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Introduction: Collateral circulation plays a crucial role in determining the extent of brain tissue ischemia and functional outcome in large vessel occlusive (LVO) stroke. Heart failure (HF) is known to cause cerebral hypoperfusion, yet the relationship between HF and robustness of collateral flow has not been well described. Here we hypothesized that HF is associated with poor collateral flow and functional outcome in patients presenting with LVO treated with mechanical thrombectomy (MT). Methods: A single center retrospective study of patients presenting with LVO ischemic stroke who underwent MT between 2012-2020 was done. Single-phase CTA of head prior to MT was used to assess collateral status with poor status defined as ≤ 50% filling and good status as >50% filling. Classification of HF by left ventricular ejection fraction (LVEF) on echocardiogram was used where HF with reduced ejection fraction (HFrEF) had LVEF ≤40%, HF with preserved EF (HFpEF) had LVEF ≥50% with evidence of structural heart disease, and no HF was LVEF≥50% without structural heart disease. Functional outcome was modified Rankin scale (mRS) at 90 days with scores of 0-2 representing good outcome and 3-6 representing poor outcome. Multivariable logistic regression analyses were performed to evaluate the association between HF and poor collaterals after adjusting for vascular risk factors. Results: We identified 235 patients, mean age was 69 ±15 years, median NIHSS was 18, and 45.5% had HF (HFrEF 12.8%, HFmrEF 4.7%, HFpEF 28.1%) while 54.5% had no HF. Poor collaterals were seen in 47.7%, and those with HF were likely to have poor collaterals compared to those without HF (56.1% vs 35.1%, P=.001). There was a dose-dependent relationship between severity of HF and poor collaterals: adjusted odds of poor collaterals were 1.63 and 2.45 in HFpEF and HFrEF, compared to those without HF (trend p=.018). Patients with poor collaterals were likely to have poor outcome at 3 months compared to those with good collaterals (75.0% vs 57.8%; p=.015). Conclusion: Patients with HFrEF were twice as likely to have poor collaterals. This study demonstrated a likely mechanism for poor outcomes seen in ischemic stroke with HF, future studies may explore whether optimization of HF may augment collaterals to improve outcomes.

Objective Neurosurgical patients are at a higher risk of having a severe course of coronavirus disease 2019 (COVID-19). The objective of this study was to determine morbidity, hospital course, and mortality of neurosurgical patients during the coronavirus disease 2019 (COVID-19) pandemic in a multicenter health care system. Methods A retrospective observational study was conducted to identify all hospitalized neurosurgical patients positive for COVID-19 from March 11, 2020 to November 2, 2020 at Mayo Clinic and the Mayo Clinic Health System. Results Eleven hospitalized neurosurgical patients (0.68%) were positive for COVID-19. Four patients (36.6%) were men and 7 (63.3%) were women. The mean age was 65.7 years (range, 35–81 years). All patients had comorbidities. The mean length of stay was 13.4 days (range, 4–30 days). Seven patients had a central nervous system malignancy (4 metastases, 1 meningioma, 1 glioblastoma, and 1 schwannoma). Three patients presented with cerebrovascular complications, comprising 2 spontaneous intraparenchymal hemorrhages and 1 ischemic large-vessel stroke. One patient presented with an unstable traumatic spinal burst fracture. Four patients underwent neurosurgical/neuroendovascular interventions. Discharge disposition was to home in 5 patients, rehabilitation facility in 3, and hospice in 3. Five patients had died at follow-up, 3 within 30 days from COVID-19 complications and 2 from progression of their metastatic cancer. Conclusions COVID-19 is rare among the inpatient neurosurgical population. In all cases, patients had multiple comorbidities. All symptomatic patients from the respiratory standpoint had complications during their hospitalization. Deaths of 3 patients who died within 30 days of hospitalization were all related to COVID-19 complications. Neurosurgical procedures were performed only if deemed emergent.

Transient ischemic attack (TIA) has gained significant attention recently due to the increased incidence of subsequent stroke. However, there are many nonvascular clinical mimics of TIA, creating a need for improved biomarkers to identify a vascular origin. Following the recent approval of ultra-high field (UHF) 7T MRI in clinical practice, several clinical studies have highlighted its added utility in neuroimaging compared to lower-field 1.5T and 3T MRI, particularly in epilepsy and multiple sclerosis. Our case series of three patients with TIA illustrates that 7T MRI can depict small areas of intracortical microhemorrhages and microinfarctions, which could not be resolved with 3T or 1.5T MRI. There are currently no reports of intracortical localization of microhemorrhages in patients with TIA. This discovery may enhance our understanding and characterization of cerebrovascular abnormalities in TIAs. In addition, UHF imaging could potentially be utilized to distinguish transient neurological episodes secondary to cerebrovascular events from other differential considerations. Our cases highlight the underestimation of imaging abnormalities in cases of TIA and support the potential expanded application of clinical 7T to assess patients with TIA. Future studies are necessary at 7T redundant to determine the true incidence of such lesions in TIA and to examine the correlation between cortical microhemorrhages and subsequent ischemic stroke, hemorrhagic events, and neurocognitive impairment.

