Follow-up examinations by transcranial Doppler ultrasound in primary angiitis of the central nervous system

BACKGROUND: Primary angiitis of the central nervous system (PACNS) is a rare disease. The definite diagnosis is made upon proof of mononuclear inflammation of the vessel wall on brain biopsy. The diagnosis can also be established on clinical grounds, typical findings on intra-arterial angiography and other investigatory grounds excluding other diseases. Therapy comprises an aggressive immunosuppressive approach. Close monitoring of the patients is mandatory. Transcranial Doppler ultrasound (TCD) has not yet been used to follow up the vasculitic lesions in PACNS. CASE: We report on a 32-year-old female with massive cerebral infarctions secondary to multiple large-vessel stenoses because of probable PACNS. The patient was followed closely by means of TCD. During therapy the cerebral blood flow velocities normalized as displayed by TCD. Clinical improvement followed several days after normalization of cerebral blood flow. CONCLUSIONS: TCD is a valuable noninvasive bedside tool to monitor cerebral blood flow velocities and therapy response in patients with cerebral vasculitis, if large arteries are involved.     

Autoradiographic localization of the GABAA receptor agonist [3H]muscimol in rat cerebral vessels

By the use of combined in vitro radioreceptor binding and autoradiographic techniques with [3H]muscimol as a ligand, we analyzed the distribution of GABAA receptor sites in the arteries of the circle of Willis as well as in the arteries and arterioles of the pial-arachnoid membrane in the rat. [3H]Muscimol was bound by sections of rat cerebral vessels in a manner consistent with the existence of GABAA receptors, with Kd and Bmax values of 46 nM and 0.60 pmol/mg tissue respectively. [3H]Muscimol was bound by the medial layer of cerebral arteries, while no specific binding was observed in the intima, the adventitia and the adventitial-medial border. These findings suggest that the vasodilatory action of GABA on in vitro preparations of cerebral vessels is mediated by muscular receptor sites. The posterior cerebral arteries are richer in [3H]muscimol binding sites than the anterior ones. Pial-arachnoid arterioles, which are of critical importance in controlling local cerebral blood flow, did not exhibit any significant binding of [3H]muscimol. These results may explain the difficulty in manipulating pharmacologically the cerebral tissue perfusion in intact animals using GABAergic agonists.     

Reversible cerebral vasoconstriction syndrome or primary angiitis of the central nervous system?

BACKGROUND: Reversible Cerebral Vasoconstriction Syndrome (RCVS) may present as thunderclap headache (TCH), accompanied by reversible cerebral vasospasm and focal neurological deficits, often without a clear precipitant. RCVS may be mistaken for Primary Angiitis of the Central Nervous System (PACNS) due to the presence of similar angiographic features of segmental narrowing of cerebral arteries. We discuss the clinical features of a young female migraine patient who developed TCH and was found to have RCVS following initial treatment with corticosteroids for PACNS, in the context of a systematic review of the available medical literature. METHODS: A Medline search was performed to identify all case reports since 1966 describing RCVS and PACNS that provide sufficient clinical detail to permit diagnostic classification according to published criteria. RCVS included case studies in which there was angiographic or transcranial Doppler ultrasound evidence of near-to-complete resolution of cerebral vasoconstriction in the absence of a well-recognized secondary cause. PACNS included reports of histologically confirmed PACNS either through biopsy or necropsy. RESULTS: Reversible Cerebral Vasoconstriction Syndrome occurs primarily in females and is characterized by sudden, severe headache at onset, normal CSF analysis, vasoconstriction involving the Circle of Willis and its immediate branches, and angiographic or TCD ultrasound evidence of near-to-complete vasospastic resolution within 1-4 weeks. It occurs typically in the context of vasoconstrictive drug use, the peripartum period, bathing, and physical exertion. CONCLUSION: Initial and follow-up (within 4 weeks) non-invasive angiographic studies are indicated in patients who present with TCH or who have clinical presentations that could be consistent with RCVS or PACNS in the absence of a well-recognized secondary cause, such as subarachnoid haemorrhage. Early reversibility of cerebral vasospasm is the key neuroradiological feature that supports the clinical diagnosis of RCVS.     

