Three in and three out?

What are the causes of recurrent intracranial hemorrhage in young patients? Have you thought of this rare cause? Recently, Neurology magazine reported a case of repeated intracranial hemorrhage in a 23-year-old man
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Let's learn about the causes behind it .

Yimaitong compiles and organizes, please do not reprint without authorization
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Case introduction The patient is a 23-year-old man with right-handed hands.
He went to the doctor for "emergency left hemiplegia, numbness and dysarthria"
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CT of the head showed intraparenchymal hemorrhage (IPH) in the right frontal lobe
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Since the patient had experienced 2 IPH of unknown etiology 4 months before admission, he was referred to a tertiary care center
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Four months ago, the patient had generalized tonic-clonic seizures.
At that time, a CT scan of the head showed IPH in the right parietal lobe
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Head MRI plain scan and enhancement showed multiple small magnetically sensitive low-intensity lesions in the deep white matter (considering microhemorrhage), enhancement of the right parietal pia mater and enhancement of the right temporal lobe parenchyma
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The patient underwent cerebral angiography to assess vascular malformations.
The results showed mild multifocal stenosis of the right middle cerebral artery (Figure 1, D), and bilateral intracranial internal carotid arteries were tapered in appearance, but the significance was unknown
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C-reactive protein (CRP) increased to 70.
5, erythrocyte sedimentation rate (ESR) increased to 24, but anti-neutrophil cytoplasmic antibody (ANCA), anti-nuclear antibody, CSF oligoclonal band (OCB) and immunoglobulin G (IgG) synthesis rate/index are all within the normal range
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Blood pressure is normal, and neurological examination is normal
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Before making the final diagnosis, the patient was asked to be discharged from the hospital, and it is recommended to maintain anti-epileptic drug treatment and to review the head MRI 4-6 weeks later
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Two months ago, the patient had sudden difficulty in finding words and headache.
CT examination of the head showed acute IPH in the left frontal lobe
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Head MRI showed multiple new microhemorrhages, but no new enhancement lesions
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Repeated angiography showed no segmental stenosis
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Re-examination of CRP showed that it was normal
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The symptoms disappeared within a few days, and the neurological examination was normal
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In view of the relief of segmental cerebrovascular stenosis, the patient was diagnosed with reversible cerebral vasoconstriction syndrome (RCVS), which was considered to be caused by daily use of marijuana, was discharged from the hospital and recommended to stop using marijuana
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Two months later, the patient experienced left weakness and dysarthria again, which improved within a few days
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The previous hemorrhage area on the cranial MRI showed hemorrhage again, but multiple new microhemorrhage lesions were shown in the superficial and deep parts of the entire tentorium, and there were multiple curve-like enhancement lesions (Figure 1, E and F), making it necessary Consider vasculitis
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Lumbar puncture showed an increase in lymphocytes (67 cells/mm3, 94% lymphocytes), increased protein levels (94 mg/dL), 3 OCBs, IgG index (1.
05, normal 0.
28-0.
66) and IgG The synthesis rate (32.
4 mg/d, normal <8.
0 mg/d) increased, indicating inflammation of the central nervous system; the cerebrospinal fluid red blood cell count increased (3,000 cells/mm3), which may be due to acute IPH; the cerebrospinal fluid glucose level is normal
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Serum inflammation tests such as CRP, ESR, complement, ANCA, rheumatoid factor, and serum protein electrophoresis were all within the normal range
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Infectious tests such as hepatitis B, hepatitis C, HIV, rapid plasma reagin, and herpes simplex virus were all negative
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Quantiferon gold tuberculosis test is weakly positive.
Given the exposure history of family members, the possibility of tuberculosis needs to be considered
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After consultation with the Department of Infectious Diseases, it was believed that the quantitative analysis might be a false positive, but out of prudent consideration, it is recommended to use rifampicin for treatment
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CT examination of the chest, abdomen, and pelvis found no evidence of infection or tumor
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Due to the unclear diagnosis, the patient underwent a brain biopsy.