Background: With increasing demand for neurologists, nontraditional health care delivery mechanisms have been developed to leverage this limited resource. Introduction: Telemedicine has emerged as ...

3D time-of-flight (TOF) MR angiography (MRA) benefits from ultra-high-field MRI (≥7 T) due to improved contrast and increased signal-to-noise ratio. However, high-resolution TOF MRA at 7T usually requires longer acquisition times. In addition, relatively higher specific absorption rate (SAR) at 7T limits the choice of optimal pulse sequence parameters, especially if venous saturation is employed. Here, we illustrate the clinical application of ultra-high resolution cerebral 7T TOF MRA using compressed sensing in cases of artery of Percheron and lacunar infarcts, which showed superior resolution and exquisite details pertinent to the clinical diagnosis. The technical challenges associated with high-resolution 7T imaging were alleviated by optimization of sequence parameters and utilization of compressed sensing acceleration.

CNS small vessel disease (CSVD) causes 25% of strokes and contributes to 45% of dementia cases. Prevalence increases with age, affecting about 5% of people aged 50 years to almost 100% of people older than 90 years. Known causes and risk factors include age, hypertension, branch atheromatous disease, cerebral amyloid angiopathy, radiation exposure, immune-mediated vasculitides, certain infections, and several genetic diseases. CSVD can be asymptomatic; however, depending on location, lesions can cause mild cognitive dysfunction, dementia, mood disorders, motor and gait dysfunction, and urinary incontinence. CSVD is diagnosed on the basis of brain imaging biomarkers, including recent small subcortical infarcts, white matter hyperintensities, lacunes, cerebral microbleeds, enlarged perivascular spaces, and cerebral atrophy. Advanced imaging modalities can detect signs of disease even earlier than current standard imaging techniques. Diffusion tensor imaging can identify altered white matter connectivity, and blood oxygenation level-dependent imaging can identify decreased vascular reactivity. Pathogenesis is thought to begin with an etiologically specific insult, with or without genetic predisposition, which results in dysfunction of the neurovascular unit. Uncertainties regarding pathogenesis have delayed development of effective treatment. The most widely accepted approach to treatment is to intensively control well-established vascular risk factors, of which hypertension is the most important. With better understanding of pathogenesis, specific therapies may emerge. Early identification of pathologic characteristics with advanced imaging provides an opportunity to forestall progression before emergence of symptoms.

Introduction: Cilostazol has promise as an alternative to aspirin for secondary stroke prevention given its vasodilatory and anti-inflammatory properties in addition to platelet aggregation inhibition. We conducted a systematic review and meta-analysis to estimate the comparative effectiveness and safety of cilostazol compared to aspirin for stroke prevention in patients with previous stroke or TIA. Hypothesis: Cilostazol is more effective than aspirin in preventing recurrent ischemic stroke with lower risk of intracranial hemorrhage and bleeding. Methods: We searched PubMed and the Cochrane Central Register of Controlled Trials from inception to 2019. Randomized clinical trials that compared cilostazol vs aspirin and reported the endpoints of ischemic stroke, intracranial hemorrhage and bleeding were included. A random-effects estimate was computed based on Mantel-Haenszel methods. The pooled estimates with 95% confidence intervals were compared between cilostazol and aspirin and displayed as forest plots (Figure). Results: The search identified 5 randomized clinical trials comparing cilostazol vs aspirin for secondary stroke prevention that enrolled 7,240 patients from primarily Asian countries (3,615 received cilostazol and 3,625 received aspirin). The pooled results from the random-effects model showed that cilostazol was associated with significantly lower risk of recurrent ischemic stroke (Hazard ratio [HR] 0.70; 95%CI, 0.54-0.89), intracranial hemorrhage (HR 0.41; 95%CI, 0.25-0.65) and bleeding (HR 0.71; 95%CI, 0.55-0.91). See forest plots. Conclusion: This meta-analysis suggests cilostazol is more effective than aspirin in the prevention of recurrent ischemic stroke with lower risk of intracranial hemorrhage and bleeding. Confirmatory randomized trials of cilostazol for secondary stroke prevention to be performed in more generalizable populations are needed.

