Primary angiitis of the CNS (PACNS) with predominant cranial neuropathy and spinal cord involvement

We describe a 70‐year old man with a history of repeated epidural injections for chronic low back pain, presenting with headache, cranial nerve palsies and progressive myelopathy. Meningeal enhancement was initially seen in the posterior epidural space of the T₁₀–T₁₂ spine on MRI. Extensive laboratory investigation showed normal or negative results except for persistent pleocytosis, elevated protein and absence of demonstrable microorganisms on CSF studies. Despite conventional and empirical treatments, the patient developed progressive neurological deterioration leading to death. Autopsy showed Primary angiitis of the CNS (PACNS) with predominant cranial neuropathy, spinal cord involvement and extensive myelomalacia.     

Giant cell angiitis of the central nervous system with atypical presentation

Giant cell angiitis of the CNS is an uncommon form of vasculitis. Neurological manifestations, both of the peripheral and CNS, are common. The most frequent manifestations are visual loss and stroke. Hemorrhagic onset is uncommon. Most cases have a fatal outcome and a tissue diagnosis is rarely established in life. We describe an unusual case of giant cell angiitis beginning as a hemorrhagic tumoral‐like lesion. The results of the histological and ultrastructural analysis have also been reported. Our case illustrates that giant cell angiitis should be considered as a cause of intracerebral hemorrhage, particularly when associated with a relapsing and remitting disease of the CNS.     

A case of childhood unilateral relapsing primary angiitis of the central nervous system

The patient was a 17-year-old girl with transient right-sided weakness and dysesthesia associated with headache and nausea. Head magnetic resonance imaging (MRI) revealed white matter lesions confined to the left hemisphere. Initially, multiple sclerosis was suspected, and methylprednisolone (mPSL) pulse therapy was administered, followed by fingolimod hydrochloride. However, on day 267, the patient again experienced transient hypesthesia. Cranial MRI showed expansion of the highly infiltrated areas of the left hemisphere on fluid-attenuated inversion recovery (FLAIR) and T2 weighted image, accompanied by edema. Multiple contrasting areas were also observed. Susceptibility-weighted imaging demonstrated several streaks and some corkscrew-like appearances with low signals from the white matter to the cortex, suggestive of occluded or dilated collateral vessels. Multiple dotted spots indicating cerebral microbleeds (MBs) were also observed. A brain biopsy revealed lymphocytic, non-granulomatous inflammation in and around the vessels. Vascular occlusion and perivascular MBs were prevalent. The patient was diagnosed with relapsing primary angiitis of the central nervous system (PACNS), and immunosuppressive treatment was initiated, mPSL 1000 mg/day pulse therapy. The patient's clinical symptoms and neuroradiological abnormalities gradually improved. She is now receiving oral prednisolone (6 mg/day) and mycophenolate mofetil (1750 mg/day). This case corresponds to unilateral relapsing, which has recently been reported as a specific clinicopathological subtype of PACNS.     

Lyme neuroborreliosis: An unusual case with extensive (peri)vasculitis of the middle cerebral artery

