Markus Beitzke

Clinical Presentation, Etiology, and Long-Term Prognosis in Patients With Nontraumatic Convexal Subarachnoid Hemorrhage

Background and Purpose— Nontraumatic subarachnoid hemorrhage at the convexity of the brain (cSAH) is an incompletely characterized subtype of nonaneurysmal subarachnoid bleeding. This study sought to systematically describe the clinical presentation, etiology, and long-term outcome in patients with cSAH. Methods— For a 6-year period, we searched our radiological database for patients with nontraumatic nonaneurysmal subarachnoid hemorrhages (n=131) seen on CT or MRI. By subsequent image review, we identified 24 patients with cSAH defined by intrasulcal bleeding restricted to the hemispheric convexities. We reviewed their medical records, analyzed the neuroimaging studies, and followed up patients by telephone or a clinical visit. Results— The 24 patients with cSAH had a mean age of 70 years (range, 37–88 years), 20 (83%) were >60 years, and 13 (54%) were women. Patients often presented with transient sensory and/or motor symptoms (n=10 [42%]) and seizures (n=5 [21%]), whereas headaches typical of subarachnoid hemorrhage were rare (n=4 [17%]). MRI provided evidence for prior bleedings in 11 patients (microbleeds in 10 and parenchymal bleeds in 5) with a bleeding pattern suggestive of cerebral amyloid angiopathy in 5 subjects. At follow-up (after a mean of 33 months), 14 patients (64%) had an unfavorable outcome (modified Rankin scale score 3–6), including 5 deaths. We did not observe recurrent cSAH. Conclusions— Our data suggest that cSAH often presents with features not typical for subarachnoid bleeding. In the elderly, cSAH is frequently associated with bleeding-prone conditions such as cerebral amyloid angiopathy. Recurrence of cSAH is rare but the condition itself is a marker of poor prognosis.

Autonomic dysfunction and hemodynamics in vitamin B12 deficiency

Orthostatic hypotension in patients with cobalamin (Cbl) deficiency has been reported previously in isolated cases but we are not aware of detailed systematic studies of hemodynamic and autonomic nervous system function in patients with cobalamin deficiency. We investigated hemodynamic and autonomic responses to 60 degrees passive head up tilt (HUT) in 21 patients with vitamin B12 deficiency, 21 healthy age-matched control subjects and 9 age-matched patients with diabetes mellitus (DM) and established diabetic neuropathy. To systematically assess hemodynamic and autonomic nervous system function, we performed measurements of heart rate, beat-to-beat systolic and diastolic blood pressure, stroke index, cardiac index, total peripheral resistance index, total power, low (LF) and high (HF) frequency oscillatory component of heart rate variability, LF/HF ratio and spontaneous baroreflex sensitivity. As compared to controls, we found a significant fall of systolic blood pressure during 60 consecutive beats directly after head up tilt; furthermore, a significantly blunted fall of stroke index, cardiac index and a lack of increase of total peripheral resistance index for the duration of tilt in patients with diabetes mellitus and in patients with vitamin B12 deficiency. As compared to controls, we observed an altered response of spectral indices of sympathetic activation and vagal withdrawal and an impaired modulation of baroreflex sensitivity during head up tilt suggestive of a complex modification in the neural control activities in patients with cobalamin deficiency, which was comparable to that observed in patients with diabetes mellitus and established autonomic neuropathy. The results suggest that vitamin B12 deficiency causes autonomic dysfunction with similar hemodynamic consequences and patterns of autonomic failure as seen in diabetic autonomic neuropathy. Defective sympathetic activation may be the cause for orthostatic hypotension, which is occasionally seen in patients with vitamin B12 deficiency. It is concluded that patients with orthostatic hypotension should be screened for cobalamin deficiency.

Sex-Related Differences of Acute Stroke Unit Care: Results From the Austrian Stroke Unit Registry