Introduction: Left atrial enlargement (LAE) is associated with atrial fibrillation, a frequent cause of large vessel occlusion (LVO) leading to ischemic stroke. Leptomeningeal collaterals protect tissue from ischemia, but the association between collaterals and structural heart disease is not well described. We aim to investigate the association between LAE and cerebral collaterals during acute LVO when microvasculature, vasodilation, and chronotropic competence are critically important. Hypothesis: Left atrial enlargement is associated with poor collaterals. Methods: We reviewed consecutive patients presenting with middle cerebral and internal carotid LVO who underwent thrombectomy from 2012 to 2017. Patients with CT angiogram of the head and echocardiogram were included. Poor collaterals were defined as ≤ 50% filling on CT angiogram. LAE was defined as left atrial volume index ≥ 35 mL/m 2 . Multivariate logistic regression analysis was performed to evaluate the relationship between LAE and poor collaterals with adjustment for age and hypertension. Results: There were 128 eligible patients. The mean age was 68± 15 years, median NIHSS was 17, and 51 (39.8%) had LAE. Baseline characteristics are described in the table. Poor collaterals were observed in 50 (39%) patients. Patients with LAE were more likely to have poor collaterals compared to those with normal left atrial size (52.9% vs. 29.9%, p=0.009). After adjusting for age and hypertension, a trend towards association remained (OR 2.00, p=0.089). Conclusion: Our results indicate that patients with LVO and LAE were more likely to have poor collaterals. Further research is warranted to determine the cause of the association. One possibility is shared pathophysiology affecting both cardiac and cerebral vasculature such as microvascular disease or endothelial dysfunction. Alternatively, structural heart disease causing chronotropic incompetence may lead to poor collateral filling.

Introduction We assessed patients’ perceptions of physician empathy during telemedicine consultations as compared to in-person consultations during clinical encounters for acute stroke. Methods This prospective cohort study was undertaken at a comprehensive stroke centre hub in collaboration with a distant community hospital spoke site. Eligible participants presented to hub or spoke emergency departments with suspected acute stroke within three hours of symptom onset. Participants were evaluated at the hub site in person or at the remote site via telemedicine by the same group of neurologists. Following acute care decisions, single-visit data including participant-reported assessments of physician empathy were collected within 24 h. The primary outcome was the Consultation and Relational Empathy score. The secondary outcome for the telemedicine cohort was the Telemedicine Patient Satisfaction Measure score. Results Between 31 May 2013–13 March 2019, 70 patients completed the study. Fifty patients were seen by telemedicine and 20 patients were seen in person. Median Consultation and Relational Empathy scores (with a possible score of 10–50) were 49 (range 27–50) for telemedicine and 45 (range 26–50) for in-person consultations (Wilcoxon rank sum p = 0.18). Each item of the Consultation and Relational Empathy questionnaire was rated very good or excellent by at least 87% of participants in the telemedicine group. The median Telemedicine Patient Satisfaction Measure score was 54 (range 12–60), with each item rated agree or strongly agree by at least 84% of participants. Discussion We found no difference between telemedicine and in-person visits in patient perception of physician empathy in acute stroke care. Therefore, we conclude that empathy can be conveyed by facial expression, voice and attentiveness in a telemedicine encounter and, in the setting of acute stroke care, does not require physical touch or proximity.

The cholinergic heat-labile neurotoxin produced by Clostridium species is primarily responsible for the clinical manifestations of botulism. The classic phenotypic presentation of botulism consists of subacute descending flaccid paralysis with intact sensory function. Traditionally, it is classified into 3 main forms (foodborne, wound-related, and infantile) on the basis of primary site of toxin entry into the human nervous system. Toxemia is the common pathophysiology in all forms of botulism. Adult intestinal toxemia botulism is an extremely rare form of the disease with pathogenesis similar to that of infant-type botulism. Symptomatic adults usually have an anatomic abnormality in the gastrointestinal tract leading to changes in normal gut flora. The current case is an addition to the growing literature on this unusual clinical variant of botulism.

Granulomatous angiitis of the central nervous system (GACNS) is a rare cerebrovascular disorder. It usually presents with multifocal neurologic symptoms symptoms including stroke, encephalopathy, and headache. A limited number of case reports describe neurological deficits resulting from GACNS as the manifesting symptoms of Hodgkin's lymphoma (HL). We describe the case of a patient with neurological symptoms from GACNS that led to the diagnosis of HL, as well as a literature review focusing on the association between GACNS and HL.

Bulbar onset amyotrophic lateral sclerosis (bALS) is a currently incurable neurodegenerative condition characterized by insidious progression of bulbar muscle paresis; namely dyspnea, dysarthria, and dysphagia. The diagnosis of bALS requires exclusion of mimicking pathologies as the diagnosis of bALS may have significant implications on patients' quality of life, future planning, and familial/social dynamics. Herein we present two cases which were misdiagnosed as bALS when in fact a structural lesion of the hypoglossal nerve was causative. This article may serve as a reminder to entertain alternative diagnoses prior to arriving at a diagnosis of bALS., Highlights • Bulbar onset ALS may mimic a variety of potentially treatable conditions. • Tongue fasciculations may occur at any level from the hypoglossal nucleus or axon, or the lingual muscles themselves. • Accompanying neurological signs should aid in guiding diagnosis.

