Unilateral Asymptomatic Multiple Cerebral Microbleeds: A Very Rare Radiological Entity

A 75-year-old woman with diabetes and hypertension, without any prior neurological complaints, presented with altered sensorium following a febrile illness lasting 2 days. During examination, she showed a Glasgow Coma Scale of 12, without any lateralization signs, and meningeal signs with bilateral plantar flexor response. Her baseline metabolic parameters showed a serum glucose of 210 mg/dl, serum sodium level of 124 mg/l, white blood cell count of 13,500 with 80% neutrophils, and normal platelet count (2.8 lakhs/mm3). Liver function and thyroid function tests were normal. Her serum urea level was 54 mg/dl and creatine was 2.2 mg/dl. Serum osmolality was low (250 mOsm/kg). The patient’s urinary examination revealed the presence of 12–15 pus cells, while the urine culture showed Escherichia coli growth. Her urinary osmolality was high at 920 mOsm/kg. She was diagnosed with hyponatremia secondary to the syndrome of inappropriate anti-diuretic hormone (SIADH), along with urinary tract infection and sepsis. The patient was treated with 3% hypertonic saline, and fluid intake was restricted. She was also administered antibiotics as per culture and sensitivity, which significantly improved her symptoms. A left-handed magnetic resonance imaging (MRI) scan was done. MRI of the brain [Figure 1] showed multiple hypointense lesions of varying sizes (3–8 mm) seen on susceptible-weighted (SW) images in the right cerebral hemisphere, which appeared hyperintense on phase images, suggesting multiple cerebral microbleeds (CMBs). There were no sulcal subarachnoid hemorrhages. In view of raised serum creatine contrast, MRI of the brain was not done in our case. Cerebrospinal fluid, MRI of the spine, angiogram brain, and electroencephalogram showed no significant abnormalities.Figure 1: MRI of the brain, diffusion-weighted image (a) reveals diffuse brain atrophy without any evidence of diffusion restriction. Axial T1-WI (b) shows volume loss. Axial T2-WI (c) and FLAIR (d) show multiple hypointense lesions (arrows) in the right cerebral hemisphere with periventricular hyperintensity around bilateral frontal and occipital horns. Susceptible-weighted image (e) shows multiple rounded hypointense lesions (blooming artifacts) of size 3–8 mm in the right cerebral hemisphere involving predominantly the cortex and a few subcortical lesions, and these lesions appear hyperintense (bright) on the corresponding phase images (f) in left-handed MRI system. Features are consistent with multiple right hemispheric cerebral microbleeds. MRI angiogram (g) is normal. FLAIR: fluid-attenuated inversion recovery, MRI: magnetic resonance imaging. T1-WI: T1-weighted image, T2-WI: T2-weighted imageCMBs are small, rounded, or elliptical lesions with a size of 2–10 mm. They are perivascular hemosiderin depositions detectable by gradient echo sequences or SW imaging.[1] CMBs, also known as microhemorrhages, appear as dark (hypointense) areas in images taken using T2*-weighted or SW imaging techniques. The appearance of CMBs on imaging is primarily due to changes in local magnetic susceptibility and indicates the accumulation of pathological iron, usually in perivascular macrophages, due to vasculopathy. As outlined in the Greenberg criteria,[1] it is crucial to distinguish between CMBs and other possible mimics, such as iron or calcium deposits, bones, or vessel flow voids. Microdissections, microaneurysms, and microcalcifications can mimic CMBs (false-positive microbleeds), but the latter can be differentiated using phase images. Substances with paramagnetic properties like hemosiderin, deoxyhemoglobin, and ferritin exhibit a dark appearance on magnitude images (SW) and appear bright on phase images when using a left-handed MRI system, compared to the surrounding brain tissue. Conversely, substances with diamagnetic properties, such as calcium, result in a negative shift and appear dark on phase images when using a left-handed MRI system. On a right-handed system, deoxygenated blood will display a dark (negative phase) appearance on phase images compared to the surrounding tissue, while calcium will appear bright (positive phase) because of its diamagnetic properties relative to the brain tissue. CMBs are becoming more common in normal aging. They are also frequently seen in various disorders such as cerebral amyloid angiopathy (CAA), hypertension microangiopathy, Alzheimer’s dementia, cerebral ischemia, chronic kidney disease, and traumatic brain injury. There are also less-common causes of CMBs, which include endocarditis, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, brain radiation therapy, posterior reversible encephalopathy syndrome, infective endocarditis, cocaine abuse, thrombotic thrombocytopenic purpura, intravascular lymphomatosis or proliferating angioendotheliomatosis, moyamoya disease, sickle cell anemia/β-thalassemia, and obstructive sleep apnea.[2] The cause and mechanism behind CMBs are not fully understood. However, hypertensive microangiopathy and CAA damage the blood–brain barrier and neurovascular unit, leading to blood leakage and hemosiderin deposition.[3] Hypertension may cause lipohyalinosis and fibrinolysis, which affects the deep penetrating arterioles, resulting in deep CMBs predominantly involving the basal ganglion brainstem and the thalamus. In contrast, in CAA, amyloid accumulation mainly occurs in the cortical and leptomeningeal arteries, leading to inflammation, oxidative stress, and apoptosis, resulting in CMBs predominantly in the cortex or lobar CMBs, rather than deep CMBs. Literature showed that more than 87% of CMBs in CAA are located strictly in the lobar region, predominantly in the posterior cortex of the brain, and that the remaining lesions are localized near the basal ganglion.[3] In this particular case, multiple unilateral CMBs were found in the frontal, parietal, occipital, and temporal lobes. In addition, a few deep CMBs were located in the basal ganglion of the right hemisphere. The lesion size of these mixed hemorrhages ranged from 3 to 8 mm. The number of microbleeds was more than 10, and there was associated grade 2 periventricular small vessel disease, favoring CAA. It is important to note that multiple cavernomas can also be CMBs, but their size can vary from 3 mm to 6 cm. Small vessel disease does not occur in cerebral cavernomas.[4] Unilateral presentation of CMBs due to multiple brain cavernomas and hypertensive microangiopathy has not been reported in the literature. However, there are few case reports of unilateral microbleeds caused by CAA.[5] According to the modified Boston criteria, a diagnosis of probable CAA can be made based on the patient’s age (above 55 years) and MRI findings showing multiple hemorrhages with cortical predominance with no other explanation and clinical evidence. CAA is usually asymptomatic, as in our case, and can cause a small vessel disease burden in older people. The lesions are primarily cortical CMBs rather than deep bleeds, and the brainstem is usually unaffected. Therefore, in our case, the diagnosis of unilateral probable CAA was unmasked after the patient experienced acute encephalopathy due to SIADH and systemic febrile illness. The limitation is that we could not perform a brain biopsy to confirm CAA. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.