Lyme disease is a tick-borne infection caused by Borrelia burgdorferi sensu latu. Neuroborreliosis is reported in approximately 10% of patients with Lyme disease. We report a patient with central nervous system (CNS) large vessel vasculitis, ischemic stroke, and tumefactive contrast-enhancing brain lesions, an unusual complication of neuroborreliosis. A 56-year-old man presented with headache and disorientation for 1 month. Magnetic resonance imaging revealed basal meningitis with rapidly progressing frontotemporoinsular edema and (peri)vasculitis. Transcranial ultrasound confirmed stenosed medial cerebral arteries. [¹⁸F]GE-180 microglia positron emission tomography (PET) showed frontotemporoinsular signal more pronounced on the right. [¹⁸F]FET amino acid PET demonstrated low tracer uptake, suggesting an inflammatory process. Cerebrospinal fluid (CSF) showed lymphomonocytosis (243/μl), intrathecal anti-Borrelia IgM (CSF/serum index = 15.65, normal < 1.5) and anti-Borrelia IgG (CSF/serum index = 6.5, normal < 1.5), and elevated CXCL13 (29.2 pg/ml, normal < 10 pg/ml). Main differential diagnoses of neurotuberculosis and perivascular CNS lymphoma were ruled out by biopsy and Quantiferon enzyme-linked immunosorbent assay. Ceftriaxone (28 days), cortisone, and nimodipine (3 months) led to full recovery. Neuroborreliosis is an important differential diagnosis in patients with CNS large vessel vasculitis and tumefactive contrast-enhancing brain lesions, mimicking perivascular CNS lymphoma or neurotuberculosis as main neuroradiological differential diagnoses. Vasculopathy and cerebrovascular events are rare in neuroborreliosis but should be considered, especially in endemic areas.     

Cancer therapy-associated CNS neuropathology: an update and review of the literature

Standard therapeutic options for brain tumors include surgery, radiation, and chemotherapy. Unfortunately, these same therapies pose risks of neurotoxicity, the most common long-term complications being radiation necrosis, chemotherapy-associated leukoencephalopathy, and secondary neoplasms. These side effects remain difficult to predict, but are associated with risk factors that include patient age, therapeutic modality and dosage, genetic background, and idiosyncratic predispositions. Experimental treatments designed to enhance efficacy and to minimize neurotoxicity include molecularly targeted, genetic, stem cell, and immune therapies. Newer modifications in radiation and drug delivery include stereotactic radiosurgery, interstitial therapy such as intracavitary brachytherapy and gliadel wafer placement, 3D conformal radiation, boron neutron capture therapy, radiosensitizers, blood–brain barrier disrupting agents, and convection enhanced delivery. Toxicities associated with these newer modalities have yet to be fully investigated and documented. Additionally, a number of recently implemented radiographic techniques such as PET and SPECT imaging have enhanced the ability to distinguish recurrent tumor from radiation necrosis. Nevertheless, post-therapeutic brain biopsies and autopsies remain the gold standard for assessing neurotoxicity, therapeutic efficacy, tumor progression, and the development of secondary neoplasms. At the same time, treatment-associated changes such as tumor necrosis, vasculopathy, inflammation, and cytologic atypia can pose significant diagnostic pitfalls, particularly if the pathologist is not provided a detailed therapeutic history. Therefore, it is critical to recognize the full spectrum of cancer therapy-associated neuropathology, the topic of the current review.     

Sex differences in behavior and neuropharmacology of zebrafish

Sex is an important variable in biomedical research. The zebrafish (Danio rerio) is increasingly utilized as a powerful new model organism in translational neuroscience and pharmacology. Mounting evidence indicates important sex differences in zebrafish behavioral and neuropharmacological responses. Here, we discuss the role of sex in zebrafish central nervous system (CNS) models, their molecular mechanisms, recent findings and the existing challenges in this field. We also emphasize the growing utility of zebrafish models in translational neuropharmacological research of sex differences, fostering future CNS drug discovery and the search for novel sex‐specific therapies. Finally, we highlight the interplay between sex and environment in zebrafish models of sex‐environment correlations as an important strategy of CNS disease modeling using this aquatic organism.     

CNS aspergilloma mimicking tumors: Review of CNS aspergillus infection imaging characteristics in the immunocompetent population

Background and purpose

CNS Aspergillosis is very rare and difficult to diagnose clinically and on imaging. Our objective was to elucidate distinct neuroimaging pattern of CNS aspergillosis in the immunocompetent population that helps to differentiate from other differential diagnosis.