Asymmetric brain edema is a rare neurologic complication after cardiovascular surgery. We describe the clinical and imaging features of an asymmetric brain edema syndrome in a 52-year-old man following cardiac transplantation who presented with facial myoclonus and left hemiparesis in the postoperative period. To our knowledge, this is the first case report of asymmetric brain edema syndrome after cardiac transplant and the second following cardiac surgery. Arterial bypass cannula malposition in the ascending aorta or brachiocephalic artery with subsequent cerebral hypoperfusion and subsequent hyperperfusion appears to be the most likely physiologic cause.

A 69-year-old man was admitted to our hospital with left upper quadrant pain, splenomegaly, acute renal failure, hyperuricemia, thrombocytopenia (platelet count 32,000/mm3), and leukocytosis (leukocyte count 88,000/mm3). His medical history was significant for prior diagnosis of myelodysplastic syndrome (MDS) by bone marrow biopsy at an outside institution treated with the hypomethylating chemotherapeutic agent decitabine, atrial fibrillation, cardiomyopathy, and complete pacemaker dependence. Neurologic examination upon admission was normal. The initial diagnostic considerations were tumor lysis syndrome from decitabine treatment vs transformation of MDS to acute myeloid leukemia (AML).

Limb-shaking transient ischemic attacks (LSTIAs) are a phenomenon that occurs due to transient hypoperfusion to a cerebral motor territory with a chronically outstripped autoregulatory vascular reserve. First described in 1962 by Miller Fisher, the pathogenesis and the global understanding of this presentation have undergone a significant advancement throughout the years. Typically, patients will present with this syndrome of transient hypoperfusion in the context of extracranial carotid intrinsic vessel stenosis or by intracranial vascular stenosis to select motor pathways. We present within this case report a novel mechanism by which LSTIAs may emerge. Through this knowledge, clinicians may need to consider expansion of their diagnostic breadth to include proximal vasculature luminal integrity.

Balint syndrome (simultagnosia, optic ataxia, and ocular apraxia) is typically caused by pathology affecting the parietal-occipital regions bilaterally. Visual allochiria is an uncommonly reported symptom associated with parietal lobe pathology in which visual stimuli presented to one hemispace are transposed to the opposite side. We describe a patient with Balint syndrome and visual allochiria whose initial brain MRI demonstrated acute infarction of the right parietal-occipital region. Repeat imaging 9 days later revealed bilateral parietal-occipital infarctions consistent with the observed clinical syndrome. Reversible cerebral vasoconstriction syndrome is introduced as a novel cerebrovascular etiology of Balint syndrome.

Živkovic SA, Eidelman BH, Bond G, Costa G, Abu-Elmagd KM. The clinical spectrum of neurologic disorders after intestinal and multivisceral transplantation. Clin Transplant 2009: DOI: 10.1111/j.1399-0012.2009.01065.x © 2009 John Wiley & Sons A/S. Abstract: Background: Intestinal transplantation has evolved into an effective therapy for patients with intestinal failure and the inability to be maintained on total parenteral nutrition. Long-term heavy immunosuppression and complex systemic disturbances increase the risk of the neurologic complications. Methods: This retrospective analysis identified the post-transplant neurologic complications in adult patients who underwent intestinal transplantation at the University of Pittsburgh Medical Center between May 1990 and August 1998. The recipients received 28 isolated intestine, 17 composite liver-intestine, and nine multivisceral allografts. Results: With a median follow-up of 25 months, 46 of 54 recipients (68%) developed headaches (n = 27; 50%), encephalopathy (n = 23; 43%), seizures (n = 9; 17%), neuromuscular disorders (n = 4; 7%), opportunistic CNS infections (n = 4; 7%), and ischemic stroke (n = 2; 4%). Conclusions: Under high maintenance immunosuppression, intestinal transplant recipients were at high risk for neurologic complications. Future studies are needed to describe post-transplant neurologic complications with modern immunosuppression protocols.

Tacrolimus (FK506) has recently been approved for immunosuppression in organ transplantation, although its use is accompanied by a wide spectrum of neurotoxic side effects. We describe the clinical, radiological, and pathological features of 3 cases of tacrolimus-related leukoencephalopathy. The syndrome of immunosuppression-related leukoencephalopathy is proposed as an uncommon neurological syndrome occurring in patients with organ transplants involving demyelination, in particular in the parieto-occipital region and centrum semiovale. Although the syndrome is not associated with a particular (absolute) serum level of tacrolimus, it resolves spontaneously upon decreasing the dose. The tacrolimus-related syndrome has a similar radiographic and pathologic appearance as the analogous syndrome that occurs in patients taking cyclosporine.

Numerous mechanical cardiac support devices have been developed during the past 10 years for use in various applications, ranging from total artificial hearts to single ventricular support devices. Ventricular assist devices promise to play an important role in providing circulatory support in patients awaiting cardiac transplantation. The most significant complications associated with artificial hearts relate to thromboembolism. This article reviews a variety of mechanical support devices, focusing on thromboembolic complications and their pathophysiologic mechanisms.

