Balint syndrome is a disorder of inaccurate visually guided saccades, optic ataxia, and simultanagnosia that typically results from bilateral parieto-occipital lesions. Visual perception disturbances in the posterior reversible encephalopathy syndrome (PRES) include hemianopia, visual neglect, and cerebral blindness, but Balint syndrome had not been recognized. We report Balint syndrome associated with PRES in a 37-year-old woman with acute hypertension and systemic lupus erythematosus. Balint syndrome can be an initial presentation of PRES.
Division of Neurology and Department of Ophthalmology and Vision Sciences, University Health Network, University of Toronto, Toronto, Ontario, Canada.
The authors report no conflicts of interest.
Address correspondence to Sunil Kumar, FRCS, MS, University Health Network W5-815 TWH, 399 Bathurst Street, Toronto M5T 2S8, Canada; Email: email@example.com
Posterior reversible encephalopathy syndrome (PRES) is characterized by seizures, headache, and visual symptoms with hyperintense signals due to vasogenic edema predominantly involving the parieto-occipital region on T2 or FLAIR sequence of MRI (1,2). The central nervous system manifestations of systemic lupus erythematosus (SLE) are diverse (3). However, PRES associated with SLE has seldom been reported (4).
Inaccuracy of visually guided saccades, optic ataxia, and simultanagnosia, the cardinal features of Balint syndrome, usually occurs with bilateral parieto-occipital lesions (5). We report Balint syndrome as the initial presentation of PRES in a patient with SLE.
A 37-year-old woman complained of abdominal pain, nausea, vomiting, alopecia, malar rash, and arthritis. Her serum was positive for anti-double-stranded DNA and anticardiolipin antibodies. SLE was diagnosed and treated with intravenous methylprednisolone. Her blood pressure was elevated, and lupus nephritis was presumed responsible, but serum creatinine was normal (64 μmol/L; normal range, 50-90 μmol/L), and renal biopsy was not performed.
Two weeks after initial presentation, she rapidly developed bilateral impairment of vision. Her medical history was unremarkable. Physical examination was remarkable for a blood pressure of 190/150 mm Hg. The mini mental status examination was normal. Her visual acuity was difficult to assess because she made erroneous saccades toward optotypes but was at least 20/400 in each eye. She was able to count fingers in the left hemifield of each eye but perceived only hand movement in the right hemifields. Pupils were 3 mm and reacted normally to light. Ductions were full and pursuit was saccadic. Although the patient had full range of volitional saccades to directional commands, she could not make visually guided saccades to small or large objects in any direction. That is, saccades were generated in directions that grossly missed fixation of visual objects presented in portions of the visual fields where they could be seen. Hand movements were dysmetric when the patient attempted to grasp a viewed object but accurate toward her own body parts. She was unable to recognize more than 1 item at a time when presented with the Cookie Theft Picture (6). Dilated fundus examination was normal. Three days later, automated visual field testing showed a right inferior homonymous quadrantanopia. Visual evoked potentials were normal. Epileptiform changes emanating from the occipital lobes were recorded on electroencephalogram. MRI on the day of admission to hospital showed extensive FLAIR hyperintensity within the parietal, occipital, and frontal lobes. Diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) demonstrated restricted diffusion in some of the involved areas (Fig. 1). Magnetic resonance venography was normal.
Hypertension was treated with angiotensin-converting enzyme inhibitors, and prednisone, mycophenolic acid, and hydroxychloroquine were given to treat SLE. Optic ataxia resolved 6 days after the initiation of treatment. Simultanagnosia and impaired visually guided saccades resolved at 3-month follow-up. Six months following initial presentation, the patient's vision improved to 20/80 in each eye, and the right inferior homonymous quadrantanopia resolved. Brain MRI six months following initial presentation showed a significant improvement. FLAIR hyperintense signals in the parietal lobes had resolved, while areas of increased signals in the occipital lobes were consistent with residual gliosis (Fig. 2).
The term Balint syndrome was proposed in 1954 (7) to denote the clinical features of a patient reported by Rudolf Balint in 1907 (8). These included inaccurate visually guided saccades, optic ataxia, and simultanagnosia. As in our case, visual field defects, though not an element of Balint syndrome, have also been reported (9). Bilateral parieto-occipital ischemia due to arterial occlusive disease (10,11) or acute hypotension (12) is the dominant cause of Balint syndrome (Table 1).
