A repeating fast radio burst source localized to a nearby spiral galaxy.

Fast radio bursts (FRBs) are brief, bright, extragalactic radio flashes1,2. Their physical origin remains unknown, but dozens of possible models have been postulated3. Some FRB sources exhibit repeat bursts4-7. Although over a hundred FRB sources have been discovered8, only four have been localized and associated with a host galaxy9-12, and just one of these four is known to emit repeating FRBs9. The properties of the host galaxies, and the local environments of FRBs, could provide important clues about their physical origins. The first known repeating FRB, however, was localized to a low-metallicity, irregular dwarf galaxy, and the apparently non-repeating sources were localized to higher-metallicity, massive elliptical or star-forming galaxies, suggesting that perhaps the repeating and apparently non-repeating sources could have distinct physical origins. Here we report the precise localization of a second repeating FRB source6, FRB 180916.J0158+65, to a star-forming region in a nearby (redshift 0.0337 ± 0.0002) massive spiral galaxy, whose properties and proximity distinguish it from all known hosts. The lack of both a comparably luminous persistent radio counterpart and a high Faraday rotation measure6 further distinguish the local environment of FRB 180916.J0158+65 from that of the single previously localized repeating FRB source, FRB 121102. This suggests that repeating FRBs may have a wide range of luminosities, and originate from diverse host galaxies and local environments.

Effects of unilateral stroke on multi-finger synergies and their feed-forward adjustments.

We explored the changes in multi-finger synergies in patients after a single cortical stroke with mild motor impairments. We hypothesized that both synergy indices and anticipatory synergy adjustments prior to the initiation of a self-paced quick action would be diminished in the patients compared to age-matched controls. The patients with history of cortical stroke, and age-matched controls (n=12 in each group) performed one-finger and multi-finger accurate force production tasks involving both steady-state and quick force pulse production. Finger interdependence (enslaving) and multi-finger synergies stabilizing total force were quantified. The stroke patients showed lower maximal finger forces, in particular in the contralesional hand, which also showed increased enslaving indices. Multi-finger synergies during steady-state force production were, however, unchanged after stroke. In contrast, a drop in the synergy index prior to the force pulse generation was significantly delayed in the stroke patients. Our results show that mild cortical stroke leads to no significant changes in multifinger synergies, but there is impairment in feed-forward adjustments of the synergies prior to a quick action, a drop in the maximal force production, and an increase in enslaving. We conclude that studies of synergies reveal two aspects of synergic control differentially affected by cortical stroke.

Open-label dose-titration safety and efficacy study of tizanidine hydrochloride in the treatment of spasticity associated with chronic stroke.

BACKGROUND AND PURPOSE: Spasticity is a frequently observed motor impairment that develops after stroke; it can cause pain and disability in those affected. The objective of the present study was to evaluate the safety and efficacy of tizanidine, a centrally acting alpha(2)-adrenergic agonist, in the treatment of stroke-related spasticity. METHODS: Forty-seven patients, who were a minimum of 6 months poststroke and had significant spasticity, were studied at 4 centers. Tizanidine was administered in an open-label manner for 16 weeks, beginning at 2 mg/d and slowly titrated to a maximum of 36 mg/d. The Modified Ashworth Scale, muscle strength testing, functional assessments, and Pain and Functional Spasticity Questionnaires were administered at baseline and at 4, 8, 16, and 18 weeks (after 1 week off tizanidine). RESULTS: Spasticity was significantly improved between baseline and week 16, with a decrease in total upper extremity Modified Ashworth Scale score of 2.80+/-0.47 (P<0.0001). No decline in strength was noted. Treatment with tizanidine resulted in a significant improvement in pain intensity (P=0.0375), quality of life (P=0.0001), and physician assessment of disability (P=0.0001). The most frequent side effects were somnolence (62%) and dizziness (32%). No serious adverse events were considered to be drug related. Ten of 47 patients (21%) were able to reach the maximum daily dosage of 36 mg. CONCLUSIONS: Overall, the data suggest that tizanidine is safe and efficacious in the treatment of stroke-related spasticity, preserving muscle strength while reducing muscle tone and painful spasms in affected patients.