Chronic cough is defined as a daily cough lasting for more than eight weeks. We report an unusual case of chronic cough as the primary manifestation of obstructive hydrocephalus. Chronic cough in our case was determined to be of neurogenic origin only after exhaustive investigations failed to reveal a systemic cause, and, in particular, after a positive response to treatment of the hydrocephalus was observed. To the best of our knowledge, this is the first report of hydrocephalus presenting as chronic cough. We believe this case will remind physicians of the importance of considering neurological disease as a cause of chronic cough after common causes are excluded.

Intestinal transplantation has evolved into an effective therapy for patients with intestinal failure and the inability to be maintained on total parenteral nutrition. Long-term heavy immunosuppression and complex systemic disturbances increase the risk of the neurologic complications.This retrospective analysis identified the post-transplant neurologic complications in adult patients who underwent intestinal transplantation at the University of Pittsburgh Medical Center between May 1990 and August 1998. The recipients received 28 isolated intestine, 17 composite liver-intestine, and nine multivisceral allografts.With a median follow-up of 25 months, 46 of 54 recipients (68%) developed headaches (n = 27; 50%), encephalopathy (n = 23; 43%), seizures (n = 9; 17%), neuromuscular disorders (n = 4; 7%), opportunistic CNS infections (n = 4; 7%), and ischemic stroke (n = 2; 4%).Under high maintenance immunosuppression, intestinal transplant recipients were at high risk for neurologic complications. Future studies are needed to describe post-transplant neurologic complications with modern immunosuppression protocols.

We measured anorectal sensory and motor function in 11 patients with multiple sclerosis and fecal incontinence, 11 continent patients with multiple sclerosis, 10 diabetics with fecal incontinence, and 12 healthy control subjects. The threshold volume at which patients with multiple sclerosis and fecal incontinence experienced rectal sensation was higher than that in healthy controls (42.7 +/- 6.2 mL vs. 13.3 +/- 2.8 mL; P less than 0.01) and was similar to that in incontinent diabetics (36.5 +/- 5.7 mL). Patients with multiple sclerosis and incontinent diabetics also showed increased thresholds of phasic external sphincter contraction compared with controls (P less than 0.05). Diabetics with incontinence had reduced resting and maximal voluntary anal sphincter pressures compared with controls (P less than 0.05), whereas patients with multiple sclerosis and incontinence showed only decreased maximal voluntary anal sphincter pressures (P less than 0.01 vs. controls and diabetics). Incontinent patients with multiple sclerosis also required smaller volumes of rectal distention to inhibit internal sphincter tone compared with diabetics and controls (P less than 0.01). Decreased maximal voluntary squeeze pressures were less severe in continent patients with multiple sclerosis than in incontinent patients with multiple sclerosis. We conclude that impaired function of the external anal sphincter and decreased volumes of rectal distention to inhibit the internal anal sphincter or both may contribute to fecal incontinence in multiple sclerosis. In addition, increased thresholds of conscious rectal sensation in some incontinent patients with multiple sclerosis and diabetes mellitus may contribute to fecal incontinence by impairing the recognition of impending defecation.

A 79-year-old woman with a history of prior right frontal infarction presented with sudden inability to speak (figure, A). Examination revealed anarthria, yet intact comprehension, writing, and limb function (video). Voluntary …

An unselected outpatient population of 280 individuals with multiple sclerosis was surveyed to determine the prevalence of bowel dysfunction and to define their characteristics and their relationship to the nongastrointestinal manifestations of the disease. Constipation was present in 43%, was similar in frequency in both sexes, and was more common in patients, regardless of degree of disability, than in a control population. Frequency of constipation also correlated with duration of disease and genitourinary symptoms but did not correlate with use of any medications in mildly disabled patients. Fecal incontinence had occurred at least once in the preceding 3 mo in 51% of patients and once per week or more frequently in 25% of patients who were questioned in more detail with a follow-up questionnaire. Correlations of fecal incontinence with disability, duration of disease, and presence of genitourinary symptoms were similar to constipation. The prevalence of bowel dysfunction (constipation and/or fecal incontinence) in the multiple sclerosis population was 68%, and this manifestation was common even in mildly disabled subjects. Bowel dysfunction can be a source of considerable ongoing social disability in patients with multiple sclerosis. Further studies are needed to characterize the pathophysiology of this common disorder so that effective therapeutic strategies can be identified.

We describe a patient who presented with a 1-h history of vertical diplopia and nystagmus and was found to have acute left ventrolateral thalamic infarction on the diffusion-weighted magnetic resonance imaging (DWI MRI). This is the first case report demonstrating that vertical diplopia and nystagmus, which typically suggest a lesion in the brainstem or cerebellum, may also occur in acute thalamic infarction. DWI MRI can detect thalamic infarction as early as 1 h after its clinical manifestations.