An autopsy case of subarachnoid and intracerebral hemorrhage and necrotizing angitis associated with methamphetamine abuse

We report an autopsy case of methamphetamine-related intracranial hemorrhage and vasculitis. The possible relationship between drug usage and the occurrence of intracranial bleeding and cerebral vasculitis in such patients is discussed. A 22-year-old woman died after an intravenous injection of unknown dose of methamphetamine. A computed tomography head scan demonstrated massive subarachnoid hemorrhage and hematoma in corpus callosum. Cerebral angiography revealed nonfilling of bilateral intracranial carotid arteries and extravasation of contrast medium from right pericallosal artery which was visualized retrogradely via vertebral artery. Postmortem studies showed cerebral edema, subarachnoid and intracerebral hemorrhage, and intracranial vasculitis in the absence of aneurysm, arteriovenous malformation or chronic hypertension. Histological findings of necrosis of blood vessel walls with destruction of the elastica and smooth muscle layer, and without leukocytotic infiltration of the blood vessel walls were observed in order of anterior cerebral, middle cerebral, vertebral, posterior cerebral and basilar arteries. These angiographic and histological evidence suggests that such hemorrhage results from the development of fibrinonecrosis in the large intracerebral vessels, in addition to a sudden rise in blood pressure.     

Primary angiitis of the central nervous system: report of eight cases from a single Italian center

The primary angiitis of the central nervous system (PACNS) is a rare and potentially fatal form of vasculitis with unknown etiology. Headache and encephalopathy are the most frequent symptoms. Neuroimaging plays an important role in the diagnosis, but the pattern of abnormal findings is not specific. In some cases brain biopsy is mandatory. PACNS is often described as a diagnostic and therapeutic challenge for clinicians considering the lack of univocal diagnostic criteria and paucity of studies evaluating the long-term outcome. This brief work reports how we managed eight patients with PACNS from diagnosis to long-term follow up treatment. Headache and focal acute neurological deficits were the most common symptoms. Magnetic resonance imaging (MRI) was abnormal in all patients with different patterns of infarctions or intraparenchymal/subarachnoid hemorrhages or their combination. Cerebral angiography demonstrated pathological findings compatible with vasculitis in all cases. Other causes of encephalopathy were ruled out. Patients with severe clinical and neuroradiological findings were treated with steroids and immunosuppressive therapy using cyclophosphamide/methotrexate. Patients with less aggressive PACNS, were treated with steroids only. In one case with multiple relapses infliximab was used after first-line immunosuppressive therapy failure. PACNS suspicion is based on the combination of demographic/clinical and MRI findings and the exclusion of other causes of multifocal encephalopathy. A positive angiography has a diagnostic value in an adequate clinical field. A strict collaboration of neurologists, neuroradiologists, and immunoreumatologists is essential in the management of PACNS both in the diagnostic and therapeutic phases.     

CADASIL mimicking primary angiitis of the central nervous system

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and primary angiitis of the central nervous system (PACNS) share several clinical and radiological features. However, digital subtraction angiogram (DSA) is generally reported as normal in CADASIL, whereas lumen irregularities in distal cerebral arteries indicate PACNS. OBJECTIVE: To describe a potential pitfall of DSA interpretation, which led to the tentative diagnosis of PACNS in a CADASIL patient. PATIENT AND METHODS: Single case observation. RESULTS: A 47-year-old man sustained recurrent subcortical infarcts. He had mild hypercholesterolemia and migraine. His family history was unremarkable. The underlying cause of stroke could not be elucidated. Transcranial Doppler sonography revealed decreased intracranial blood flow velocities compatible with CADASIL. Lumen irregularities of several peripheral intracranial arteries were seen on DSA, which suggested PACNS. CADASIL was confirmed by results from skin biopsy and genetic testing. CONCLUSIONS: First, in patients with CADASIL, DSA can show segmental lumen irregularities in distal cerebral arteries suggestive of PACNS. Second, the potential role of transcranial Doppler sonography to distinguish CADASIL from PACNS deserves further testing.     

Autoradiographic localization of the GABAA receptor agonist [H]muscimol in rat cerebral vessels

By the use of combined in vitro radioreceptor binding and autoradiographic techniques with [³H]muscimol as a ligand, we analyzed the distribution of GABA_A receptor sites in the arteries of the circle of Willis as well as in the arteries and arterioles of the pial-arachnoid membrane in the rat. [³H]Muscimol was bound by sections of rat cerebral vessels in a manner consistent with the existence of GABA_A receptors, with K_d and B_max values of 46 nM and 0.60 pmol/mg tissue respectively. [³H]Muscimol was bound by the medial layer of cerebral arteries, while no specific binding was observed in the intima, the adventitia and the adventitial-medial border. These findings suggest that the vasodilatory action of GABA on in vitro preparations of cerebral vessels is mediated by muscular receptor sites. The posterior cerebral arteries are richer in [³H]muscimol binding sites than the anterior ones. Pial-arachnoid arterioles, which are of critical importance in controlling local cerebral blood flow, did not exhibit any significant binding of [³H]muscimol. These results may explain the difficulty in manipulating pharmacologically the cerebral tissue perfusion in intact animals using GABAergic agonists.     