表现为复发性视神经炎的肿块样原发性中枢神经系统血管炎一例报道并文献复习

目的加强对肿块样原发性中枢神经系统血管炎(tl-PACNS)的认识。方法回顾性分析1例经病理证实的tl-PACNS患者的临床、影像学、病理表现以及治疗和预后情况。结果患者临床表现为复发性视神经炎,头MRI表现为肿块样长T1、长T2病灶,术后病理表现为软脑膜和小血管壁上淋巴细胞和浆细胞浸润,对糖皮质激素(激素)单用或联合免疫抑制剂治疗有效。结论 tl-PACNS临床表现复杂多样,影像学上极易误诊为肿瘤,脑活检是其确诊的主要依据。tl-PACNS对激素和免疫抑制剂治疗效果好。     

原发性中枢神经系统血管炎的临床、影像及病理特点研究

目的探讨原发性中枢神经系统血管炎(PACNS)的临床、影像及病理改变特点。方法收集海军总医院2008-2011年间经病理检查确诊的PACNS患者5例(其中经立体定向脑活检4例,开颅活检1例),通过对患者的所有临床资料进行回顾性分析,总结PACNS的临床、影像、病理改变特点。结果临床主要表现为头痛、癫痫、视物模糊、言语不利以及局灶的神经功能缺损。影像学表现:幕上4例,幕上下均累及1例;所有脑叶均可累及;单侧发病3例,双侧发病2例。病灶边界模糊,灰白质均可累及,增强扫描后均有不同程度的脑回样或斑片样强化。病理特点为皮质及白质内可见到小血管周围大量的淋巴细胞浸润,多以T淋巴细胞浸润;可见到坏死及吞噬细胞以及反应性星形细胞增生;小血管增生明显,3例患者可见到血管壁的纤维素样坏死。患者经糖皮质激素+免疫抑制剂治疗,疗效满意。结论 PACNS临床表现以局灶的神经功能缺损为主要表现,病变部位为幕上多发,以单侧发病多见。诊断需结合临床特点、实验室、影像学和病理学检查。     

Juvenile ceroid-lipofuscinosis and calcifications of the CNS

The post-mortem brains and spinal cords of 20 juvenile ceroid-lipofuscinosis (JC-L) cases from 1973 to 1987 were investigated. Clinical course of the disease was characterized by impaired vision from the age of 5-8 years, progressive dementia, seizures, somatic retardation, and early death (16-29 years of age). Microscopy showed classic intracytoplasmic autofluorescent lipopigment in the nerve cells throughout the CNS and viscera. Immunoperoxidase staining for glial fibrillary acidic protein (GFAP) showed marked gliosis with enlarged reactive astrocytes mainly in the superficial layers of the cerebral cortex. Calcifications of the nervous system principally along the outer and inner brain surfaces were demonstrated by X-ray, macroscopic examination and microscopy. We suggest that the calcifications are secondary to a suspected generalized metabolic error.     

A community-based study of incidence,risk factors and outcome of transient ischaemic attacks in Umbria,Italy: the SEPIVAC study

Summary The SEPIVAC study is a community-based epidemiological survey of incidence and outcome of transient ischaemic attacks (TIAs) and strokes in the territory of the 6th Local Health Unit, Umbria, Italy, where 49218 people live, from 1 September 1986 to 31 August 1989. All cases were registered with the study either by notification from general practitioners (GPs) or by a check of hospital admission within the study area and in the two hospitals of Perugia. There were 94 incident cases of TIAs (45 males, 49 females), thus giving a crude rate of 0.64 per 1000 per year [95% conficence intervals (CI) 0.52/0.78]. The rate adjusted to the European population is 0.42 (CI 0.33/0.54). Mean age was 69.4 years, and females were significantly older than males. The weighted relative risk for males was 1.19 (CI 0.79/1.79). Thirty-one patients were treated at home by their GPs. Females had hypertension more frequently than males, whereas males smoked more frequently; we did not find any other statistically significant difference in the distribution of risk factors. Twelve patients out of 58 who had CT had an infarct, and 29 out of 54 submitted to Doppler ultrasonography had carotid stenosis. At 1 month, 4 patients had suffered an ischaemic stroke, 1 of whom died. At 6 months, 3 further strokes and 2 further deaths (1 due to myocardial infarction) had occurred.     