Pathologic changes associated with intracranial hypotension and meningeal enhancement on MRI.

We report a patient with a 6-week history of postural headache due to intracranial hypotension whose MRI revealed findings typical of this syndrome, including diffuse meningeal enhancement following gadolinium infusion. Biopsy revealed extensive fibrocollagenous proliferation in the leptomeninges without evidence of inflammation. The pathologic changes in this patient, which occurred soon after the onset of symptoms, are probably related to the striking meningeal enhancement seen in this syndrome.

Indications for echocardiography in patients with ischemic stroke.

The recent availability of two-dimensional echocardiography (2DE) has fostered the expectation that cardiac embolic sources could be identified or excluded with certitude in ischemic stroke patients. As a screening procedure, 2DE has had a low yield. In selected patients, 2DE holds promise as a useful diagnostic test. Stroke patients who may benefit from 2DE include patients under age 45, patients with suspected left atrial myxoma, and patients with known infective endocarditis, prosthetic heart valves, or rheumatic valvular heart disease. In patients with ischemic heart disease, the yield of useful information from 2DE will be low but may, on occasion, influence management.

Co-registration of cortical magnetic stimulation and functional magnetic resonance imaging.

Functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) are noninvasive techniques recently used to investigate cortical motor physiology. However, these modalities measure different phenomena, and in studies of human motor control they have given inconsistent results. We have developed a reproducible technique which co-registers TMS and fMRI, using a frameless method. In four normal subjects, the TMS map and fMRI activation were present on the primary motor cortex contralateral to the target hand, with some extension into primary sensory cortex. fMRI activation alone was also present in the medial motor cortex bilaterally and in the sensorimotor cortex ipsilateral to the target hand. This technique allows a more comprehensive evaluation of the physiologic events involved in motor control.

Measurement of lingual and palatine somatosensory evoked potentials.

OBJECTIVE: A technique is presented for generating and recording lingual and palatine nerve somatosensory evoked potentials (SEPs). METHODS: Pairs of thin, stainless steel disk electrodes were mounted onto mandibular or maxillary acrylic splints, similar to orthodontic retainers. Mandibular splint electrodes were oriented to contact the under surface of the tongue along the course of the right and left lingual nerves and maxillary splint electrodes were oriented to contact the hard palate bilaterally along the course of the palatine nerves. SEP recording electrodes were placed on the scalp 1 cm posterior to C5 and C6 (C5' and C6', respectively) using the combinatorial nomenclature of the International 10-20 system. Two reference electrode locations, Fz and C5' or C6', over the cortical hemisphere opposite that of the recording electrode, were used. RESULTS: Right and left lingual and palatine nerve SEPs were recorded from five normal adults. SEP latencies were similar to the N13 and P18 cortical peak latencies recorded in previous studies of trigeminal nerve branches to the lips regardless of reference electrode position. CONCLUSIONS: A more precise method of stimulating the intraoral lingual and palatine nerves was accomplished using dental splints. SEPs were easier to obtain using a contralateral cortex reference electrode location.

Visualization of brain iron by mid-field MR.

Brain iron was visualized on a mid-field (0.5 T) scanner using a spin-echo pulse sequence. Methemoglobin was hyperintense on T1- and T2-weighted images. Deoxyhemoglobin, hemosiderin, and ferritin were seen as decreased intensity on T2-weighted images. The spin-echo pulse sequences were improved for identification of deoxyhemoglobin, hemosiderin, and ferritin by prolonging the TR to 3000 msec and the TE to 80-120 msec. Phase-encoding artifacts at the level of the sylvian fissures caused increased noise, obscuring the brain iron in the lentiform nuclei with the TE of 120 msec. This artifact was substantially reduced or eliminated by lowering the TE to 80 msec, changing the phase-encoding gradient to the Y axis, or using additional pulsing in the slice and read gradients. Use of either the improved spin-echo or gradient-echo pulse sequences on a mid-field MR scanner provides improved evaluation of brain iron.