24例原发性中枢神经系统血管炎患者的MRI表现

目的观察24例原发性中枢神经系统血管炎(PACNS)的磁共振成像(MRI)表现,探讨PACNS的MRI诊断价值。方法对急性期进行了MRI检查的24例经病理证实的PACNS的MRI特点进行了回顾性分析。结果 24例患者中,病灶以幕上多见[19例(79.2%)],最常累及颞叶、额叶、顶叶及基底节区(包括丘脑),分别为13例(54.2%)、10例(41.7%)、8例(33.3%)、8例(33.3%);大部分病灶累及双侧大脑半球[15例(72.5%)],灰质和白质均受累[21例(87.5%)]。MRI上病灶可多发或单发,均为12例(50%)。病灶形态大致可分为四种类型:斑片状、肿块样、脑回状和混合性,分别为12例(50%)、8例(33.3%)、2例(8.3%)和2例(8.3%)。MRI上所有病灶均呈长(稍长)T1WI、长(稍长)T2WI异常信号,增强扫描可见病灶均有强化,FLAIR上均呈高或稍高信号,9例(37.5%)病灶中心呈散点状短T1WI、短T2WI混杂信号。17例行DWI和ADC序列检查者中,9例(52.9%)在DWI上呈高(稍高)信号,ADC上呈等信号或混杂信号影,8例(47.1%)在DWI及ADC上呈等信号。11例行GRE序列检查者,8例(72.7%)可见病灶局部有点状低信号影或病灶周围血管影增粗,余3例未见异常。8例行MRA序列检查者,仅1例发现异常,可见病灶供血区相应血管局部有狭窄。结论本组24例PACNS患者急性期头MRI均有异常,表现多样,病灶以幕上多见,可累及各个脑区,病灶可多发或单发,多数灰白质均受累。其形态可表现为斑片状、肿块样、脑回状或混合性,增强扫描均可见强化,以斑片状或脑回样强化多见。头MRI上病灶多变、灰白质受累、斑片状或脑回样强化等表现对PACNS诊断有一定提示性。     

Role of soluble guanylate cyclase in dilator responses of the cerebral microcirculation

Responses of cerebral blood vessels to nitric oxide (NO) are mediated by soluble guanylate cyclase (sGC)-dependent and potentially by sGC-independent mechanisms. One sGC-independent mechanism by which NO may produce vasodilatation is inhibition of formation of a vasoconstrictor metabolite produced through the cytochrome P450 pathway. In these experiments, we examined the hypothesis that dilatation of cerebral microvessels in response to NO is dependent on activation of sGC. Diameters of cerebral arterioles (baseline diameter=94+/-5 micrometers, mean+/-S.E.) were measured using a closed cranial window in anesthetized rabbits. Under control conditions, YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole], an NO-independent activator of sGC, produced vasodilation that was blocked by ODQ (1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one)(10 microM), an inhibitor of sGC. These findings indicate that sGC is functionally important in cerebral arterioles. In addition, acetylcholine (which stimulates endogenous production of NO by endothelium) produced dilatation of cerebral arterioles that was inhibited by ODQ. For example, 1 microM acetylcholine dilated cerebral arterioles by 34+/-7 and 5+/-1% in the absence and presence of ODQ (10 microM), respectively. Increases in arteriolar diameter in response to sodium nitroprusside (1 microM, an NO donor) were inhibited by approximately 80% by ODQ, but were not affected by 17-ODYA (10 microM) or clotrimazole (10 microM), inhibitors of the cytochrome P450 pathway. Thus, dilatation of the cerebral microcirculation in response to exogenously applied and endogenously produced NO is dependent, in large part, on activation of sGC.     

