European Journal of Cardiovascular Medicine

Stroke in younger adults is less common than in older adults, accounting for approximately 10-15% of all strokes in adults aged 18 to 50 years.[1] The pathogenesis of stroke in younger adults requires additional consideration for several less common risk factors and etiologies. Fibromuscular dysplasia (FMD)[2]is a hyperplastic arterial disorder that predominantly affects medium-sized and small arteries, though it can also involve larger arteries. It occurs more frequently in females and typically targets the renal and carotid/vertebral arteries, but it can also affect coronary, mesenteric, iliac and subclavian arteries.

Young women with refractory hypertension and stroke are commonly seen but FMD does not exclusively affect young women. Conventional angiography studies[3] [4] CTA/MRA, often reveal a "string of beads" or "stack of coins" pattern, which is considered pathognomonic for FMD. These imaging findings, combined with clinical factors, lead to the diagnosis of FMD. Recognizing FMD as a possible underlying condition in young patients presenting with stroke is crucial, especially when standard risk factors are absent. This case highlights the importance of considering FMD in the differential diagnosis of young stroke [5] to ensure timely and appropriate management

Patient Information:

A 27-year-old female presented to the emergency department in an altered sensorium and unconscious state. She had a history of headache since the evening prior to presentation. There was no history of head injury, vomiting’s and convulsions. She reported similar episodes of headache in the past for which she had taken over the counter medication. Additionally, she was unable to move her left upper and lower limbs.

Clinical Findings:

• Vital Signs: Blood Pressure:190/100 mmHg, Pulse rate 74bpm
• Neurological Examination:
  • Power: Decreased in the left upper and lower limbs.
  • Tone: Decreased tone in affected limbs.
  • Reflexes: Decreased reflexes on the left side.
  • Plantar Response: Left side Extensor elicited

Diagnostic Evaluation

Upon admission, the patient underwent a series of diagnostic evaluations to determine the cause of her symptoms.

Blood investigations –

Hb-10.2gm/dl, WBC-8870/cm3 ,Urea-37mg/dl ,Creatinine-1.0 ,Sodium -138mEq/L, Potassium-3.8mEq/L,ESR and CRP normal. As a part of evaluation for stroke in young thrombophilia profile was done (beta 2 glycoprotein 1 IgG/Factor 5 gene mutation analysis/Lupus anticoagulant profile/homocysteine/antithrombin activity/Protein S functional assay/Protein C functional assay) all tested negative, Vasculitis profile and ANA profile were also negative.

Imaging Studies

Initial imaging, including a CT scan of the brain, suggested a large acute hematoma in the right capsulo-ganglionic region with hemorrhage extension to the lateral, 3rd, and 4th ventricles, and mild hydrocephalus. A left midline shift of 4.7 mm was noted[Fig.1]. Later, an MRI of the brain showed a large right basal ganglia acute/early subacute intracerebral hemorrhage (ICH), with associated intraventricular hemorrhage (IVH). Given the patient's young age and lack of conventional stroke risk factors, further diagnostic workup was undertaken to identify possible underlying etiologies.

Fig.1 : NCCT Brain scan: Acute hematoma in right capsulo-ganglionic region with hemorrhage in ventricles, mild hydrocephalus, 4.7 mm left midline shift.

Angiographic Studies

• MRA of Intracranial Arteries: Showed tight stenosis of the M1 segment of the right middle cerebral artery (MCA) just beyond its origin, with faint flow-related enhancement in distal branches [Fig.2].
• Color Duplex Doppler of Renal Arteries: Revealed a small left kidney with raised cortical echogenicity and altered cortico-medullary differentiation. Raised resistive index (RI) and Pulsatility index (PI) values of the left renal artery and arcuate artery were noted, along with turbulence and raised peak systolic velocity (PSV) in the right renal hilum.
• CT Renal Angiography: Showed a decreased size of the left kidney. The right kidney showed compensatory hypertrophy[Fig.3a,3b] The left main renal artery demonstrated severe grade narrowing (up to >95% luminal diameter stenosis) with a "string of beads" appearance extending to the left renal segmental arteries, which showed moderate grade stenosis (up to 60-70% diameter narrowing). The left main renal and segmental arteries also exhibited a "string of beads" appearance[Fig.4a,4b]. Associated left kidney parenchyma showed patches of hypodensity with no significant enhancement in all poles, indicating multifocal renal infarcts. Features suggested possible FMD with severe grade stenosis of the left renal artery and moderate to severe grade stenosis of the left segmental arteries, causing multifocal renal infarcts and decreased left renal size. The right kidney showed compensatory hypertrophy with mild stenosis (up to 40% diameter narrowing) of the right renal artery ostium but no significant stenosis of segmental, interlobar, or arcuate arteries.[Fig.5]

Fig. 2:MRA (Intracranial Arteries): Tight stenosis of right MCA M1 segment

Fig.3a Coronal View

Fig.3b Axial View

Fig.3: CT Renal Angiography: Showing  a decreased size of the left kidney, associated with parenchymal patchy hypodensity with no significant enhancement in all poles. The right kidney showing compensatory hypertrophy; Fig3a Coronal view, Fig3b Axial view

Fig.4a

Fig.4b

Fig.(4a,4b): CT Renal Angiography:

The left main renal (up to >95% luminal diameter stenosis) and segmental arteries(up to 60-70% diameter narrowing) exhibiting a "string of beads" appearance;Fig4a Coronal View,Fig4b Coronal View (Magnified)

Fig.5 CT Renal Angiography: The right kidney showing mild stenosis (up to 40% diameter narrowing) of the right renal artery ostium but no significant stenosis of segmental, interlobar or arcuate arteries.