Quantitative measurement of neurologic impairment in patients with multiple sclerosis.

Eleven patients with clinically diagnosed multiple sclerosis were simultaneously evaluated with history, physical, and neurologic evaluations and a series of objective neurophysiologic tests. Patients were then scored independently on clinical stage of their disease using a system based on symptoms in history or findings on physical or neurologic examination. Test scores on objective tests were compared with clinical scores with each evaluator. Patients with high test scores on clinical evaluation usually had high test scores on objective testing. Symptoms and physical findings were then correlated with abnormalities on objective tests. Objective abnormalities in visual evoked response and auditory evoked response on several occasions preceded the development of symptoms. All patients except for two had more than one abnormality on objective testing, suggesting a high likelihood that objective tests are helpful in the diagnosis of early-stage multiple sclerosis.

"Numb, clumsy hands" and high cervical spondylosis.

Thirteen patients with cervical spondylosis and high compressive myelopathy between C-3 and C-5 presented with a distinctive clinical syndrome of "numb, clumsy hands" and stereoanesthesia of the hands. Loss of position and vibration sense was much more severe in the hands than in the legs. Relative sparing of primary sensory modalities and motor and bladder functions were other features. Most patients were incorrectly diagnosed at first and cervical myelography was the critical diagnostic test. Pathology was confirmed surgically or at autopsy. Early recognition and treatment resulted in lessened disability. The syndrome is a distinctive and unusual manifestation of high cervical myelopathy, and it has seldom been reported associated with cervical spondylosis.

Examining network dynamics after traumatic brain injury using the extended unified SEM approach.

The current study uses effective connectivity modeling to examine how individuals with traumatic brain injury (TBI) learn a new task. We make use of recent advancements in connectivity modeling (extended unified structural equation modeling, euSEM) and a novel iterative grouping procedure (Group Iterative Multiple Model Estimation, GIMME) in order to examine network flexibility after injury. The study enrolled 12 individuals sustaining moderate and severe TBI to examine the influence of task practice on connections between 8 network nodes (bilateral prefrontal cortex, anterior cingulate, inferior parietal lobule, and Crus I in the cerebellum). The data demonstrate alterations in networks from pre to post practice and differences in the models based upon distinct learning trajectories observed within the TBI sample. For example, better learning in the TBI sample was associated with diminished connectivity within frontal systems and increased frontal to parietal connectivity. These findings reveal the potential for using connectivity modeling and the euSEM to examine dynamic networks during task engagement and may ultimately be informative regarding when networks are moving in and out of periods of neural efficiency.

Changes in resting connectivity during recovery from severe traumatic brain injury.

In the present study we investigate neural network changes after moderate and severe traumatic brain injury (TBI) through the use of resting state functional connectivity (RSFC) methods. Using blood oxygen level dependent functional MRI, we examined RSFC at 3 and 6 months following resolution of posttraumatic amnesia. The goal of this study was to examine how regional off-task connectivity changes during a critical period of recovery from significant neurological disruption. This was achieved by examining regional changes in the intrinsic, or "resting", BOLD fMRI signal in separate networks: 1) regions linked to goal-directed (or external-state) networks and 2) default mode (or internal-state) networks. Findings here demonstrate significantly increased resting connectivity internal-state networks in the TBI sample during the first 6 months following recovery. The most consistent finding was increased connectivity in both internal and external state networks to the insula and medial temporal regions during recovery. These findings were dissociable from repeat measurements in a matched healthy control sample.

Rehabilitation of the stroke patient.

