Neuroretinitis with abnormal brain imaging in Ask-Upmark kidney: A novel case report.

We report a 13-year-old female patient having vertigo and visual blurring since 2 weeks with blood pressure being 180/106 mmHg. Fundus examination showed optic disc edema with macular star. After ruling out infective causes, idiopathic neuroretinitis was diagnosed. Her brain magnetic resonance imaging (MRI) scan revealed three periventricular morphologically multiple sclerosis (MS)-like white matter lesions. Renal ultrasound and renal arteriogram showed a shrunken left kidney, small non-stenotic left renal artery and reduced vessels in upper pole of left kidney, consistent with Ask-Upmark kidney (AUK). Her symptoms improved with antihypertensive drugs. Follow-up MRI at 1 year revealed no interval change, while fundus had normalized. Neuroretinitis typically has normal brain MRI and rules out MS. However, our patient having AUK-induced hypertension had neuroretinitis and MS-like brain lesions and did not fulfill diagnostic criteria for MS. Thus we postulate that MS-like lesions can be part of neuroretinitis, especially in hypertensive patients.

Introduction

Neuroretinitis is characterized by optic disc edema and retinal exudates forming a macular star. It may be monophasic or recurring, infectious or idiopathic.[12] Though classically it is described with a normal brain MRI, our patient presented with a few hyperintense lesions. Also, our patient was suffering from hypertension at a young age due to an extremely rare disease, called Ask-Upmark Kidney (AUK).[3] We would like to throw light on the same, and present a short review of literature on this ‘curable’ form of hypertension.

Case Report

A 13-year-old female patient was referred to our hospital with a suspected diagnosis of multiple sclerosis. At the time of presentation to the previous hospital, she had complaints of acute onset blurring of vision with eye pain of 2-weeks duration. Along with, she also complained of vertigo, and moderate intensity continuous heaviness type of occipital headache of 6 -weeks duration. There was no history of fever and no history of contact with cats. Clinical notes of the previous hospital mentioned bilateral papilloedema, while rest examination was noted as normal. On admission to our hospital, her blood pressure was noted as 180/106 mm Hg and pulse rate 84/minute. All peripheral pulses were well palpable and no significant difference was noted in her blood pressure in other limbs. No lymphadenopathy was noted. On her routine ophthalmological examination, her visual acuity was 6/9 in both eyes. Fundus examination showed optic disc edema and macular star typical of neuroretinitis [Figures 1 and 2]. Laboratory studies including complete blood count, sedimentation rate, electrolytes, liver, and renal function tests, Human Immunodeficiency Virus- Enzyme linked immunosorbent assay (HIV-ELISA) and urine microscopy were normal. Her brain magnetic resonance imaging (MRI) scan revealed three periventricular smooth oval shaped white matter lesions. These lesions were hypointense on T1W images and hyperintense onT2W and FLAIR and non-contrast enhancing [Figure 3]. To rule out renal cause of young hypertension, an ultra-sonogram of kidneys was done, which showed left kidney 3.5 cm smaller than the right kidney. Renal Doppler revealed reduced flow in the lower pole of the left kidney. Renoangiogram showed small non-stenotic left renal artery with reduced vessels in upper pole of left kidney [Figure 4]. These findings were consistent with the diagnosis of AUK. Neurological diagnosis of neuroretinitis was kept based on fundus findings. Investigations in view of MRI brain findings were done to rule out multiple sclerosis (MS), of which Cerebrospinal fluid (CSF) analysis and MRI of whole spine were normal. Investigations for infective causes of neuroretinitis including serum and CSF VDRL and serological test for Bartonella henselae and Lyme's disease were negative. Antinuclear antibody and anti-neutrophil cytoplasmic antibodies were negative. Thus a diagnosis of idiopathic neuroretinitis was made. In view of hypertension secondary to AUK, patient was advised nephrectomy but due to her refusal for surgery, she was treated conservatively. During last 3 years the patient's blood pressure has been well controlled with tablet losartan 50 mg and hydrochlorothiazide 12.5 mg once a day. One year after control of hypertension, her fundus examination was normal and repeat MRI showed no new lesions and static old ones.

Figure 1

Left eye optic fundus photograph showing disc edema with macular star

Figure 2

Right eye optic fundus photograph showing disc edema with macular star and hemorrhages

Figure 3

MRI brain coronal fluid attenuated inversion recovery image showing periventricular hyperintense lesions

Figure 4

Renal angiogram showing small non-stenotic left renal artery with reduced vessels in upper pole of left kidney

Neuroretinitis is an inflammatory disorder characterized by macular exudates in star pattern with optic disc edema. Before labeling neuroretinitis as idiopathic, infectious etiologies like Bartonella, lyme's disease, syphilis, and toxoplasmosis should be ruled out.[12] Pathophysiology of neuroretinitis involves increased permeability of disc vasculature and secondary leakage of lipoproteinaceous material into the macula.[14] Hypertension causes disc edema, cotton-wool spots, exudates and retinal hemorrhages in optic fundii. Malignant hypertension can cause hard exudates in star pattern. AUK is a rare form of rennin-dependant hypertension first described by Ask-Upmark in a young female in 1929.[3] Initially considered to be a congenital anomaly, it is now considered likely to be an acquired entity. Recurrent urinary reflux and associated infections cause parenchymal pressure, which in the long term leads to segmental atrophy and a shrunken kidney, characteristic of AUK. The disease can be unilateral or bilateral, focal or diffuse. The involved hypoplastic segments have cystic and dilated tubules filled with colloid like substance, giving the characteristic “thyroid like” appearance.[5] These hypoplastic segments have no glomeruli, a point differentiating it from chronic pyelonephritis. Return of blood pressure to normal following nephrectomy suggests that the hypertension is renin dependant.[6] Subcortical and periventricular white-matter areas in brain have a marginal blood supply, making them most vulnerable to any decrease in blood supply.[7] In hypertensive patients, due to loss of cerebral autoregulation of blood pressure, they are prone to ischemic injury during episodes of relatively lower cerebral perfusion, even at levels considered normal for normotensive patients.[8] Chronic hypertension causes hyalinization, tortuosity, elongation and narrowing of the arterioles, leading to decreased blood flow and ischemia.[79]

Thus, our patient of AUK-induced hypertension had presented with clinical and fundus examination findings suggestive of neuroretinitis and brain MRI revealing location-wise MS-like lesions. However, neither did the patient's history, nor the MRI or other investigations suggest MS. Also, the MRI lesions did not fulfill the diagnostic criteria for MS. Till date, the existing knowledge is that neuroretinitis is associated with normal MRI and it effectively rules out MS. However, in our patient we found this rare combination of both. We would like to put forward that neuroretinitis can be associated with brain lesions, and both could possibly be a part of hypertension secondary to AUK. However, hypertension -related white matter hyperintensities are more diffusely distributed and more likely at an advanced age, compared to our patient who was in her second decade which goes against this hypothesis. Thus, there may be other factors yet not known along with hypertension which could explain the pathophysiology behind these lesions. Further studies of neuroretinitis in AUK patients are needed to reach to a conclusion. Since AUK is a curable entity its accurate diagnosis in a patient with neuroretinitis or MS-like lesions marks a major impact on patient's outcome. Also, none of the previously reported cases of AUK mention neuroretinitis as a part of the clinical profile.