Reversible cerebral vasoconstriction syndromes and primary angiitis of the central nervous system: clinical,imaging, and angiographic comparison

Reversible cerebral vasoconstriction syndromes (RCVS) and primary angiitis of the central nervous system (PACNS) are invariably considered in the differential diagnosis of new cerebral arteriopathies. However, prompt and accurate diagnosis remains challenging. Here we compared the features of 159 RCVS to 47 PACNS patients and developed criteria for prompt bedside diagnosis. Recurrent thunderclap headache (TCH), and single TCH combined with either normal neuroimaging, border zone infarcts, or vasogenic edema, have 100% positive predictive value for diagnosing RCVS or RCVS‐spectrum disorders. In patients without TCH and positive angiography, neuroimaging can discriminate RCVS (no lesion) from PACNS (deep/brainstem infarcts). Ann Neurol 2016;79:882–894     

Scleroderma,stroke, optic neuropathy: a rare association

A known case of scleroderma presented with right hemiparesis, focal seizures, optic atrophy and gangrene of digits. There was no evidence of peripheral nerve or muscle involvement. MRI showed multifocal infarcts in both cerebral hemispheres. MR angiography revealed poor flow in bilateral carotid arteries with collateralization from posterior circulation. She improved with phenytoin, nifedipine, antibiotics and immunosuppressants. The rarity of central nervous system affliction in scleroderma and large vessel vasculitis is discussed along with review of literature.     

Neuroborreliosis-associated cerebral vasculitis: long-term outcome and health-related quality of life

Neuroborreliosis affects the nervous system after systemic infection with the spirochete Borrelia burgdorferi. Previously, cerebral vasculitis has been regarded as an extremely rare complication of neuroborreliosis. The data on the long-term outcome in patients with cerebral vasculitis due to neuroborreliosis are limited. The objective of this study was to perform a longitudinal analysis of cases of neuroborreliosis-associated cerebral vasculitis. We recruited all patients (n = 11) diagnosed with neuroborreliosis-associated in three neurological departments in an East German region. Inclusion criteria were sudden neurological deficits, magnetic resonance (MR) imaging findings that conform to cerebral ischemia or brain infarction, intrathecal synthesis of borrelia-specific antibodies, and non-atherosclerotic pathology of brain supplying arteries. Vasculitic changes were detected by digital subtraction angiography, MR angiography and/or transcranial Doppler ultrasound. Outcomes were measured by the modified Rankin scale (mRS) and EuroQoL Index. Cerebral vasculitis is a rare complication of Lyme disease (0.3 % of all cases in the endemic area). Ten out of 11 patients diagnosed with neuroborreliosis-associated vasculitis cerebral vasculitis using clinical, radiological and immunological criteria developed ischemic stroke or transient ischemic attacks (TIA), 7 patients had recurrent stroke. Vasculitic alterations could be demonstrated in 8 patients that all except one developed ischemic lesions. The median mRS was 3 (range 0–4) at admission and 2 (range 0–6) at discharge. The posterior circulation was affected in 8 of 11 patients; thrombosis of the basilar artery was detected in 2 patients, one died in the acute stage. Neuroborreliosis can cause recurrent stroke or TIA on the basis of cerebral vasculitis. Lumbar puncture is needed for detection of this potentially life-threatening condition. Early recognition and adequate therapy would possibly improve outcome.     

Absence of acute cerebral vasoconstriction after cocaine-associated subarachnoid hemorrhage

Introduction: Cocaine use has been associated with neurovascular complications, including arterial vasoconstriction and vasculitis. However, there are few studies of angiographic effects of cocaine on human cerebral arteries. Information on these effects could be obtained from angiograms of patients with cocaine-associated subarachnoid hemorrhage (SAH) who underwent angiography shortly after cocaine use. Methods: We screened patients with SAH retrospectively and identified those with positive urine toxicology for cocaine or its metabolites. Quantitative arterial diameter measurements from angiograms of these patients were compared to measurements from control patients with SAH who were matched for factors known to influence arterial diameter. Qualitative comparisons of small artery changes also were made. Results: Thirteen patients with positive cocaine toxicology were compared to 26 controls. There were no significant differences between groups in the mean diameters of the intradural internal carotid, sphenoidal segment of the middle cerebral, precommunicating segment of the anterior cerebral, or basilar arteries (p greater than 0.05 for all comparisons, unpaired t-tests). There also were no significant differences between groups when expressing diameters as the sum of the precommunicating segment of the anterior cerebral + sphenoidal segment of the middle cerebral + supraclinoid internal carotid artery + basilar artery divided by the diameter of the petrous internal carotid artery (p greater than 0.05, unpaired t-tests). Qualitative assessments showed two arterial irregularities in the distal vasculature in each group. Conclusion: No quantitative evidence for narrowing of large cerebral arteries or qualitative angiographic evidence for distal narrowing or vasculitis could be found in patients who underwent angiography after aneurysmal SAH associated with cocaine use.     