A 42-year-old man had fever, chills, and bilateral visual loss. Visual acuity was markedly subnormal OU and ophthalmoscopy disclosed optic disc swelling with retinal thickening extending into the macula OU, findings consistent with neuroretinitis. Fluorescein angiography revealed optic disc leakage and submacular accumulation of dye OU without retinal vascular leakage. Optical coherence tomography (OCT) showed outer plexiform layer retinal edema and subfoveal detachments. There was evidence of active human immune deficiency virus and cytomegalovirus infections. Several weeks after multidrug therapy, sequential OCT scans documented resolution of the outer plexiform edema and submacular detachments in parallel with improved visual acuity. The OCT findings support the theory that submacular detachments in neuroretinitis result from diffusion of fluid from the optic disc to the outer plexiform layer and through the outer limiting membrane to the subretinal space.

The majority of immunosuppressive agents used to prevent rejection in organ transplant recipients are neurotoxic and can impact upon the function of structures throughout the nervous system. The clinical manifestations can be quite diverse.

Purpose Diagnosing brain death is important in managing the comatose patient for whom the continuation of life support is being questioned and when organ harvesting is being considered. The virtual immediate localization of Tc-99m HMPAO to cerebral and cerebellar tissue provides an index of blood perfusion, and its absence denotes brain death. Other methods for assessing brain death include cerebral angiography, MRI, CT imaging after inhalation of stable xenon, electroencephalography, and clinical examination. The contrast material used for angiography may damage harvested organs, and the other studies have significant errors. MRI, CT imaging, and angiography are unsuitable for bedside use. Methods Twenty-three patients, who presented with head trauma, prolonged anoxia or intrinsic brain disease (e.g., glioblastoma multiforme) and who were brain-dead by clinical examination criteria, were referred to the nuclear medicine division for verification of brain death. For adults, approximately 25 mCi Tc-99m hexamethylpropylene amineoxime (HMPAO) was administered intravenously. All patients but one were imaged using a mobile scintillation camera at the bedside. Results We demonstrated (1) both cerebral and cerebellar perfusion, (2) neither cerebral nor cerebellar perfusion, (3) cerebral without cerebellar perfusion, and (4) cerebellar without cerebral perfusion. Patients without cerebral perfusion were diagnosed as brain-dead. The significance of a viable cerebellum in the absence of cerebral viability was not fully appreciated, although organs were harvested from such patients. We determined how well the clinical examination criteria held up in the diagnosis of brain death against the new gold standard of Tc-99m HMPAO scintigraphy: Clinical examination criteria correctly predicted brain death only 83% of the time compared with HMPAO scintigraphy. Conclusions Brain death assessment by Tc-99m HM-PAO scintigraphy has proved to be a reliable, safe, and cost-effective bedside method and may have practical application in the assessment of brain death in potential cadaveric donors.

Sirolimus is widely used as a primary immunosuppressive agent, but there have been no clinical reports of neurotoxicity.1 However, laboratory evidence suggests that sirolimus is potentially neurotoxic, as it has been shown to alter metabolism in astrocytes with resultant structural changes.2 We present a case of sirolimus-induced posterior reversible encephalopathy syndrome (PRES) with a lobar intracranial hemorrhage. A 51-year-old woman was the recipient of a single lung transplant 2 years prior to presentation. The procedure was indicated for progressive pulmonary failure secondary to emphysema. The post-transplantation course was complicated by hypertension (HTN) and left kidney malignancy. Blood pressure was subsequently adequately controlled on medication, and the tumor entirely eradicated by cryoablation. The neurologic presentation was characterized by right occipital pain radiating anteriorly with accompanying deterioration in vision. She was unable to fuse images, but denied frank diplopia. Medications included lopressor, clonidine, losartan, hydralazine, sirolimus, prednisone, famotidine, fentanyl …

We have taken the opportunity of a clinical trial of the potential efficacy and safety of FK 506 (tacrolimus) in chronic progressive multiple sclerosis (MS) to examine the influence of this potent new immunosuppressant on circulating T-lymphocytes in an otherwise healthy non-transplant population. Peripheral blood levels of subsets of CD4+ T lymphocytes expressing the activation molecule interleukin-2 receptor (p55 alpha chain; CD25) or the CD45RA isoform were determined sequentially in 19 patients that were treated continuously with oral FK 506 (starting dose 0.15 mg/kg/day) for 12 months. No significant change in the proportion of circulating CD25+ CD4+ cells was observed over the study period in which the mean trough plasma FK 506 level rose from 0.3 +/- 0.2 to 0.5 +/- 0.4 ng/ml. There was also no significant effect of FK 506 on the percentage of CD45R+ CD4+ cells in the peripheral blood at 12 months compared with pretreatment values. Analysis of a subgroup of 7 patients, who showed a sustained reduction in CD25+ CD4+ cells and a reciprocal increase in CD45RA+ CD4+ cells for at least 6 months after start of treatment, did not reveal any difference in disability at one year compared with the treatment group as a whole. The side effects of FK 506 were mild and the overall degree of disability estimated by the mean Kurtzke expanded disability status scale (EDSS) score or the ambulation index did not deteriorate significantly in the 19 patients studied over the 12 months of FK 506 administration.