Research into stroke rehabilitation is an active area of investigation, and ample evidence suggests that patients with moderate deficits benefit from focused rehabilitation programs. Increasing age, stroke severity, and neuropsychological deficits are associated with a poor outcome. In this review we will discuss the most recent literature on stroke rehabilitation, with special emphasis on outcome predictors, motor recovery, and therapeutic strategies for aphasia and neuropsychological deficits.

Cardiac abnormalities in stroke patients with negative arteriograms.

Sixty-five consecutive patients with recent unequivocal TIA (33) or stroke (32), but nondiagnostic arteriograms, had two-dimensional echocardiograms (2DE) and electrocardiograms (ECG) to determine the incidence of cardiac abnormalities which could cause embolic stroke. Abnormalities were classified according to increasing probability of causing an embolic event: non-specific, possible emboligenic abnormality (PEA) or definite emboligenic abnormality (EA). Although 2DE was abnormal in 33 patients (51%), and ECG in 38 (59%), many abnormalities were nonspecific. Only four patients (6%) had EA on ECG and two (3%) on 2DE. Since one patient had EA on both tests, 2DE identified only one patient (mitral valve prolapse) not already identified by ECG. All patients with EA had a prior history of cardiac disease. PEA was present on ECG in 11 patients (17%), and on 2DE in 25 (38%). There was no correlation between age, CT results, or neurologic symptoms commonly associated with embolic stroke and the presence of EA or PEA on ECG or 2DE. Although TIA and stroke patients with negative arteriograms have a high incidence of abnormalities on ECG and 2DE, the percentage of patients with EA is low, and cardiac history and ECG identify most patients. 2DE provides little additional information.

Causes of urinary incontinence after acute hemispheric stroke.

BACKGROUND AND PURPOSE: We prospectively studied bladder function in stroke patients to determine the mechanisms responsible for poststroke urinary incontinence. METHODS: Fifty-one patients with recent unilateral ischemic hemispheric stroke admitted to a neurorehabilitation unit were enrolled. The presence of urinary incontinence was correlated with infarct location, neurological deficits, and functional status. Urodynamic studies were performed on all incontinent patients. RESULTS: Nineteen patients (37%) were incontinent. Incontinence was associated with large infarcts, aphasia, cognitive impairment, and functional disability (p < 0.05) but not with age, sex, side of stroke, or time from stroke to entry in the study. Urodynamic studies, performed on all 19 incontinent patients, revealed bladder hyperreflexia in 37%, normal studies in 37%, bladder hyporeflexia in 21%, and detrusor-sphincter dyssynergia in 5%. All of the patients with normal urodynamic studies were aphasic, demented, or severely functionally impaired. All of the patients with hyporeflexic bladders had underlying diabetes or were taking anticholinergic medications. Forty-six percent of incontinent patients treated with scheduled voiding alone were continent at discharge compared with 17% of patients treated pharmacologically. CONCLUSIONS: There are three major mechanisms responsible for poststroke urinary incontinence: 1) disruption of the neuromicturition pathways, resulting in bladder hyperreflexia and urgency incontinence; 2) incontinence due to stroke-related cognitive and language deficits, with normal bladder function; and 3) concurrent neuropathy or medication use, resulting in bladder hyporeflexia and overflow incontinence. Urodynamic studies are of benefit in establishing the cause of incontinence. Scheduled voiding is a useful first-line treatment in many cases of incontinence.

Sleep-disordered breathing and poor functional outcome after stroke.