Pitfalls in the diagnosis of reversible cerebral vasoconstriction syndrome and primary angiitis of the central nervous system

A case of a 51-year-old woman with reversible cerebral vasoconstriction syndrome (RCVS) without an associative cause is reported. Initially the diagnosis primary angiitis of the central nervous system (PACNS) was considered. Both diagnosis are rare and can mimic each other. Distinction between both can be difficult, but is necessary because of different treatment options. Clinical features and diagnostic assessments to distinguish RCVS from PACNS and the potential pitfalls are discussed.     

Primary angiitis of the central nervous system: report of five biopsy-confirmed cases from Colombia

INTRODUCTION: Primary (isolated) angiitis of the central nervous system (PACNS) is a rare cause of cerebrovascular disease (CVD), and few leptomeningeal and brain biopsy (LBB)-confirmed cases have been reported from South America. METHODS: We retrospectively reviewed charts of patients with diagnosis of cerebral angiitis admitted between March 1991 and July 2001 to a single university hospital in Medellin, Colombia. Patients with definitive diagnosis of PACNS by Alrawi et al.'s LBB criteria were selected. We excluded other causes of cerebral angiitis as well as cases without LBB confirmation. RESULTS: We report five patients, four men and one woman, with a mean age at onset of 24.4 years, and an average disease progression of 12.4 days. Four presented with headache and motor weakness, three had seizures, and two had alterations of consciousness. Cerebral MRI was abnormal in all five cases; brain CT in four, and cerebral angiography in two. The cerebrospinal fluid (CSF) was abnormal in two patients. Leptomeningeal and brain biopsies revealed mononuclear infiltration in the wall of small blood vessels in all. Three had concurrent meningeal and cerebral involvement, two had necrotizing angiitis, and one had vascular and encephalitic lesions. All received only steroid treatment; the 1-year follow-up revealed good prognosis without relapses. CONCLUSION: We report five biopsy-proven cases of PACNS from Colombia associated with neurological and neuroimaging abnormalities; these patients presented a mild inflammatory disease that was correlated with few CSF abnormalities and good response to single steroid treatment without relapses. Leptomeningeal and brain biopsy is mandatory for a definitive diagnosis.     

Heparan sulphate proteoglycans in glia and in the normal and injured CNS: expression of sulphotransferases and changes in sulphation

Heparan sulphate proteoglycans (HSPGs) have multiple functions relevant to the control of the CNS injury response, particularly in modulating the effects of growth factors and localizing molecules that affect axon growth. We examined the pattern of expression and glycanation of HSPGs in the normal and damaged CNS, and in astrocytes and oligodendrocyte precursors because of their participation in the injury reaction. The composition of HS glycosaminoglycan (GAG) chains was analysed by biochemical analysis and by the binding of antibodies that recognize sulphated epitopes. We also measured levels of HS sulphotransferases and syndecans. Compared with oligodendrocytes, oligodendrocyte precursors have more 2- O -sulphation in their HS GAG. This is accompanied by higher expression of the enzyme responsible for 2- O -sulphation, HS 2- O -sulphotransferase (HS2ST) and a fall in syndecan-1. Astrocytes treated with tumour growth factor (TGF)α or TGFβ to mimic the injury response showed upregulation of syndecan-1 and HS2ST correlating with an increase in 2- O -sulphate residues in their HS GAGs. This also correlated with increased staining with AO4B08 anti-GAG antibody that recognizes high sulphation, and reduced staining with RB4EA12 recognizing low sulphation. After injury to the adult rat brain there was an overall increase in the quantity of HSPG around the injury site, mRNA for HS2ST was increased, and the changes in staining with sulphation-specific antibodies were consistent with an increase in 2- O -sulphated HS. Syndecan-1 was upregulated in astrocytes. The major injury-related change, seen in injured brain and cultured glia, was an increase in 2- O -sulphated HS and increased syndecan-1, suggesting novel approaches to modulating scar formation.     