Cerebral vasculitis in coccidioidal meningitis

Cerebral vasculitis producing focal central nervous system manifestations was observed in 2 patients with meningitis due to Coccidioides immitis. Cerebral angiography demonstrated the characteristic changes of arteritis, including irregular narrowing of arteries at the base of the brain in 1 patient and occlusion of a middle cerebral artery branch in the other. Pathological examination of the brain in the latter patient revealed extensive basilar meningitis along with prominent vasculitis and organisms. One patient responENd to intrathecal and intravenous amphotericin B treatment combined with a ventriculopleural shunt, the other died despite amphotericin B therapy.     

Multiple Giant Intracranial Aneurysms Associated with Lymphomatoid Granulomatosis: A Magnetic Resonance Imaging and Angiographic Study

Lymphomatoid granulomatosis is an uncommon lymphoproliferative disorder that frequently has central nervous system manifestations. Lymphomatoid granulomatosis has clinical features similar to both vasculitis and lymphoma. The pathological hallmarks of this disease include necrotic angiecentric and angiodestructive infiltrations of premalignant or malignant lymphoid cells. There are, to the authors' knowledge, only a few magnetic resonance imaging reports and no magnetic resonance angiographic reports of this disorder. Presented here is a case of lymphomatoid granulomatosis producing multiple giant fusiform and saccular aneurysms throughout the major intracerebral arteries, along with patterns of vascular beading typically seen with vasculitis demonstrated by magnetic resonance angiography.     

Cerebral Vasculitis: Diagnosis and Follow-Up With Transcranial Doppler Ultrasonography

The authors report a patient with postpartum intracerebral hemorrhage associated with cerebral vasculitis. Cerebral circulation was assessed with transcranial Doppler (TCD) ultrasonography, magnetic resonance angiography, and conventional cerebral angiography. Initial TCD studies demonstrated bilateral patchy increased cerebral blood flow velocity (CBFV) in the anterior circulation with complete normalization during remission. This case report provides evidence that cerebral vasculitis leads to relevant CBFV changes and that the TCD technique may assist in diagnosis and follow-up of these patients.     

The utility of contrast-enhanced MR-angiography for posterior fossa giant cerebral aneurysm management

Abstract

The utility of magnetic resonance angiography is sometimes 1imited in the diagnostic workup of cerebral aneurysms with low flow and/or partial thrombosis when weighed against digital subtraction angiography. We present the case of a rare superior cerebellar artery giantl partially thrombosed aneurysm in which additional i.v. contrast-enhanced MRA sequences were comparable to digital subtraction angiography. It demonstrated not only the exact spatial resolution and correct anatomical relation but also the hemodynamics which were confirmed by intraoperative Doppler ultrasound. This report supports the feasibility and utility of i. v. contrast-enhanced MRA for posterior fossa giant cerebral aneurysm management. [Neural Res 1998; 20: 705-708]     

大面积外伤性脑梗死的血管成像特点与手术疗效

目的探讨大面积外伤性脑梗死（traumatic cerebral infarction,TCI）的梗死区CT血管造影（CTA）成像特点及手术治疗效果。方法回顾性分析34例大面积TCI病例资料,采用CTA观察梗死区血管情况。并采取扩容、解痉、高压氧等综合治疗措施。结果 TCI闭塞血管主要为大脑中动脉、大脑前动脉或大脑后动脉以及基底动脉的远端小动脉或脑深部穿支血管和皮质小血管,未见大脑前动脉、大脑中动脉和大脑后动脉或基底动脉的主干血管闭塞。手术治疗28例,保守治疗6例。随访4~28个月,按GOS评分标准,恢复良好12例,中残8例,重残4例,植物生存3例,死亡7例。结论大面积TCI闭塞的血管主要为脑深部的穿支血管和皮质小血管,早期采取减压手术等综合治疗可取得较好疗效。     

Cerebral vasculitis as presenting symptom of systemic lupus erythematosus

A 42-year-old woman developed right-sided hemiparesis due to left-sided encephalomalacia revealed by CT scan. Subsequent angiography revealed vasculitis of several intra-cranial arteries. The ESR was 65 mm/h. Further laboratory tests revealed no evidence of systemic disease so that no causal diagnosis could be posed. Treatment with prednisone (3 X 30 mg daily) led to complete cure of the hemiparesis within 6 weeks. Sixteen months later, the patient developed cutaneous lesions in the neck. Histological examination of these lesions indicated the presence of systemic lupus erythematosus (SLE). Neurological presentation of SLE is exceptional, while cerebral vasculitis as initial symptom of SLE has never been described before.