Background and Purpose— Sex-related differences in quality of acute stroke care are an important concern with limited data available, specifically regarding stroke unit (SU) setting. We used the prospective nationwide Austrian SU registry to address this issue. Methods— Our analysis covered an 8-year time period (January 2005 to December 2012) during which all patients with transient ischemic attack or ischemic stroke admitted to 1 of 35 Austrian SU had been captured in the registry. These data were analyzed for age-adjusted preclinical and clinical characteristics and quality of acute stroke care in men and women. In addition, we assessed the outcome at 3 months in multivariate analysis. Results— A total of 47 209 individuals (47% women) had received SU care. Women were significantly older (median age: 77.9 versus 70.3 years), had higher pre-existing disability and more severe strokes. Correcting for age, no significant sex-related differences in quality of care were identified with comparable onset-to-door times, times to and rates of neuroimaging, as well as door-to-needle times and rates of intravenous thrombolysis (14.5% for both sexes). Despite equal acute stroke care and a comparable rate of neurorehabilitation, women had a worse functional outcome at 3-month follow-up (modified Rankin scale 3–5: odds ratio, 1.26; 95% confidence interval [1.17–1.36]), but a lower mortality (odds ratio, 0.70; 95% confidence interval [0.78–0.88]) after correcting for confounders. Conclusions— We identified no disproportions in quality of care in the acute SU setting between men and women, but the outcome was significantly different. Further studies on the poststroke period including socioeconomic aspects are needed to clarify this finding.

Contribution of Convexal Subarachnoid Hemorrhage to Disease Progression in Cerebral Amyloid Angiopathy

Background and Purpose— Cerebral amyloid angiopathy–related cortical superficial siderosis (cSS) seems to indicate an increased risk of subsequent intracerebral hemorrhage (ICH). We wanted to identify the mechanisms and sequence of hemorrhagic events which are responsible for this association. Methods— During a 9-year-period, we identified patients with spontaneous convexal subarachnoid hemorrhage (cSAH) and performed a careful longitudinal analysis of clinical and neuroimaging data. A close imaging–histopathologic correlation was performed in one patient. Results— Of 38 cSAH patients (mean age, 77±11 years), 29 (76%) had imaging features of cerebral amyloid angiopathy on baseline magnetic resonance imaging. Twenty-six (68%) had cSS. Sixteen subjects underwent postcontrast magnetic resonance imaging. Extravasation of gadolinium at the site of the acute cSAH was seen on all postcontrast scans. After a mean of 24±22 (range 1–78) months of follow-up, 15 (39%) had experienced recurrent cSAHs and 14 (37%) had suffered lobar ICHs. Of 22 new ICHs, 17 occurred at sites of previous cSAHs or cSS. Repeated neuroimaging showed expansion of cSAH into the brain parenchyma and evolution of a lobar ICH in 4 patients. Propagation of cSS was observed in 21 (55%) patients, with 14 of those having experienced recurrent cSAHs. In the autopsy case, leakage of meningeal vessels affected by cerebral amyloid angiopathy was noted. Conclusions— In cerebral amyloid angiopathy, leakage of meningeal vessels seems to be a major cause for recurrent intrasulcal bleedings, which lead to the propagation of cSS and indicate sites with increased vulnerability for future ICH. Intracerebral bleedings may also develop directly from or in extension of a cSAH.

Primary leptomeningeal lymphoma of the cauda equina: a rare cause of radiculopathy

Primary leptomeningeal lymphoma (PLML) is a particularly rare neoplasm, accounting for only 7% of all primary central nervous system lymphomas. PLML is defined as a syndrome of lymphomatous meningeal infiltration without identification of systemic lymphoma or parenchymal CNS lymphoma in the clinical course of the disease [6, 12]. The diagnosis is challenging and requires a high index of suspicion. Early diagnosis, however, is crucial as immediate treatment may be beneficial. We here report a case of PLML of the cauda equina to raise awareness for this disorder and reduce the delay to diagnosis in similar cases. A 69-year-old immunocompetent man complained about increasing low back pain and moderate weakness of the left leg, which had slowly developed over 1 year. Neurologic examination and electrodiagnostic studies indicated a left-sided L5–S1 radiculopathy. There was no evidence of polyneuropathy. MRI of the spine, the pelvis, and the brain, including contrast-enhanced sequences, was unremarkable. Routine lumbar puncture yielded normal findings. The patient underwent an extensive laboratory and image work-up to rule out malignant, autoimmune, or infectious disease. Due to negative findings, he was discharged to home. High-resolution, contrast-enhanced MR neurography [7, 10] and a second lumbar tap were performed 36 days later. Analysis of the cerebrospinal fluid (CSF) revealed 0 cells/ll with a normal glucose and protein content and imaging findings were again inconclusive (Fig. 1a and b). Short inversion time inversion recovery (STIR) images, however, then illustrated hyperintensity and contrast enhancement of the left piriformis muscle and the left medial gluteal muscle, suggesting acute denervation (Fig. 1c). Subsequent treatment with intravenous methylprednisolone 10 mg/kg/day for 5 days was without clinical benefit at that point. Only 9 months later, the patient was readmitted with a pronounced flaccid lower extremity paraparesis and severe low back pain. Contrast-enhanced MRI of the lumbar spine then disclosed abnormal thickening and marked linear enhancement coating multiple cauda equina nerve roots highly suggestive of leptomeningeal infiltration by tumor (Fig. 2a–c). Urgent analyses of the CSF revealed elevated protein (439 mg/dl; normal range: 15–45) and a lymphocytic pleocytosis (70 cells/ll) with many atypical cells consistent with lymphoma. A biopsy of an anterior cauda equina nerve root as highlighted by immunohistochemistry with S100 (Fig. 2d) and NSE revealed a massive diffuse interstitial infiltrate of atypical lymphocytic cells, that reached the marginal area of the small specimen with epithelial membrane antigen (EMA) positive cells indicating leptomeningeal infiltration [14]. The cells expressed CD20 and CD79, but were negative for Kl-1, EMA, CD56, M. Beitzke (&) C. Enzinger F. Fazekas Department of Neurology, Medical University of Graz, Auenbruggerplatz 22, 8036 Graz, Austria e-mail: markus.beitzke@klinikum-graz.at