The pathological results (Figure 1, AC) showed small vessel inflammation, consistent with chronic and active vasculitis; focal granuloma formation was accompanied by leptomeningitis and encephalitis
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Acid-fast staining was negative
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Fungal and bacterial cultures were negative
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15s ribosomal RNA infection was negative
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The patient was treated with methylprednisolone (1,000 mg) for 5 days, followed by oral prednisone 100 mg and was discharged from the hospital with a gradual reduction, followed by a reduction of 20 mg every two weeks
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The bacterial PCR result was negative after about 1 week
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At the same time, the patient started taking cyclophosphamide (600 mg/m2/month), and then planned to use azathioprine for maintenance therapy
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During high-dose steroid therapy, the patient also takes Bactrim DS to prevent dust His pneumonia, and supplements with vitamin D and calcium to prevent osteoporosis
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Figure 1 Pathological examination results of brain biopsy and head MRI results
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(A) Diffuse mononuclear cell infiltration can be seen on the surface of the pia mater (arrow, upper part of the figure), extending to the superficial cortex (lower part of the figure)
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(B) Inflammation of pial blood vessels and perivascular inflammation with focal granuloma formation (arrow)
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(C) Some pia mater vessels show complete occlusion, with luminal fibrosis and transmural inflammation (arrow)
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(D) DSA shows multiple stenosis of the right middle cerebral artery (arrow)
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(E) Axial T1 enhanced image showing left frontal lobe and diffuse pial enhancement (arrow)
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(F) T2*weighted image showing multiple bleeding in different periods in the right and left frontal lobes
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 Discussion Primary vasculitis of the central nervous system (PACNS) is a small and medium vasculitis confined to the central nervous system, which affects the brain parenchyma, spinal cord, and meninges
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The disease is relatively rare, with an annual incidence of 2.
4/1,000,000
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When the central nervous system is involved, it is likely to be secondary to systemic inflammatory diseases
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Although brain biopsy is still the gold standard, it has low specificity and a false negative rate of 25%-50%
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Symptoms are variable and non-specific, and may include headaches, focal neurological dysfunction, cognitive impairment, TIA, and ischemic stroke
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ICH is a less common manifestation, but its relationship with PACNS may not be fully understood
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A 25-year cohort study of the PACNS population reported in 2011 showed that about 12.
1% of patients were found to have ICH when they were approaching the diagnosis or when they were diagnosing PACNS
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A recent cohort study of 60 patients showed that 55% had ICH
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Although the data are limited, they indicate that PACNS may be more common for ICH than previously thought
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This case emphasizes that for patients with unexplained ICH, PACNS should be included in the differential diagnosis
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On the second admission, the patient was diagnosed with RCVS, and the clinical manifestations of the disease were similar to PACNS
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RCVS is characterized by reversible contraction of cerebral arteries, which can lead to severe headaches, seizures, focal neurological deficits, and acute ischemic or hemorrhagic strokes
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Some manifestations of PACNS and RCVS overlap, but they can be distinguished by the following points: ➤ Both may have headaches, but RCVS usually suffers from lightning-like headaches.
Research shows that only 6% of RCVS patients have no lightning headaches and relapse Lightning headache has a 100% positive predictive value for the diagnosis of RCVS; RCVS is usually acute, while PACNS may last for several months
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CSF is usually normal and may also reflect cerebral hemorrhage (if present); ➤ On cranial MRI, PACNS is more likely to show strong T2 signal lesions, pia mater enhancement, and deep/brain stem infarction, while RCVS can be normal on MRI Or showing watershed infarction or vasogenic edema, the positive predictive value is 100%
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RCVS and PACNS can show segmental stenosis on cerebral angiography, but they are neither sensitive nor specific
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Segmental stenosis of medium-sized blood vessels can also be found in vasospasm, atherosclerosis, fibromuscular dysplasia and moyamoya disease
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The relief of segmental stenosis after 1-3 months may support the diagnosis of RCVS
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The sensitivity of cerebral angiography to the diagnosis of PACNS is not high, estimated to be about 60%
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PACNS can also be confined to small blood vessels, but it is difficult to detect by conventional cerebral angiography
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This patient has several characteristics that increase the difficulty of distinguishing RCVS from PACNS
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First, the patient’s initial cerebrospinal fluid showed hemorrhage, but other inflammatory markers (cerebrospinal fluid protein, IgG synthesis rate/index, and OCB) were in the normal range; the segmental stenosis seen on the initial cerebral angiography was 2 months After alleviation, RCVS is more supported
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This case illustrates the diagnostic challenge of rare manifestations of rare diseases
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Cerebral hemorrhage is an unrecognized manifestation of PACNS.
For patients with recurrent hemorrhage, this disease should be considered
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                                              Yimaitong compiled from: Jessica Rice, Randall Woltjer, Nicholas Stienstra, Elizabeth Sun, Vijayshree Yadav.
Pearls & Oy-sters: Primary angiitis of the CNS presenting with recurrent intracranial hemorrhage.
Neurology, 2020, 94 (9), e992-e995 .