Rare cause of stroke in young: Iron deficiency anemia and diabetic ketoacidosis.

Iron deficiency anemia (IDA) is a well-known cause of stroke in children, but its association is relatively rare in adults. We describe a case of 36-year-old woman, a known diabetes mellitus, who presented with recurrent vomiting, headache, and altered sensorium. Investigations revealed severe iron deficiency anemia, thrombocytosis, and ketoacidosis. Magnetic resonance imaging suggested acute infarct of B/L parieto-occipito-temporo-cerebellar region. Patient was worked up for possible causes of stroke in young. She underwent computed tomography angiography of the brain, echocardiogram, and screening for thrombophilia disorders. This, however, did not demonstrate a clear etiology and there were no other evidences of diabetic angiopathy. Some previously published case reports have suggested IDA as a potential cause of ischemic stroke; it is possible that the stroke in this young woman was attributable to severe IDA. Whether cerebrovascular accident has led to diabetic ketoacidosis or vice versa is a topic of discussion which needs further studies. Moreover, such catastrophes could be prevented by early diagnosis and timely management through involvement of primary care physicians.

Introduction

Stroke in young is a relatively rare entity than stroke in elderly with variant etiologies. It is very important to identify the cause for definite management and prevention of recurrence of ischemic stroke. Anemia is not well recognized as a potential cause of stroke in young adults, although such association has been reported in case reports and case series, particularly in pediatric population.[1] However, the occurrence in adults has been reported only in few case reports[23] with majority showing thrombosis, secondary to IDA with thrombocytosis, as the cause of ischemic stroke.[2] Without thrombosis how IDA can cause stroke is not being documented. Diabetic ketoacidosis (DKA) has also been reported to be a risk factor for occurrence of stroke in children and young, and stroke can also precipitate DKA. Let us assume for this case study: DKA is a risk factor for young stroke. Thereby we describe a more interesting case of co-existence of two rare possible causes (IDA and DKA) of ischemic young stroke.

Case Presentation

A 36-year-old woman presented to the Emergency Department with complaints of 2-day history of nonprojectile vomiting and severe headache followed by altered sensorium since last 8 h without any history of seizure. She had history of progressively increasing generalized weakness and shortness of breath on exertion for the last 2 months. Her past medical history was remarkable for menorrhagia due to uterine fibroid diagnosed 1 year back. She was a known diabetic for the last 8 years and was on oral hypoglycemic drugs (gliclazide + metformin + gliptins) with variable glycemic. There was no history of oral contraceptive use. Her family history was negative for any premature cardiovascular, hematological, or neurological disorder. On examination she was dehydrated and having severe pallor. She had tachycardia with hypovolemic pulse, blood pressure 90/60 mm Hg, Glasgow coma score (GCS)-10 (E3V2M5), normal pupils, and extensor bilateral planters. Her cardiovascular, respiratory, gastrointestinal, and lymphoreticular system examination was unremarkable. Based on the history and clinical examination, we kept the possibilities of (1) metabolic encephalopathy and (2) cerebrovascular accident (CVA) with severe anemia. Her initial investigations were suggestive of diabetic ketoacidosis (random blood sugar: 484 mg/dL, pH: 7.203, HCo3: 11.8 mmol/L, Na: 126 mmol/L, K: 3.7 mmol/L, urine ketones +++) and was managed with standard protocols, i.e. intravenous fluid, insulin, and electrolyte management. Her noncontrast computed tomography (CT) brain showed bilateral parieto-occipito-temporal infarction. Hence the diagnosis of acute ischemic stroke with DKA and severe anemia was made. The possible causes were thought from the most common to the least common, i.e. cardioembolic, blood vessels abnormalities, thrombophilia with other hematologic disorders, connective tissue-associated disorders, and tried to rule out them one by one.

Further laboratory analysis showed hemoglobin 4.6 g/dL, hematocrit 20%, mean corpuscular volume 70.7 fL, mean corpuscular hemoglobin 16.3 pg, and ferritin 2.7 ng/mL (normal range 10–291 ng/mL), which were all below normal limits with increased WBC counts (13,400 cells/cumm), red cell distribution width (29.9). Peripheral blood smear displayed neutrophilic leukocytosis with microcytic hypochromic anemia. She also had thrombocytosis with a platelet count of 912,000 lakhs/cumm. Her lipid panel was normal. The other parameters including liver and kidney function tests were within normal limits. MRI brain confirmed acute infarct in bilateral parieto-occipito-temporal regions, capsulothalamic regions, and cerebellar hemispheres with hemorrhagic transformations. CT angiography brain revealed no abnormalities.

Other possible etiological factors for stroke were performed, i.e. ECG, two-dimensional echocardiography, vitamin B12, homocysteine, coagulation profile, antinuclear antibody, and collagen profile, which came out to be normal.

During her hospital stay she received standard management of IDA, DKA, and ischemic stroke, following which she symptomatically improved with GCS-15/15, and started taking orally. She was transfused with three units packed RBCs and 1 g ferric carboxymaltose along with other supportive management. Her laboratory parameters improved and on discharge had hemoglobin 10 g/dL.

Discussion

This case is unique because of events that led to stroke in young: an interesting coalition between IDA and DKA. The association between IDA and stroke has been better defined in children than adults through three possible mechanisms: venous sinus thrombosis from reactive thrombocytosis, arterial cerebral infarctions with possible thrombus formation, or severe hypoxia and severe anemia causing reversible neurologic deficits in the setting of atherosclerotic cardiovascular disease. Normal CT angiography of brain with bilateral hemispheric involvement support our hypothesis of hypoxia-associated cerebral vasoconstriction secondary to severe IDA as mechanism of stroke in our patient.

DKA associated with thrombotic risks and cerebral edema might predispose to stroke.[4] In addition, the reverse is also true that CVA is a significant and well-known risk factor for DKA (prevalence rate 0–7%).[56] However, a majority of studies have suggested that the human body is able to tolerate a certain anemic state and CVA does not occur in all patients with severe IDA, particularly in adults where auto-circulation is good enough compared to the children. That is why (although DKA is rarely associated with stroke in adults) it seems DKA as the second etiological factor for the development of CVA in our case. The precipitating factor of DKA seems to be poor glycemic-controlled status on oral hypoglycemic agents.

The patient had very rapid improvement in her clinical and laboratory parameters with no new neurological deficits occurring after the resolution of IDA, thus suggesting a positive influence of aggressive management for IDA on stroke outcome, which was in accordance with the study results of Huang et al.[7]

Both IDA and diabetes mellitus (DM) are two important treatable health issues in community with high prevalence rate. Despite having established guidelines for management, these are very often overlooked or mismanaged with poor compliance of patients contributing to poor treatment outcome. Our patient had IDA due to chronic blood loss, which along with poorly controlled DM led to devastating neurological complications which was preventable through early diagnosis and treatment.

Family physician and primary care provider often being first contact between patient and health care facilities should be aware of such rare complications of commonly prevalent diseases occurring because of delayed management and their threshold to investigate such cases with subtle presentation should be low. They play important role in prevention and management such as early diagnosis and treatment of IDA, early referral to specialist care whenever needed, i.e. cause-specific management of IDA, uncontrolled DM, monitoring of compliance of patient and community health education, and increasing health awareness.

Learning points:

IDA is a preventable and treatable cause of stroke in young especially females.

Along with DKA, IDA can present as stroke even without thrombosis.

Timely proper management of IDA and DKA can prevent permanent neurological complications.

Strengthening primary care might help preventing devastating rare complications of commonly treatable diseases.

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.