Isolated Insular Stroke: An Interesting Report of Two Cases.

Dear Editor, The insula is a crucial anatomical structure, which is a pivotal center for the multitude of interconnecting brain networks.[1,2] The vascular supply is via the middle cerebral artery, which also supplies the neighboring regions of the insula.[3] Therefore it is not surprising that the symptoms of isolated insular stroke (IS) are frequently dominated by symptoms attributed to the adjacent structures, rather than those restricted to the insular cortex (IC) alone.[4,5] IS is a very rare, underreported entity with a heterogeneous and variable presentation. In a recent systematic review of 49 cases with first-ever stroke restricted to the insula, the authors concluded that a combination of vestibular-like, somatosensory, speech, or language disturbances in a patient should arouse the suspicion of an IS and appropriately investigated and managed.[6] Here we report two interesting cases of IS which posed a diagnostic challenge for us. The first case is a 38-year-old lady who presented to our hospital with an acute onset inability to speak, with a deviation of angle of mouth to left side, five days back. She had a history of a spontaneous abortion (at 12 weeks gestation), 15 days prior to the event. There was no history of fever, seizures, breathlessness, palpitation, headache, and vomiting. She had no significant past history. A general examination revealed a regular pulse of 88/min, blood pressure of 130/80 mm Hg. She had photosensitive malar rash and palatal ulcers. Examination of Central nervous system (CNS) revealed a Broca’s type aphasia and right upper motor neuron type facial palsy. Motor and sensory examinations were normal. NIHSS score was four. Examination of other systems was unremarkable. Laboratory investigations revealed the presence of lupus anticoagulant-normalized ratio 2.89 (normal <1.2), positive β2-glycoprotein1 IgM-54.92 Standard IgM Unit (SMU) (normal <20 SMU) and cardiolipin antibody IgM-44.84 IgM phospholipid Unit (MPL) (normal <12.5 MPL), positive direct Coombs test, Anti nuclear antibody (ANA) profile showed 4+speckled pattern, extractable nuclear antigen (ENA) profile showed RNP/Sm++, Sm++, dsDNA+, nucleosomes++. Complements-C3/C4 were reduced. Anti-dsDNA was >300 U/mL. Prothrombin time-international normalized ratio (PT-INR) and activated partial thromboplastin time (aPTT) were deranged. Hemogram revealed thrombocytopenia (100 × 109/L). Lipid profile, homocysteine, renal, and liver function tests were normal. Viral markers for HIV, hepatitis B/C, and Ebstein barr virus (EBV) were negative. The total 24-hour urinary protein was 560 mg/day. Electrocardiography showed normal sinus rhythm. Echocardiography showed mild pulmonary arterial hypertension. ESR was 50 mm 1st hour and CRP 3.1 mg/L (normal <6 mg/L). Computed tomography scan of the brain revealed acute left IC infarct [Figure 1a]. Carotid and vertebral doppler were normal. She was diagnosed with systemic lupus erythematosus (SLE) with secondary antiphospholipid syndrome (APS) and treated with prednisolone, warfarin, hydroxychloroquine, and statins. She recovered completely after three months of this presentation.Figure 1: (a) CT scan showing infarct over left isular cortex. (b) MRI Brain showing chronic infarct overt right insular cortexThe second case is a 60-year-old male who presented to the neurology clinic with complaints of acute loss of smell sensation and reduced taste sensation, five years back. He consulted an otolaryngologist for the above complaints and on the premise of an upper respiratory tract infection was administered multiple antibiotics and antihistaminics. On detailed questioning, he informed us that the development of symptoms was acute. He woke up on one fine morning and found he had lost his ability to smell and taste common household items like tooth paste, tea, food items, smell of incense sticks, soap, spices, and all his symptoms had remained almost static henceforth. He did not complain of any motor, sensory, gait, speech, visual deficits, altered sensorium, or seizures at that time. Detailed evaluation by an otolaryngologist did not reveal any anatomical abnormalities. On examination, he was unable to identify the smell of cloves, cinnamon, coffee, mouthwash, lemon, tooth paste, and soap through both nostrils. The gustatory test assessed four taste qualities, sweet, sour, salty, and bitter, using sugar, lemon, salt, and black coffee. He was able to vaguely recognize a sweet taste but had no appreciation of sour, salty, or bitter tastes. Sensory, motor, cerebellar, speech, and gait examinations were normal. Other system examinations were also normal. His blood pressure was 140/80 mmHg, pulse was 78/min, regular. Brain magnetic resonance imaging revealed chronic infarct in right IC [Figure 1b]. MR angiography was normal. Complete hemogram, homocysteine, blood sugar, lipid profile, liver and renal function tests, echocardiography, carotid and vertebral doppler were normal. His COVID reverse transcription polymerase chain reaction was also negative. Our first case is that of a lady with SLE and secondary APS who developed IS a fortnight after a spontaneous abortion. Neuropsychiatric disorders are important clinical manifestations of SLE and APS. The prevalence of stroke in SLE varies from 3% to 20%.[7] APS is an autoimmune disease characterized by recurrent thrombotic events, miscarriages, and thrombocytopenia, and it is associated with the persistent presence of antiphospholipid antibodies, which include anticardiolipin, lupus anticoagulant, and anti-beta 2-glycoprotein I (b2GPI). Secondary APS may occur in 25%–40% of SLE patients and can cause both ischemic and venous strokes.[8] Proinflammatory cytokines are released resulting in enhanced oxidative stress. In SLE, immune complex deposition on the vessel walls and later action of antibodies against them resulting in endothelial damage may lead to secondary vasculitis. The cumulative prevalence of stroke and Transient ischemic attack (TIA) in APS patients are 19.8 and 11.1%, respectively.[9] However, isolated IS has not been reported with SLE to date. Anticoagulation therapy is the first-line treatment in the prevention of stroke recurrence in patients with SLE with secondary APS.[7] Hydroxychloroquine controls the disease activity and has auxiliary benefits as an antithrombotic and antiatherosclerotic drug. Our second patient had developed hypogeusia and anosmia. The IC has been considered a primary gustatory cortex. It is believed that a gustotopic map exists in the mammalian IC, where specific neurons encode particular taste modalities.[10] IS can result in different forms of gustatory disturbances like ageusia, hypogeusia, parageusia, Gourmand syndrome (altered food preference).[6] Disturbance of taste sensation has been described in 12% of IS in literature. They are more severe after left IS (occurring in 19% of left IS versus 4% of right IS).[6] These reports suggest that the dominant anterior IC represents a crucial region for the perception of taste. Our patient developed gustatory disturbance after right-sided IS, which is very rare. His symptoms were static at three months follow-up. The functional prognosis of insular ischemic stroke appears to be excellent. There is a bidirectional relationship between the dorsal anterior insular (DAI) and the autonomic nervous system. The DAI is sensitive to the interoceptive sensations, like changes in the heart rate and blood pressure and also modulates and controls the autonomic nervous system thus maintaining sensory homeostasis (1) in our day-to-day life. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.