Community acquired Staphylococcus aureus meningitis and cerebral abscesses in a patient with a Hyper-IgE and a Dubowitz-like syndrome

The Hyper-IgE syndrome (HIES) is a rare primary immunodeficiency which recently has been associated with heterozygous dominant-negative mutations in the signal transducer and activator of transcription 3 (STAT3). Although HIES is characterized by recurrent staphylococcal infections, the microbial invasion of the central nervous system (CNS) is definitively uncommon. We here report on Staphylococcus aureus meningitis and cerebral abscesses acquired in the community in a 31-year-old female patient with a de novo heterozygous mutation of STAT3 and a Dubowitz-like syndrome characterized by growth retardation, microcephaly and eczema. The patient presented with a relative paucity of clinical symptoms despite severe cerebrospinal fluid pathology and multiple cerebral abscesses. Antimicrobial as well as treatment with intravenous immunoglobulin was well tolerated and led to a slow recovery over a 6 months period. Our observation adds community acquired S. aureus meningitis to the list of life-threatening infections in STAT3-deficient HIES and should also raise awareness for the unusual clinical presentation of severe neuroinfection in this syndrome. Whether the association of HIES with Dubowitz-like syndrome was purely coincidental, possibly supportive of the CNS infection, or suggests a genetic overlap of these syndromes, awaits clarification.

Recurrent Hyperperfusion Syndrome and Intracerebral Hemorrhage after Recanalization of the Extracranial Carotid Artery

Thirteen months later, in November 2002, she was referred for treatment of a carotid restenosis. The patient had been asymptomatic since the first procedure. When assessed at our institution, the patient showed a residual mild, right hemiparesis. Doppl er ultrasound revealed 80% stenosis of the left ICA and common carotid artery (CCA). There was also a high-grade left external carotid artery stenosis. The vessels of the posterior circulation appeared normal. Transcranial Doppler (TCD) studies revealed reduced left middle cerebral artery (MCA) flow velocities (VL; left MCA: VL systolic 0.8 m/s, VL diastolic 0.35 m/s; right MCA: VL systolic 1.2 m/s, VL diastolic 0.4 m/s). There was no evidence of any extraintracranial collateral vascularization or cross-flow to the left ICA territory via the circle of Willis. Brain CT revealed a parenchymal defect after ICH in the left frontoparietal region. 99 Tc HMPAO-SPECT showed reduced radionuclide tracer uptake in the left ICA territory, which further decreased after acetazolamide challenge. Selective intra-arterial angiography revealed 1 80% left CCA stenosis and 1 50% left ICA stenosis according to NASCET ( fig. 1 ). The intracerebral angiogram was normal. Uneventful carotid artery stenting (CAS) was performed. On the first day after CAS, color Doppler ultrasound revealed normal VL in the region of the The term cerebral hyperperfusion syndrome (HS) was coined by Sundt et al. [1] in 1981 to describe a rare complication of carotid endarterectomy (CEA) which may appear with severe unilateral headaches, seizures and focal symptoms related to cerebral edema or intracerebral hemorrhage (ICH) and is considered to result from a major increase in ipsilateral cerebral blood flow above the metabolic demands of the brain. Obvious risk factors include long-standing hypertension, high-grade stenosis, poor collateral blood flow and contralateral carotid occlusion [2–4] . Several mechanisms such as a paralysis of cerebral autoregulatory mechanisms, a break-down of the baroreceptor-reflex and an axon-like trigeminovascular reflex have been implicated in the pathophysiology of hyperperfusion and in the evolution of the cerebral HS [2] . Once it is associated with ICH, the prognosis tends to be poor [2, 4] . We here illustrate the obvious role of endothelial damage in the development of intracerebral bleeding with the imaging findings in a rare case of a recurrent cerebral HS.

