81616ournal of Neurology, Neurosurgery, and Psychiatry 1993;56:816-819 SHORT REPORT Hemineglect and seizures in Binswanger's disease: clinical-pathological report Stephan A Mayer, Thomas K Tatemichi, Laura S Hair, James E Goldman, Ann Camac, J P Mohr Abstract The range of clinical effects from ischaemic damage to white matter in Binswanger's disease has not been fully characterised. Although focal deficits and seizures occur frequently, superficial infarcts often coexist, making the cause of these symptoms unclear. The case of a 69 year old woman is described who presented with acute left sided weakness and hemispatial neglect, followed a year later by electrographically documented seizures originating from the right hemisphere. Interim examinations showed bilateral pyramidal signs and mild intellectual decline. Serial CT and MRI studies showed bilateral diffuse ischaemic lesions of the cerebral white matter and old left sided lacunar infarcts but no evidence of acute infarction. Post- mortem examination showed gliosis and demyelination of the deep white matter which spared the subcortical arcuate fibres; this is consistent with Binswanger's disease. The neocortex was normal. This case and previous reports indicate that focal symptoms typically referable to the grey matter, including hemineglect and seizures, may occur as a manifestation of subcortical ischaemic injury to white matter in Binswanger's disease. Departnent of Neurology S A Mayer T K Tatemichi A Camac J P Mohr Department of Pathology L S Hair J E Goldman Columbia University, College of Physicians and Surgeons, New York, New York, United States Correspondence to: Dr T K Tatemichi, Stroke and Aging Research Project, Neurological Institute, 710 West 168th Street, New York, NY 10032, USA. Received 15 May 1992 and in revised form 31 July 1992. Accepted 11 August 1992 whose postmortem examination showed only subcortical lesions in white matter consistent with Binswanger's disease. Case report A 69 year old right handed woman was first admitted to the Neurological Institute with acute left sided weakness and hemispatial neglect. She had a long history of treated hypertension but no history of stroke, dementia, or seizures. On admission her blood pressure was 230/120 mm Hg. She was alert but disoriented to place and time, with dysarthric, perseverative speech and rightward head turning. She bisected a line to the right and failed to draw numerals on the left side of a clock face. There was no visual field cut, aphasia, anosognosia, or asomatagnosia. Cranial nerves were normal except for a gaze preference to the right and flattening of the left nasolabial fold. She had a moderate left hemiparesis, 4/5 in the arm and leg, with deficits to light touch, pinprick, graphesthesia, and double simultaneous stimulation on the left side. Deep tendon reflexes were active but symmetrical and the toes withdrew bilaterally. Coordination testing was performed slowly on the left, without dysmetria or ataxia. Gait could not be tested. CT on admission showed generalised cerebral atrophy, prominent bilateral patchy (9 Neurol Neurosurg Psychiatry 1993;56:816-819) lucencies in the centrum semiovale and corona radiata (figure 1), and discrete lucencies of Binswanger's disease is a progressive form of the left posterior internal capsule and upper vascular dementia resulting from diffuse and pons consistent with old lacunar infarction. multifocal ischaemic damage to subcortical CTs obtained 2 and 14 days later showed the white matter. Although the pathological fea- same results. An EEG on admission and two tures of the disease have been well defined,'-3 weeks later showed continuous polymorphic their relation to focal symptoms or signs in delta activity over the right hemisphere. the course of the disease remains uncertain. Doppler ultrasound studies showed normal In a recent review by Babikian and Ropper flow velocities in the internal carotid and focal neurological deficits occurred in 55% vertebral arteries. Electrocardio-graphy, echoand seizures in 18% of 47 pathologically veri- cardiography, Holter monitoring, and procofied cases of Binswanger's disease.3 The fre- agulant studies gave normal results; quent coexistence of cortical and lacunar erythrocyte sedimentation rate was normal infarcts3 and the retrospective nature of the and tests for venereal disease gave negative diagnosis (with imperfect historical informa- results. She was treated with aspirin and nifedipine. tion) have limited previous attempts to correlate focal neurological signs and pathological By the time of discharge 20 days later her changes in patients with the disease. We strength had fully recovered, but mild signs of describe the case of a patient with acute non- left sided hemineglect and sensory loss dominant hemispheric deficits and seizures persisted. Hemineglect and seizures in Binswanger's disease: clinical-pathological report Figure 1 CT on presentation (top) showed moderate atrophy and diffuse patchy areas of low density in the centrum semiovale and corona radiata. T2 weighted magnetic resonance images obtained two months after patient's initial admission (bottom) showed multiple foci of increased signal in a similar distribution. Allfollow up studies gave same results. 