Walsh, Ryan D. MD; Floyd, Jessica P. MD; Eidelman, Benjamin H. MD, PhD; Barrett, Kevin M. MD, MSc
Department of Neurology (RDW), University of Pennsylvania, Philadelphia, Pennsylvania; and Department of Neurology (JPF, BHE, KMB), Mayo Clinic Florida, Jacksonville, Florida.
Address correspondence to Ryan D. Walsh, MD, University of Pennsylvania, Department of Neurology, 3W Gates Building, 3400 Spruce Street, Philadelphia, PA 19104; E-mail: email@example.com
The authors report no conflicts of interest.
Bálint syndrome is a combination of simultagnosia, optic ataxia, and ocular apraxia (1). Simultagnosia is the inability to interpret a complex scene despite being able to perceive its individual elements (2). Optic ataxia describes misreaching under visual guidance despite normal limb strength and position sense resulting from dysfunction of visual connections to the motor cortex (1,2). Ocular apraxia manifests as difficulty with the initiation of voluntary saccades, while reflex saccades remain intact (2). Bálint syndrome typically results from pathology affecting bilateral parietal-occipital regions (3). Multiple etiologies have been described, including cerebrovascular disease, trauma, tumor, prion disease, HIV, leukoencephalopathies, and degenerative conditions, such as Alzheimer disease and posterior cortical atrophy (2,4). When the syndrome is a result of cerebrovascular disease, watershed infarction related to systemic hypotension is the usual cause (2). Vasculopathies, including central nervous system (CNS) vasculitis, have been implicated as well (1,5).
Reversible cerebral vasoconstriction syndrome (RCVS) describes a group of vasculopathic disorders characterized by reversible segmental vasoconstriction involving arteries of the circle of Willis and their branches (6). These disorders include thunderclap headache with vasoconstriction, benign angiopathy of the CNS, Call-Fleming syndrome, postpartum angiopathy, and drug-induced vasospasm. We describe a patient with RCVS who developed Bálint syndrome and visual allochiria, a unique symptom in which visual stimuli are transposed to the opposite side of visual space.
A 67-year-old right-handed woman presented to an outside facility complaining of severe right retro-orbital headache with abrupt onset while straining on the toilet. Medical history was significant for hypertension with a prior episode of symptomatic hypertension requiring hospitalization, hyperlipidemia, diabetes, and renal artery stenosis with prior stent placement. Medications included aspirin, atenolol, and irbesartan. Family history included ischemic stroke in her father. She was employed as a nurse, consumed 2 alcoholic beverages daily, and had a remote smoking history. Blood pressure on presentation was 155/86 mm Hg. Neurologic examination revealed no abnormalities. Normal hematologic studies included angiotensin-converting enzyme, VDRL test, HIV, West Nile virus and Lyme antibodies, erythrocyte sedimentation rate, extractable nuclear antigens, and double-stranded-DNA. Cerebrospinal fluid (CSF) analysis was unremarkable, including cell count, glucose, protein, herpes simplex virus PCR, cryptococcal antigen, gram stain, bacterial culture, fungal stain/culture, and acid-fast culture. While CT of the brain was normal, MRI reportedly showed abnormal punctate enhancing areas within the leptomeninges, involving frontal, parietal, and occipital lobes. The patient was treated symptomatically with promethazine, hydrocodone-ibuprofen, and alprazolam, and her atenolol dosage was increased prior to discharge.
Six days later, she was found to be confused with weakness in the left arm and was brought to our hospital. On examination, the patient was afebrile with blood pressure of 208/110 mm Hg. She was not oriented to place and time. Speech demonstrated mild dysarthria. There was neglect for visual and tactile stimuli on the left. She had a right-gaze preference overcome with oculocephalic maneuver. There was a left homonymous hemianopia on confrontation visual field testing. The patient demonstrated visual allochiria; when fingers were presented in her left visual field, she would report them in her right visual field. She had difficulty producing voluntary saccades to verbal command and voluntary saccades between targets and could not pursue beyond the midline to the left. When presented with a complex visual scene (the National Institutes of Health Stroke Scale “cookie theft” picture), she was able to identify individual items but could not describe the scene as a whole. Her visual acuity could not be accurately measured, but near vision was sufficient to identify elements of the cookie theft picture. There was a left lower facial droop. Strength was normal except for the left arm, judged to be 3/5 on the Medical Research Council scale. Arm reaching under visual guidance was abnormal; on the left, the abnormality was out of proportion to her degree of weakness.
Initial CT of the brain demonstrated a region of hypodensity in the right occipital lobe extending into the high right parietal lobe consistent with evolving acute infarction. Comprehensive laboratory evaluation was notable for elevated serum erythrocyte sedimentation rate and C-reactive protein and low serum sodium. Brain MRI performed 24 hours after the presentation was consistent with acute infarction in the distribution of the right middle and posterior cerebral arteries (Fig. 1). There was no evidence of cerebral venous thrombosis on CT venography. MRA of the head and neck showed 60% focal narrowing of the right internal carotid artery just proximal to the origin of the right posterior communicating artery. Nine days later, brain MRI showed areas of hyperintensity on diffusion-weighted imaging on both sides of the brain, consistent with the new regions of subacute infarction (Fig. 2). Repeat MRA revealed focal narrowing of multiple arteries in the region of the circle of Willis (Fig. 3). Conventional angiography exhibited beading of branches of the middle cerebral and anterior cerebral arteries bilaterally consistent with a vasculopathy and 75% stenosis of the paraclinoid segment of the distal right internal carotid artery.