Nogos and the Nogo-66 receptor: factors inhibiting CNS neuron regeneration

The recently cloned gene Nogo, whose alternative splice products correspond to the antigenic target of the central nervous system (CNS) regeneration enhancing monoclonal antibody IN-1, codes for membrane proteins enriched in brain, particularly in oligodendrocytes. The 66-amino acid extracellular domain of Nogo (Nogo-66) interacts with a high-affinity receptor (NgR), a glycosylphosphatidylinositol (GPI)-linked protein with multiple leucine-rich repeats. The amino terminal cytoplasmic domain of Nogo appears to have a general cellular growth inhibitory effect. Nogo-66, on the other hand, specifically retards neurite outgrowth and induces growth cone collapse, possibly through its interaction with NgR and as yet unidentified transmembrane coreceptors. Recent results also suggest that Nogo expression may induce apoptosis in tumor cells. Together, these proteins provide new molecular handles for the design of therapeutic interventions for CNS injuries and neurodegenerative diseases, as well as possible leads to anticancer strategies.     

Ischaemic intermittent claudication of the masticatory muscles: two case reports

Intermittent claudication of the masticatory muscles is an unusual symptom sometimes described in association with temporal arteritis. We describe here two cases where this symptom was due to insufficient blood supply to the masticatory muscles caused by atherosclerotic changes of carotid vessels. In one of our cases surgical revascularization was followed by the disappearance of this symptom.

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Sommario La „claudicatio intermittens” dei muscoli masticatori è un sintomo piuttosto raro, descritto talora in associazione con l'arterite temporale. Vengono qui riportati due casi in cui questo sintomo era causato da un ridotto apporto ematico ai muscoli masticatori conseguente ad alterazioni di natura arteriosclerotica a carico dei vasi carotidei. In uno dei nostri casi fu effettuato un intervento chirurgico di rivascolarizzazione (endoarteriectomia carotidea) cui conseguì la scomparsa della „claudicatio intermittens” dei muscoli masticatori.

     

Aluminum intoxication and the victim of Alzheimer's disease: similarities and differences

Aluminum (Al) has been implicated in the pathogenesis and may produce a model of senile dementia of the Alzheimer's type (SDAT). To better understand the effects of Al on the mammalian brain, Al was studied in rabbits and rats using several experimental approaches. Similar behavioral toxicity and site and degree of neurofibrillary tangle (NFT) development were obtained after intracerebroventricular (icv) or repeated sc Al, although a more protracted time course after the latter. SDAT victims demonstrate some similar behavioral signs but a different type of NFT. A classically conditioned, defensive reflex (nictitating membrane extension) was used to compare response acquisition, retention, and extinction in Al-exposed and control rabbits of various ages. Both increasing age and Al exposure attenuated these measures, suggesting that advanced age and Al intoxication provide behavioral models of SDAT. A deficit in acquisition of a classically conditioned response (eyeblink) in senile-demented patients has been reported. These cognitive deficits in rabbits occurred after a less than two-fold increase in brain Al. Brain Al in SDAT victims has been reported to be unchanged or slightly increased. Further similarity to SDAT was obtained with 4-aminopyridine (4-AP) which attenuated Al-induced behavioral deficits in rabbits and the Al inhibition of glutamate release from rat hippocampal slices. 4-Aminopyridine has been reported to attenuate behavioral deficits in SDAT patients. A tubulin, GTP binding site was blocked in SDAT victim brain but not in control or Al-intoxicated rabbit brain, indicating a biochemical dissimilarity. In summary, Al-intoxication produces a model of SDAT with many similarities but significant differences.