Subarachnoid hemorrhage (SAH) is a rare but life-threatening complication in patient undergoing hemodialysis (HD) and it is associated with a high mortality rate if not promptly diagnosed and treated. SAH is characterized by bleeding into the subarachnoid space between the arachnoid membrane and the pia mater¹. SAH has been reported to occur more frequently in patients undergoing HD than in the general population².Familial Mediterranean Fever (FMF) is an autosomal recessive inheritance pattern, characterized by recurring episodes of fever and serositis, which predominantly impact individuals with Mediterranean heritage. FMF has been associated with several systemic manifestations, including vasculitis, arthritis, and amyloidosis. In addition, FMF, an autoinflammatory disease, has been implicated as a potential risk factor for the development of SAH. Neurological complications are rare in FMF, but acute stroke has been reported in some cases. However, the exact mechanisms underlying the increased risk of SAH in HD patients with FMF remain unclear. Several mechanisms have been proposed to explain the association between FMF and SAH, including cerebral vasculitis, arterial wall inflammation, and endothelial dysfunction. This case report presents a rare case of spontaneous, nona-neurysmal, nontraumatic, SAH in a normotensive young HD patient with FMF and discusses the potential contributing factors and management strategies.

Following one day after his HD session, a 28-year-old male patient with a medical history of FMF, arrived at the emergency department experiencing a sudden onset of severe headache and vomiting. The patient had been undergoing HD three time in a week for the past 3 years due secondary end-stage renal disease (ESRD) to FMF. He had a history of recurrent attacks of FMF for the past 10 years, which were not well-controlled with colchicine therapy. The patient had no history of hypertension or other comorbidities. On examination, the patient was alert and oriented with no focal neurological deficits. His blood pressure was 140/80 mmHg. In the examinations of the patient, PT, aPTT, INR, thrombocyte and bleeding time were within the normal range. The non-contrast computed tomography (NCCT) showed no evidence of aneurysms or vascular malformations (Figure 1, 2). CT brain showed SAH (Figure 2).

Figure 1: Non-contrast computerized tomography brain showing subarachnoid hemorrhage in a young Hemodialysis patient (black arrow).

Figure 2: Repeat non-contrast computerized tomography brain showed Subarachnoid hemorrhage (black arrow).

The patient did not report any incidents of head trauma or falling, nor had a bleeding diathesis or intracerebral bleed in his medical history. Additionally, following consultation with a neurosurgeon, nimodipine was initiated, while Mannitol, Dexamethasone, and other "anti-edema" treatments were not administered.

The patient was admitted to the intensive care unit for close monitoring and supportive care. He was continued on nimodipine and started antiepileptic therapy. The patient's HD was continued without heparin and he remained hemodynamically non-stable throughout his hospitalization. The patient passed away after 20 days of hospitalization in intensive care unit.

SAH is a rare but serious complication that can occur in patients undergoing HD. SAH is defined as bleeding into the subarachnoid space, which is the area between the arachnoid mater and the pia mater that covers the brain. In HD patients, SAH is associated with higher morbidity and mortality rates compared to the general population³. The exact etiology of SAH in HD patients is not fully understood, but it is believed to be multifactorial in nature. Research conducted on the general public has demonstrated that the likelihood of developing SAH is higher in females, individuals with hypertension, smokers, those who abuse alcohol, and people of non-white racial backgrounds.^4-6.

Approximately 85% of all cases of SAH arise from the rupture of saccular aneurysms located at the base of the brain. Non-aneurysmal perimesencephalic hemorrhages constitute 10% of SAH cases, with the remaining 5% stemming from other uncommon causes. Risk factors for SAH include genetic predisposition and modifiable factors such as smoking, hypertension, and excessive alcohol consumption. A significant risk factor is having a family history of SAH, as first-degree relatives have a 3 to 7 times higher risk of experiencing it. Certain inherited disorders, such as Autosomal Dominant Polycystic Kidney Disease (ADPKD), are linked to a higher susceptibility of SAH. Roughly 2% of SAH patients have been diagnosed with ADPKD. While other inherited conditions, such as Ehlers-Danlos Disease IV, neurofibromatosis type 1, and Marfan's Syndrome, have also been linked to SAH, they are less commonly found in affected patients. The rupture of aneurysms may be triggered by a sudden increase in intramural arterial pressure. Activities that can cause bleeding, such as physical exercise, sexual intercourse, and straining, have been reported in up to 20% of cases. Individuals receiving maintenance dialysis have an elevated likelihood of experiencing bleeding compared to the overall populace. Earlier studies have indicated that this group is especially susceptible to gastrointestinal bleeding and subdural hematomas.^7,8. The heightened risk of bleeding observed in patients receiving maintenance dialysis is believed to result from defects in the coagulation pathway and the administration of anticoagulation treatment during dialysis. Studies have reported an increased incidence of SAH in HD patients, with a prevalence of up to 6.8% in some populations⁹. A retrospective study analyzing the incidence of SAH in HD patients found that the risk of SAH was higher in HD patients compared to non-HD patients, with a standardized incidence ratio of 4.4^9,10. Another study found that HD patients with SAH had a higher mortality rate and worse outcomes compared to non-HD patients with SAH^9,11. Cerebrovascular accidents such as acute ischemic stroke, subarachnoid hemorrhage and hematoma are not common in FMF patients. In a study of 23 FMF patients, a total of 35 acute stroke events were observed. Acute ischemic stroke attack was observed in 19 of these patients, transient ischemic attack in 3 and parietal hematoma in 1 patient. Subarachnoid hemorrhage was not seen ¹².

The management of SAH in HD patients can be challenging, with surgical intervention being the mainstay of treatment. However, these patients may be at increased risk of complications such as cerebral vasospasm and rebleeding. Therefore, early diagnosis and appropriate management are crucial in improving patient outcomes.

The exact etiology of SAH in HD patients remains unclear, but it is thought to be multifactorial in nature, and further studies are needed to better understand the underlying mechanisms of this complication. In this case report, we present the case of a 28-year-old male patient with FMF who developed SAH during his HD session. Despite prompt diagnosisand supportive care, the patient passed away after 20 days of hospitalization. In this publication, we aimed to present a case of SAH in a patient who undergoing HD due to ESRD secondary to secondary FMF. We did not come across any publications with a history of FMF in previous studies or case reports. In this aspect, the case we presented has the feature of being the first. We thought that the underlying reason for this may be that FMF is an autoinflammatory condition and may have triggered SAH in our patient. We wanted to emphasize that researchers should keep in mind that HD patients with an autoinflammatory disease such as vasculitis or FMF are at risk of SAH.

The etiology of SAH in our patient remains unclear. Further studies are needed to elucidate the underlying mechanisms of SAH in HD patients with FMF. Prompt diagnosis and appropriate management are crucial in improving the outcome of such patients.