Cortical Superficial Siderosis and Risk of Bleeding after Thrombolysis for Ischemic Stroke

Background: Cortical superficial siderosis (CSS) is a neuroimaging marker of cerebral amyloid angiopathy and has been associated with a high risk for early subsequent major intracranial hemorrhage (ICH). Therefore, many experts recommend withholding of antithrombotic medication to patients with CSS. In this study, we sought to investigate the prevalence of CSS and the associated risk of ICH in the setting of intravenous thrombolysis (IVT) for ischemic stroke. Methods: We retrospectively searched the medical documentation system of our primary and tertiary care university clinic for all patients with ischemic stroke that received IVT from 2009 to December 2014. All available imaging data were reviewed in a standardized manner and blinded to any clinical data for the presence of CSS and ICH. CSS was defined as linear signal loss along the cerebral cortex on gradient echo T2*-weighted sequences. A stroke neurologist, who was blinded to the neuroimaging data, extracted the corresponding clinical data including follow-up information. Results: We identified 298 patients that received IVT and had undergone brain MRI (mean age 67.6 ± 12.6 years, 59.4% male). Cerebral MRI was performed in 116 patients (38.9%) before and in 182 patients (61.1%) after IVT (median time from stroke symptom onset to MRI: 1 day; range 0-7 days). Only 3 patients (2 females and 1 male aged 90, 76 and 73 years, respectively) had CSS (1%). All of them had a middle cerebral artery (MCA) stroke with a corresponding vessel occlusion. The 76-year-old female patient had extensive CSS and numerous cerebral microbleeds and received another IVT treatment for recurrent MCA stroke 8 months after the first event. After both IVTs, she had clinically asymptomatic small ICH outside the ischemic infarct and distant from CSS. The 2 other patients had only mild to moderate CSS and did not experience any ICH on postthrombolytic imaging. Conclusions: The prevalence of CSS in a clinical cohort of stroke patients that received IVT was low and thus does not appear to pose a substantial risk for symptomatic ICH although this may occur in individual patients. However, such analysis also needs to be extended to the very old stroke patients in whom IVT is increasingly used.

Acute diffusion-weighted imaging lesions in cerebral amyloid angiopathy-related convexal subarachnoid hemorrhage:

Small acute diffusion-weighted imaging (DWI) lesions can accompany intracerebral hemorrhage due to cerebral amyloid angiopathy (CAA). We therefore examined the occurrence of such lesions in the context of CAA-related convexal subarachnoid hemorrhage (cSAH) both in a cross-sectional and longitudinal manner. DWI lesions were noted in 14/29 (48%) patients at their index cSAH and 12/21 patients (57%) showed acute small DWI lesions at follow-up MRI. Forty-four of 71 (62%) DWI lesions were spatially related to areas of cortical superficial siderosis. Clarification of the implications of our finding needs the investigation of larger patient groups.

The Johann Jacob Wepfer Award 2015 of the European Stroke Conference to Professor Ralph L. Sacco

He has been the Olemburg Family Chair of the Department of Neurology at the Miller School of Medicine at the University Miami (Florida, USA) for the last 9 years and lately also Executive Director, Evelyn A. McKnight Brain Institute. As if these positions were not enough, he has also just completed his 3-year term as the only Neurologist elected as President of the American Heart Association and is now in the process of becoming the next President of the American Academy of Neurology. He recently received the prestigious Cor Vitae award from the American Heart Association. Those of us who have known him from his earliest career days had no surprise when he succeeded me as the director of the Tananbaum Stroke Center at the Neurological Institute. His immense service in the department of neurology at the University of Miami is a classic example of the metastasis becoming larger the primary. We welcome him as the Johann Jacob Wepfer awardee. This year’s Johann Jacob Wepfer award winner is an internationally famous clinical neurologist who is currently the chairman of the Department of Neurology at the University of Miami in the United States. An engineering graduate from Cornell University, a Medical Graduate from Boston University, he trained in neurology, epidemiology, and stroke at the Doris and Stanley Tananbaum Stroke Center at the New York Neurological Institute of the Columbia University Medical Center in New York. His career development has been meteoric. His curriculum vitae includes over 500 peer-reviewed publications on a wide variety of subjects for stroke; his role has been one of a major investigator in a number of clinical trials. His work as founder and principal organizer of the Northern Manhattan Stroke Study has eclipsed the impact of the Framingham Study with which he was associated as a medical student. Published online: July 18, 2015