic localization of the syndrome, and etiologic mechanisms. We now present 45 new cases that have been analyzed for clinico-radiologic correlation and etiology. Also, all published cases from the English literature known to the authors are reviewed. We found that the clinical syndrome of ataxic hemiparesis accurately predicts a small deep infarction, generally in the pons or internal capsule. Sensory loss is highly associated with a capsular localization. We found that 47% of the cases were attributed to small-vessel disease, 11% to cardioembolism, and only 7% to artery-to-artery embolism (all in the basilar artery); 1 case was attributed to thrombocytosis, 1 to multiple sclerosis, and the rest either had negative or incomplete evaluation. Approximately two thirds of the infarctions occurred in patients with neuroimaging evidence of other ischemic brain lesions. Ataxic hemiparesis is a distinct clinical syndrome that accurately predicts a small deep infarction, most commonly in the pons or internal capsule. Only sensory loss accurately predicts a capsular localization. Etiology in nearly half of the cases can be attributed to small-vessel disease. Furthermore, ataxic hemiparesis appears to be a good marker for generalized asymptomatic cerebrovascular disease.