Primary angiitis of the central nervous system: an ante-mortem diagnosis.S Singh, T Soloman, G Chacko, TP Joseph
Department of Radiodiagnosis, Christian Medical College and Hospital, Vellore - 632004, India. , India
A rare case of primary angiitis of the central nervous system (PACNS) is reported with its clinical and magnetic resonance imaging (MRI) features. A 20-year-old girl presented with headache, projectile vomiting, unsteadiness of gait and urgency of micturition. She had left seventh nerve upper motor neuron type paresis, increased tone in all four limbs, exaggerated deep tendon reflexes, cerebellar signs, and papilloedema. Cerebrospinal fluid showed lymphocytosis with elevated protein and normal glucose level. Cerebral computerised tomographic scan and MRI showed bilateral diffuse asymmetric supra- and infra-tentorial lesions (predominantly in the supratentorial and left cerebrum). On MRI, the lesions were hyperintense on T2, and proton density-weighted images and hypointense on T1-weighted images. Based on the clinical findings of raised intracranial tension and MRI features, initial diagnoses of gliomatosis cerebrii, tuberculous meningitis, primary central nervous system lymphoma and chronic viral encephalitis were considered. PACNS was not included in the initial differentials and, an open brain biopsy was advised which established the definitive diagnosis.
Keywords: Adult, Case Report, Fatal Outcome, Female, Human, Intracranial Pressure, Magnetic Resonance Imaging, Pregnancy, Vasculitis, Central Nervous System, diagnosis,pathology,physiopathology,
Primary angiitis of the central nervous system (PACNS) is a rare disorder of unknown aetiology, characterised by non-specific granulomatous inflammation of the media and adventitia of small cerebral parenchymal and leptomeningeal arteries and veins.,, The clinical criteria of establishing a definitive ante-mortem diagnosis include combination of clinical presentation, exclusion of systemic inflammation and infection, angiographic findings, and leptomeningeal or parenchymal biopsy, which is a gold standard., The computerised tomographic (CT) and magnetic resonance imaging (MRI) findings are non-specific, and the diagnosis is usually based on exclusion of other similarly appearing entities.,,
A 20-year-old girl was presented with episodes of holocranial headache associated with projectile vomiting, which partially relieved her symptoms, and diplopia of seven months’ duration. She also had history of unsteadiness of gait and urgency of micturition for the past six months. Neurological examination revealed left seventh cranial nerve paresis of upper motor neuron type. Motor system showed increased tone in all the four limbs without wasting or fasciculations. The superficial abdominal reflexes were absent on both sides with up-going right planter reflex. Deep tendon reflexes were exaggerated bilaterally. She also had bilateral cerebellar signs. The fundoscopy showed bilateral papilloedema. Her mini-mental status examination was normal. Cerebrospinal fluid (CSF) showed lymphocytosis with elevated protein and normal glucose level and culture was negative. Collagen vascular work-up, ESR and the blood and bone marrow cultures were normal.
Cerebral CT and MRI showed bilateral diffuse asymmetric supra- and infra-tentorial lesions (predominantly in the supratentorial and left cerebrum). On MRI, the lesions were hyperintense on T2, and proton density-weighted images [Figure:1A] & [Figure:1B], and hypointense on T1-weighted images [Figure:2A]. The lesions were predominantly in the deep and periventricular white matter and centrum semiovale with involvement of the subcortical white matter and the cortex. The basal ganglia, internal and external capsules, and the right cerebral peduncle were involved. A small area of bleed in the left temporal cortex was seen. The post-gadolinium images showed multiple small nodular and linear enhancing areas with involvement of the sulci, cisterns and the leptomeninges [Figure:2B]. Few linear enhancing areas were also seen in the posterior fossa.
Depending on the clinical features, and the MRI features, sis cerebrii, tuberculous meningitis, and primary central nervous system (CNS) lymphoma were considered, and the open brain biopsy was suggested for a definitive diagnosis. PACNS was not suspected, and therefore an angiography was not performed.