Because of the possibility of CNS vasculitis, the patient was empirically treated with a short course of high-dose intravenous steroids. Minimal subjective improvement was noted. RCVS now was felt to be the most likely diagnosis prompting initiation of oral verapamil.
One month later, the patient was fully oriented, had improved left arm strength, and a left homonymous hemianopia. She was able to gaze to the left but still demonstrated mild ocular apraxia with difficulty initiating voluntary saccades. Visually guided reaching was much improved, and visual allochiria was no longer present. Brain MRI and MRA showed evolutionary changes of previously noted infarcts. The area of stenosis in the supraclinoid portion of the right internal carotid artery was unchanged, but there was a near complete resolution of the multifocal segmental arterial stenoses (Fig. 4).
Our patient presented with the classic symptom triad of Bálint syndrome, although the initial CT and MRI revealed infarction limited to the right hemisphere. Several days later, repeat MRI demonstrated infarction involving the left parietal and occipital lobes. One possible explanation for this disconnection in clinical and neuroimaging findings is the occurrence of a functional cerebral diaschisis. Diaschisis refers to depressed metabolic function of cortex in a region anatomically distant from, but functionally connected to, a region of injury (7). Several types of diaschisis have been described: remote effects within the injured hemisphere (ipsilateral effects), remote effects in the uninjured hemisphere (contralateral effects), and effects on the cerebellum contralateral to the cerebral injury (crossed cerebellar diaschisis) (8). Diaschisis has been examined in preclinical and clinical studies including various measures of cortical function, such as metabolic factors, cerebral blood flow, and electrical activity (8–12). In our patient, right parietal-occipital ischemia may have caused contralateral diaschisis mediated by callosal or extracallosal neuronal connections.
Alternatively, infarction of the right parietal-occipital region with concurrent left parietal-occipital ischemia without infarction (i.e., ischemic penumbra) may have led to Bálint syndrome in our case. Such a dissociation of clinical and neuroimaging findings has been described in a patient with reversible Bálint syndrome due to systemic hypotension and vertebral artery stenosis (13). Although not performed, functional perfusion imaging may have confirmed the presence of an ischemic penumbra in our patient.
Allochiria is a rarely reported phenomenon in which a stimulus presented to one side of the body is reported to be present on the other side (14). It was first described with tactile stimuli but may also occur with visual, auditory, or olfactory stimuli (14). The underlying neuroanatomic localization resulting in allochiria is variable; for example, allochiria may result from a primary sensory disturbance, such as tactile allochiria in the setting of myelopathy and dorsal column dysfunction or as an attentional deficit in the setting of neglect and right parietal lobe dysfunction (15). In some patients, allochiria may be misinterpreted as right-left confusion. Although right-left confusion has been observed in conjunction with Bálint syndrome (16), the phenomenon observed in our patient was limited to a transposition of visual stimuli from the left to right hemispace, rather than a more general disorientation of right versus left.
Alternative pathologies and lesion localizations may mimic the features of Bálint syndrome, and these features may be dissociable (4,17). Isolated ocular apraxia can occur with bilateral frontoparietal lesions (18,19). Optic ataxia has been associated with lesions of the parietal-occipital junction (20,21). Simultagnosia has been described with disorders of bilateral inferior parietal cortex, left extrastriate cortex, and bilateral superior visual association cortex (17,22). Severe restriction of visual fields can mimic simultagnosia as demonstrated by Dalrymple et al (5). The global impairment seen in patients with Bálint syndrome may be the result of a narrowed attentional window rather than an additional attentional deficit unique to the disorder (5). It is possible that simultagnosia or a limited visual attention (e.g., severely constricted visual fields) may cause difficulties with reaching in 3-dimensional space mimicking optic ataxia (5). However, such a deficit would not produce difficulty with voluntary saccades, impaired pursuit movements, or visual allochiria. In addition, optic ataxia and ocular apraxia are not typical features of severe visual field deficits. Patients with hemineglect may have impaired visual search (resembling ocular apraxia), impaired visually guided hand movements (resembling optic ataxia), and visuoperceptual difficulties (mimicking simultagnosia) (4). Hemineglect could contribute or compound the difficulties with search and attention seen in patients with Bálint Syndrome.
Our patient initially presented with a thunderclap headache triggered by Valsalva maneuver and subsequently experienced ischemic strokes in multiple vascular territories. Neuroimaging demonstrated multifocal arterial stenoses consistent with the vasculopathy RCVS. Patients with RCVS typically present with thunderclap headache, often triggered by exertion or Valsalva maneuver, and can have any number of neurologic deficits (6,23). Following treatment with a calcium channel blocker, diminished cerebral vasospasm within 4 weeks is common (6). In our patient's case, a negative vasculitis workup, normal CSF, and rapid clinical-neuroimaging improvement with verapamil are additional features supportive of the diagnosis of RCVS.
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