Patients with Balint syndrome are unable to make accurate voluntary or reflexive saccades to visual targets, despite an unrestricted range of eye movements. These inaccurate saccades, described as “psychic paralysis of gaze” by Balint are sometimes incorrectly referred to as ocular motor apraxia (17). Optic ataxia consisting of inaccurate visually guided limb movements, despite intact motor function, is a cardinal feature of Balint syndrome (18). Patients with Balint syndrome exhibit defective perception of objects in the visual field, except for isolated objects of attention. If attention is shifted from the previously appreciated object, regardless of size, it is not perceived (18). Patients can describe only a series of single objects and are unable to describe an entire scene. Balint (8) described this focal attention as “fatigability of attention,” which is now termed “simultanagnosia.” Our patient exhibited all these features.
Reversible white matter edema presenting with headache, decreased alertness, altered mental functioning, seizures, and abnormalities of visual perception was reported as the reversible posterior leukoencephalopathy syndrome (RPLS) (1). It became apparent that RPLS was a misnomer as it is not always reversible, may extend beyond the posterior region of brain, and can involve both white and gray matter. Stott et al (19) proposed an alternate designation of PRES. Vision perception disturbances include hemianopia, visual neglect, and cerebral blindness (20), but Balint syndrome had not been recognized in PRES.
PRES may occur in numerous clinical settings (Table 2), although severe hypertension is a major predisposing factor (27). Recurrence has been reported in 4% of patients (28).
Cerebral edema in PRES predominates in the parieto-occipital region but is often more widespread involving the frontal lobe, temporo-occipital junction, and cerebellum (29). Isolated edema of the brainstem or basal ganglia has been reported in atypical PRES (29). This edema commonly involves the border zone of cerebral arterial territories. Bilateral symmetrical edema mainly involving the subcortical white matter is a typical MRI finding. Increased apparent diffusion coefficients (ADCs) accompanied by anisotropy loss in the involved regions on DWI and diffusion-tensor sequences suggest reversible vasogenic edema as an underlying pathophysiology (30). The absence of abnormalities on DWI predicts a favorable outcome. Most often DWI and ADC changes are consistent with vasogenic edema, which is also associated with a favorable prognosis. However, increased signal on DWI accompanied by a reduced ADC signal indicates cytotoxicity and cell loss from ischemic necrosis (4). Focal areas of restricted diffusion representing infarction or tissue injury with cytotoxic edema are uncommon (11%-26%) in PRES (31). Such tissue injury may lead to gliosis and result in permanent hyperintense signal alterations on FLAIR (32). Nevertheless, DWI, even with ADC maps, is limited in precisely predicting the clinical course of PRES (33).
Possible mechanisms of PRES are controversial. A hypertension-hyperperfusion theory holds that hypertension overwhelms the autoregulatory capability of brain vasculature leading to capillary bed injury, vasogenic edema, and hyperperfusion (34). This theory does not explain PRES in normotensive patients, the negative correlation between severity of hypertension and PRES, or drug-induced PRES. Second theory deals with activation of T cells, considered to play an important role in the development of PRES in association with toxemia of pregnancy, allogenic bone marrow transplant, solid organ transplant, infection, autoimmune diseases, and chemotherapy. Cytokines released by activated T cells trigger activation, augmented surface marker expression, and diffuse injury of endothelial cells. Cytokine-induced leukocytes adherence and tissue migration (trafficking) causes microcirculatory dysfunction. Endothelial damage and leukocyte trafficking seem to play an important role in cerebral hypoperfusion and vasogenic brain edema in PRES. Depletion of endothelium-derived nitric oxide, leading to platelets aggregation and vasoconstriction, is postulated to play an important role in pathophysiology of PRES (35). Biopsy obtained during the acute stage of PRES demonstrates vasogenic edema, reactive astrocytes, and microglia and evidence of endothelial activation (36).
The role of SLE in the pathogenesis of PRES is often unclear. Often multiple factors associated with PRES are found in the SLE patient population, including hypertension, nephritis, and immunosuppressive drugs. In our patient, the relative roles of acute hypertension and cerebral SLE in the pathogenesis are not known. Either of both may have been responsible. The MRI appearance of PRES in SLE does not differ from PRES due to other causes (37).
To our knowledge, Balint syndrome has not been previously described in association with PRES. Fortunately, the outcome of this syndrome is typically favorable (38), as illustrated by the rapid resolution of Balint syndrome in our patient.
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