The biopsied specimen showed diffuse granulomatous and non-granulomatous vasculitis in the leptomeninges and brain parenchyma [Figure - 3]. The granulomas contained both foreign body and Langhans type giant cells. The non-granulomatous inflammation was chiefly composed of lymphocytes and mononuclear inflammatory cells. No fibrinoid necrosis was seen. Some of the vascular channels showed fibrous thickening of their walls. Special stain for acid-fast bacilli and fungus were negative.
She was treated with cyclophosphamide, prednisolone, and azathioprine, and showed good clinical improvement. A follow-up MRI was not done.
The primary angiitis of the central nervous system is non-infectious granulomatous arteritis with a predilection for the CNS.,, Isolated involvement is the characteristic of PACNS that may or may not be proved on neuroimaging. It is usually seen in the middle age with no sex predilection. Histopathologically, there is a granulomatous reaction that results in multiple foci of ischaemic or haemorrhagic infarctions secondary to vessel wall proliferation with resultant luminal obliteration, thrombotic occlusion, or rupture of necrotic vessels wall. Symptomatology is variable, and usually includes headache, focal or global neurological dysfunction, confusion, intellectual deterioration, memory loss, and malaise. It may present as focal or multiple strokes, encephalopathy or seizures in association with headache. Fever, myalgia, arthralgia, and arthritis may also occur. Increased ESR and CSF pleocytosis with increased protein levels maybe seen.
MRI is more sensitive than the CT., On MRI, the long TR images show hyperintense foci representing ischemia or infarction. The common findings are multiple bilateral supratentorial infarcts involving the both grey and white matter, predominantly in the deep white matter, corpus callosum and capsular tract., Less commonly, it presents as brainstem lesions, primary parenchymal haemorrhage or simulates primary brain tumour.,, Unlike our case, most of the cases do not show infratentorial involvement.,, New lesions may appear on follow up studies, and other pre-existing lesions may decrease in prominence or disappear. The pattern of enhancement maybe variable; irregular subcortical streaks, punctate areas, and leptomeningeal enhancement with little parenchymal involvement, focal cortical ribboning or diffuse parenchymal vessel enhancement has been reported., 
The findings on cerebral angiography are non-pathognomonic, and its sensitivity over MRI is debated. Alhalabi and Moore suggested that the angiography is more sensitive than MRI., Greenan et al have reported cases with positive findings on angiography and normal MRI. Cerebral angiogram may show stenosis, irregular narrowing, multiple focal dilatation, beading or sausage pattern in multiple vessels, small aneurysms, and avascular masses.,
The diagnosis begins with a high index of suspicion based upon the symptoms, signs and laboratory studies at first presentation. Rarity of this entity led us not to consider it in the initial differential diagnosis. The patient’s history of raised intracranial pressure (ICP), CSF picture of a lymphocytic pleocytosis, raised protein with normal glucose excludes chronic bacterial or fungal meningitis. The triad of MRI findings of asymmetrical cortical and subcortical enhancements, areas of bleed and leptomeningeal enhancements could be consistent with an angiitis process. And, the bleed also points to suspect angiitis. A normal mental status with headache, bilateral papilloedema, and the relatively slow seemingly indolent course also favours a non-infectious CNS inflammatory process. Primary CNS lymphoma and gliomatosis cerebri etc. may not give rise to above trail especially with bleed.
Brain and meningeal biopsy is the gold standard for the diagnosis., Preferred site for the brain and meningeal biopsy is the temporal lobe of non-dominant side in areas with a longitudinally arranged surface vessel., Brain biopsy from cortical tissue and leptomeninges should be taken to avoid sample errors due to skip lesions. It is certainly warranted, if there is no cause to explain a clinical syndrome of encephalopathy prolonged over days or weeks, especially with local cerebellar signs and raised CSF protein and pleocytosis, with or without signs suggestive of angiitis on brain MRI or cerebral angiography.
In conclusion, in a patient with raised ICP, and the above described CSF and MRI features, a differential diagnosis of primary angiitis of the CNS should also be considered, and a brain/ leptomeningeal biopsy should be advised for a definitive diagnosis.
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4]