This study evaluated whether improvement of headaches during relaxation therapy was related to pretreatment scores on tests measuring depression: the Beck Depression Inventory (BDI) and the depression scale of the MMPI. Seventeen patients were treated in eight 1-hour sessions of relaxation therapy. During treatment, there was a significant improvement of headache activity averaging a 34% decrease in pain with 24% much improved, 41% moderately improved, and 35% inimproved. Multiple regression analyses indicated that, controlling for differences in pretreatment pain levels, there were significant negative correlations between improvement and scores on the Beck, but not for scale 2 of the MMPI. For the BDI, a score of 8 or above predicted poor prognosis and a score of 3 or less predicted favorable prognosis.

Infusion of 5-hydroxytryptamine (5HT) into the internal carotid artery of normal baboons was not accompanied by alteration of gray matter cerebral blood flow. In animals pretreated with depot estrogen and progesterone (dosage equivalent to oral contraceptive preparations), infusion of 5HT produced a marked decrease in gray matter blood flow. A similar decrease in flow was obtained when the 5HT was infused with a concentrate of beta-lipoprotein. Steroid substances appear to enhance the cerebrovascular constrictor responses to 5HT. A further series of six experiments has shown that the monoamine oxidase inhibitor tranylcypromine similarly produced constrictor responses to 5HT. It is possible that the steroids, the beta-lipoprotein, and the tranylcypromine produced constrictor responses to 5HT by the same mechanism (inhibition of cerebrovascular monoamine oxidase).

Cerebral blood flow was measured in 17 baboons before and during infusion of 5-hydroxytryptamine (5-HT) into the internal carotid artery. The mean values for total cerebral blood flow, grey matter flow, and white matter flow before 5-HT infusion were 40.8, 59.2, and 12.7 ml/min/100 gm of tissue, respectively. There was no significant alteration in total blood flow or flow through grey matter when 5-HT was infused at dosages ranging from 0.5 to 10.0 microng/kg/min. A small but significant decrease in white matter blood flow was recorded when 5-HT was infused at a rate exceeding 2.5 microng/kg/min. The study indicates that in vivo, with the xenon clearance method, intra-arterial infusion of 5-HT does not significantly alter cerebral blood flow.

Cerebral blood flow responses to intra-arterial infusion of norepinephrine (NE) at 0.55 microgram/kg/min and 1.1 microgram/kg/min were studied in 3 groups of baboons. The flow was measured by the intracarotid 133xenon clearance technique using a computer program to calculate flow (height over area--H/A) flow (initial slope--is) and cerebral metabolic utilization of oxygen (CMRO2). The normal response to NE was to increase flow without significant changes in CMRO2. Blockade of catechol-o-methyl transferase (COMT) produced vasoconstrictor responses to these same NE doses. Monoamine oxidase blockade abolished the normal vasodilation. Denervation of the cerebral circulation with intracisternal 6-hydroxydopamine produced vasoconstrictor responses with flow (H/A) but not with flow (is). It is concluded that the extra-neuronal COMT enzyme is important in limiting the access of blood-borne NE to cerebrovascular constrictor receptors.

We hypothesized that when the depth of ether anesthesia is increased from 2 to 5%, cerebral vessels dilate secondary to circulating catecholamine stimulation of cerebral metabolism. Cerebral blood flow (CBF) by 133Xe clearance and cerebral metabolic rate for oxygen (CMRO2) were measured on 2% and then 5% ether in air in two groups of seven monkeys each during mechanical ventilation. Propranolol, 0.5 mg/kg i. v., was infused over 5 min in one group, and the other received saline. All measurements were repeated on 5% and 2% ether. Cerebrovascular resistance (CVR) fell by 30%, from 2.28 2± 0.61 (mean ± SD) to 1.51± 0.28 mm Hg ml−1 100 g−1 min−1 (p < 0.01), with the increase in ether from 2 to 5%. CBF and CMRO2 were unaltered from values of about 45 ml 100 g−1 min−1 and 2.3 ml 100 g−1 min−1, respectively. During 5% ether anesthesia, propranolol had no effect on CBF, CMRO2, or CVR. On 2% ether, it increased CVR twofold, from 1.5 ± 0.30 to 3.0 ± 1.0 mm Hg ml−1 100 g−1 min−1, and decreased CBF by 33%, from 48 ± 8 to 32 ± 10 ml 100 g−1 min−1. Plasma epinephrine was twofold higher on 2% compared to 5% ether, both before and after saline or propranolol infusion. In monkeys, cerebrovascular dilation by ether at 5% compared to 2% is not secondary to catecholamine stimulation of CMRO2. It may result from a direct effect of either plasma catecholamines or ether on the cerebrovasculature.