Echocardiography

• Concentric left ventricular hypertrophy.
• No regional wall motion abnormality at rest.
• Good left ventricular (LV) systolic function with an ejection fraction (EF) of 62%.

Course of treatment:

Admitted with Hypertensive Emergency and ICH with no prior history of hypertension, all relevant investigations were done as mentioned above. Treated conservatively with Antihypertensives and Antiepileptics, Mannitol for short course and other supportive medications. Case reviewed with visiting cardiologist and neurologist. Patient later was planned for renal revascularization. Though unable to perform stent placement due to multilevel stenosis.

Management and Outcome

Acute Treatment

The acute management of the patient's hemorrhagic stroke involved stabilization and addressing the immediate neurological concerns. This included measures to control intracranial pressure and prevent further bleeding. Given her hypertensive status, antihypertensive therapy was initiated to manage blood pressure.

Long-Term Management

Focus was placed on the long-term management of the patient's condition to prevent recurrent strokes and other vascular events. This included:

• Blood Pressure Control: Ongoing antihypertensive therapy to manage renovascular hypertension.
• Monitoring: Regular follow-up appointments to monitor her vascular health and detect any additional vascular abnormalities. The patient was also educated on lifestyle modifications to manage her condition effectively.

Surgical intervention was planned, and she was referred for a vascular surgery opinion. However, due to multilevel stenosis, stent placement could not be performed.

Hypertensive Emergency and Intracerebral Hemorrhage (ICH) :

This case emphasizes the critical nature of hypertensive emergencies in young patients, with a 27-year-old female presenting with acute hypertensive crisis (BP 190/100 mmHg) and subsequent intracerebral and intraventricular hemorrhage. The acute neurological deficits highlighted the immediate need for  blood pressure management to prevent further neurological damage.

Fibromuscular Dysplasia (FMD) and Secondary Hypertension[6]:

The characteristic "string of beads" appearance on Duplex ultrasound and CT Renal Angiography indicated fibromuscular dysplasia (FMD), a condition causing severe arterial stenosis and resistant hypertension. FMD, a non-atherosclerotic vascular disease, is frequently seen in young females and is often underdiagnosed. It accounts for 4-6% prevalence in renal arteries and 0.3-3% in cervico-encephalic arteries, though true prevalence might be higher due to asymptomatic cases [7]. FMD can lead to stenosis, dissection, thrombosis, aneurysm and even stroke in young.

Patients with FMD often present with non-specific symptoms such as headaches, dizziness, and neck pain. In this case, the patient’s presentation included altered sensorium, weakness in the limbs, and a history of headaches, which are consistent with both hypertensive encephalopathy [8] and FMD.

Comprehensive Diagnostic Evaluation [9]:The patient underwent thorough diagnostic testing, including blood investigations, CT and MRI brain scans, MRA, Doppler, and CT Renal Angiography. The exclusion of thrombophilia /vasculitis / hypercoagulable states, essential to focus on the underlying vascular pathology.

MultidisciplinaryManagement Approach[10]:The management involved a multidisciplinary team, including physicians, cardiologists and neurologists, who employed antihypertensives, antiepileptics, and osmotic diuretic to stabilize the patient. The involvement of multiple specialties ensured comprehensive care addressing both acute and underlying conditions.

Prognosis and Follow-Up : Long-term outcomes for patients with hypertensive emergencies and ICH depend on early intervention, ongoing blood pressure control, and management of underlying conditions like FMD. Regular follow-ups with blood pressure monitoring, renal function assessments, and repeat imaging are crucial to prevent recurrence and ensure optimal recovery. Plan for renal revascularization if needed.[11]

Younger population, especially females with incidence of strokes at young age are found to have renal artery stenosis due to fibromuscular hyperplasia and is the most common cause of secondary hypertension in these patients[12]

In summary, this case underscores the need for heightened awareness and early detection of secondary causes of hypertension such as FMD in young patients. A thorough diagnostic approach, prompt management, and multidisciplinary care are key to improving outcomes in such complex cases. Also, the importance of considering FMD in the differential diagnosis of young stroke patients, thorough evaluation of young stroke patient, especially in the absence of traditional risk factors. Regular follow-up is essential to monitor and manage potential complications, thereby preventing further catastrophic events.

This case highlights the importance of considering fibromuscular dysplasia in the differential diagnosis of hemorrhagic stroke in young adults, particularly in the absence of traditional risk factors. Early recognition and appropriate management of FMD can lead to favorable long-term outcomes and improve the patient's quality of life. Thorough investigation and a high index of clinical suspicion are essential in diagnosing and managing such conditions.

1. Christopher A. Stack and John W. Cole The Clinical Approach to Stroke in Young Adult
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11. A Rare Case of Focal Renal Fibromuscular Dysplasia Treated With Angioplasty: A Case Report Abdulqader Al-Falahi et al. Vasc Endovascular Surg. 2024 Feb.
12. Fibromuscular dysplasia: an uncommon cause of secondary hypertensionL Michael Prisant et al. J Clin Hypertens (Greenwich). 2006 Dec.