BACKGROUND AND PURPOSE: We objectively evaluated patients with recent stroke to determine the prevalence of sleep-disordered breathing (SDB) and whether SDB was associated with unfavorable clinical outcomes. METHODS: Forty-seven patients with recent ischemic stroke (median, 13 days) were studied with computerized overnight oximetry for evidence of arterial oxyhemoglobin desaturation (SaO2). Polysomnography was also performed on 19 patients. Medical history, sleep history, location of stroke, and severity of neurological deficit were recorded, and patients were observed by staff for evidence of snoring and excessive daytime sleepiness. Functional abilities were measured with the use of the Barthel Index (BI). Outcome variables included ability to return home at discharge, continued residence at home at 3 and 12 months, BI at discharge, BI at 3 and 12 months, and death from any cause at 12 months. RESULTS: Mean SaO2 during oximetry was 94.0 +/- 1.7%, and percentage of recording time spent at < 90% SaO2 was 4.3 +/- 5.7%. The number of desaturation events per hour of recording time (desaturation index [DI]) was 9.5 +/- 9.67, with 15 of 47 (32%) having DI > 10 and 6 of 47 (13%) having DI > 20. Oximetry measures of SDB correlated with lower BI scores at discharge and lower BI at 3- and 12-month follow-ups (P < or = .05, Pearson coefficients). Oximetry measures correlated with return home after discharge, but the association between oximetry measures and living at home was lost at 12 months. Two oximetry variables correlated with death at 1 year. Brain stem location correlated with higher DI and time at < 90% SaO2, but patients with hemispheric stroke and oximetry abnormalities also had worse functional outcome. No correlation was found between oximetry values and sex, age, preexisting medical conditions (except previous stroke), or severity of neurological deficit. Oximetry abnormalities were associated with a history of snoring. Polysomnography on 19 patients confirmed oximetry evidence of severe SDB. Eighteen of 19 patients (95%) had an apnea-hypopnea index (AHI) of > 10 events per hour of recording, 13 of 19 (68%) had an AHI > 20, and 10 of 19 (53%) had an AHI > 30. Desaturation events were largely due to obstructive apneas. CONCLUSIONS: SDB accompanied by arterial oxyhemoglobin desaturation is common in patients undergoing rehabilitation after stroke and is associated with higher mortality at 1 year and lower BI scores at discharge and at 3 and 12 months after stroke. SDB may be an independent predictor of worse functional outcome. Obstructive sleep apnea appeared to be the most common form of SDB, and the frequent history of snoring suggests that SDB preceded the stroke in most patients.

Brainstem auditory and visual evoked potentials in type 1 (insulin-dependent) diabetic patients.

Brainstem auditory evoked potentials and pattern shift visual evoked potentials were measured in 34 Type 1 (insulin-dependent) diabetic patients with long-standing disease and in 43 control subjects. Thirty-two percent of diabetic patients had abnormal brainstem auditory evoked potentials and 15% had abnormal visual evoked potentials. These abnormalities were not related to duration of diabetes, diabetic control or individual diabetic complications (retinopathy, nephropathy, peripheral or autonomic neuropathy). The aetiology of the abnormalities must remain a subject for speculation. The findings of this study are consistent with a central diabetic neuropathy involving the brainstem in long-standing diabetic patients.

Echocardiography in diagnostic assessment of stroke.

We assessed the use of echocardiography in the evaluation of stroke by recording M-mode and two-dimensional (2D) echocardiograms in 100 consecutive hospitalized patients. Of the 95 persons satisfactorily imaged with 2D echocardiography, 47 lacked clinical and routine laboratory evidence of heart disease; no potential embolic source or other finding that altered therapy was diagnosed by echocardiography. In the remaining 48 patients with clinical or routine laboratory evidence of heart disease, two with left ventricular thrombus as a potential embolic source were identified by 2D echocardiography. M-mode echocardiograms failed to detect the thrombus in either patient. No patients with left atrial thrombi, mitral stenosis, cardiac tumor, or vegetations suggesting endocarditis were identified. One patient had possible mitral valve prolapse. Echocardiograms in patients lacking other available evidence of heart disease are unlikely to yield findings that alter the clinical approach to patients with stroke; echocardiography in stroke patients with clinically evident heart disease may have greater clinical utility; additional study of the role of echocardiography in selected subgroups of stroke patients is indicated.