Sensory neuropathies, particularly trigeminal neuropathy, have been recognized as neurological complications of Sjogren's syndrome, but the pathogenesis has not been established. We describe a woman with primary Sjogren's syndrome who developed a progressive debilitating subacute sensory neuronopathy. Results of electrophysiological studies were consistent with involvement of the trigeminal and dorsal root ganglia. A thoracic dorsal root ganglion biopsy showed lymphocytic infiltration and degeneration of ganglion cells. We believe that this is the first description of biopsy-documented dorsal root ganglionitis in a subacute sensory neuronopathy associated with Sjogren's syndrome and that the finding suggests an immunopathogenic basis.

The effect of intracarotid infusion of 5-hydroxytryptamine (5-HT) on cerebral blood flow was studied in five female baboons 7 days after intramuscular injection of slow release estrogen and progesterone. The control values for total cerebral blood flow, grey matter flow, and white matter flow were 38.9, 57.5, and 11.0 ml/min/100 gm of tissue respectively. There was a statistically significant decrease in total, grey and white matter blood flow during infusion of 5-HT at dosages ranging from 0.5 to 10.0 microng/kg/min. The study indicates that in female baboons pretreated with estrogen and progesterone, intracarotid infusion of 5-HT produces a dose dependent decrease in cerebral blood flow, which did not occur in control animals.

Hemifacial spasm is usually an isolated symptom resulting from facial nerve root compression. Three patients had, in addition, tinnitus, hearing loss, facial sensory loss, diminished gag reflex, dysphagia, and dysarthria. Acoustic reflexes were abnormal, and facial nerve conduction studies showed evidence of ephaptic transmission and ectopic excitation. Brain CT and metrizamide cisternography were normal. Surgical exploration showed compression of cranial nerve roots by posterior inferior cerebellar artery branches. After decompression, symptoms abated, and electrical signs of hemifacial spasm disappeared. Vascular compression of nerve roots in the cerebellopontine recess may cause multiple cranial neuropathy.

Cerebral blood flow (CBF) was measured in 20 baboons by the intra-arterial xenon-133 injection method. The CBF responses to intra-arterial infusions of noradrenaline (NA) were determined. These responses were normally found to be vasodilator and mediated by beta adrenoreceptors. After infusion of substances blocking extraneuronal uptake of NA or opening of the blood-brain barrier, this vasodilation was either abolished or converted to an alpha-receptor mediated vasoconstriction. This suggests that normally the cerebral circulation is protected against noradrenergic vasoconstriction by mechanisms reducing the concentration of NA in the tunica media to below threshold for alpha-adrenoreceptor stimulation.

SYNOPSIS Sixty percent of female headache sufferers have an increase paramenstrually. Although behavioraltreatment of migraine and tension headache has proven effective in controlled studies, the effect onparamenstrual increases has rarely been isolated and observed. The purpose of this study was todemonstrate the effects of two types of nonpharmacological treatment on menstrual headache: 1)relaxation with EMG and thermal biofeedback, and 2) person-centered insight therapy, as an alternativetreatment control. The design was that of the time series method. Diagnosis was made into subtypes ofmigraine, muscle-contraction, mixed and cluster headache. 16 women with paramenstrual headaches selfmonitored 4 times daily for a 2-cycle baseline, then were matched on pre-treatment pain levels into 8 pairsand randomly assigned to treatment, 12 sessions carried out over 3 cycles, with a one-month follow-upcycle. Post-treatment group data analysis was by three-way analysis of variance with 2 repeatedmeasures. There were no significant main effects of group or time, although individual clinical analysis bypercent improvement demonstrated a trend of greater improvement in the behavioral group. Resultssuggest that nonpharmacological treatment has a lesser impact on menstrually associated headachesthan on headaches not associated with menstruation.

We report two women with ocular flutter and saccadic intrusions, documented by electro-oculography, who had complete spontaneous remission of their ocular motor findings prior to the appearance of a primary neoplastic process remote from the nervous system. Transient elevation of blood HVA and VMA levels was detected in one patient who subsequently had breast cancer. These cases indicate that spontaneous remission of saccadic oscillations does not necessarily imply a benign outcome. Patients with this ocular motor abnormality should be followed closely for signs of a remote neoplasm even if initial investigation is negative.

Despite many studies, the cerebrovascular action of infused noradrenalin is still unclear. The study reported here tested the hypothesis that infused noradrenalin is prevented from reaching the adrenoreceptors by being avidly taken up and metabolized in the vascular smooth muscle. Cerebral blood flow was measured by the xenon133 clearance technique in nine baboons before and during blockade of the enzyme catechol-O-methyl transferase, which is known to be important in inactivation of circulating noradrenalin. The cerebral blood flow responses to noradrenalin infused at 8, 16, and 32 mug per minute were also determined. Responses indicated vasodilatation before but vasoconstriction after blockade, with a significant noradrenalin. It is suggested that the cerebral circulation is normally protected against sympathetic vasoconstriction by the avid uptake and metabolism of noradrenalin in extraneuronal and possibly neuronal sites.