817 Three months after discharge, members of her family noted new difficulty with memory, affective lability, and paranoid ideation. On examination she was disoriented to year, with hypophonic, perseverative speech and impaired short term recall. She displayed constructional apraxia on clock drawing but showed no signs of neglect, sensory loss, or weakness. Rapid alternating movements were slow bilaterally, reflexes were symmetrical, and Babinski's sign was absent. She walked with a decreased armswing on the left and was unable to walk in tandem. T2 weighted magnetic resonance imaging obtained two and eight months after the initial stroke showed generalised atrophy with multiple foci of increased signal in the bilateral fronto parietal white matter, left brachium pontis, and left upper pons (fig 1). One year after her first admission, she presented with seizures characterised by leftward head and eye deviation, left beating nystagmus, and tonic contractions of the left arm and leg with occasional clonic movements. Her blood pressure was 200/100 mm Hg. After treatment with intravenous phenytoin she was oriented only to name, with diminished verbal output, left hemineglect, and moderate left hemiparesis. By the following day her left motor signs had improved, with only slowed rapid alternating movements evident, but signs of hemineglect persisted. A CT of the head showed the same as the previous studies. On her second day in hospital further seizure activity was noted with eye blinking, inattention, and left arm posturing. Electroencephalopathy showed an electrographic seizure originating from the right fronto temporal region, unreactive continuous polymorphic delta and periodic lateralising epileptiform discharges over the right hemisphere, and diffuse slowing without a posterior dominant rhythm. Her seizures were subsequently controlled with the addition of phenobarbitone. On the fifth day in hospital she died of cardiac arrest. PATHOLOGICAL FINDINGS Macroscopic description The fresh brain weighed 1130 g. There was generalised moderate sulcal and gyral atrophy with no external signs of discoloration or softening. The blood vessels at the base of the brain showed mild evidence of atherosclerosis. Although the cortical grey matter appeared grossly normal, the subjacent white matter was gliotic throughout both hemispheres. These changes were patchy, symmetrical, and most severe in the posterior parietal lobes (fig 2). A cystic area measuring 0-4 cm in diameter was noted in the right centrum semiovale, with a similar lesion on the left. Sequential sections of the brainstem and cerebellum were macroscopically normal. Figure 2 Coronal sections at level of anterior thalamus (top) and occipital horns (bottom) showing severe gliotic changes bilaterally in subcortical white matter (left side is to reader's left). Microscopic description Arterioles throughout the subcortical white matter displayed markedly thickened and fibrotic walls (fig 3). Atherosclerotic plaques 818 Mayer, Tatemichi, Hair, Goldman, Camac, Mohr Figure 3 Marked arteriolar thickening and severe myelin loss in deep hemispheric white matter (Luxolfast blue-periodic acid-Schiff stain, magnification x 200). basal ganglia, or frontal-parietal white matter is a well described cause of neglect synO.y dromes,45 the unusual feature of our case is the occurrence of hemineglect in the presence of incomplete white matter infarction.6 Focal neurological deficits consistent with stroke or transient ischaemic attack occur in 60% of patients with Binswanger's disease at some point during the illness.23 Among 47 cases of the disease with complete pathologiE *->o cal reports reviewed by Babikian and Ropper, - fi lacunar infarcts were found in 93% and cortical infarcts in 33% of cases.' Accordingly, lacunar syndromes (especially pure motor stroke) are the most common acute focal deficits in Binswanger's disease.2 However, Figure 4 Subcortical several instances of persistent focal cortical demyelination with sparing deficits (incorporating aphasia,7 hemianopia,89 of arcuate Ufibres (Luxol fast blue-periodic and apraxia'0) have been described in patients acid-Schiff stain, in whom the corresponding neocortex was magnification x 40). normal on neuropathological examination. These cases and our case support the view proposed by Lassen that incomplete ischaemic damage to the deep white matter can result in persistent focal deficits indistinguishable from those typically associated with acute infarction.11 Positron emission tomography studies showing both diffuse'21' and focal'2 reductions in cerebral blood flow in cortical regions overlying large confluent white matter lesions on MRI or CT suggest were noted in the pial arteries ancI to a lesser that such deficits may occur on the basis of extent in the medullary cortical ve ssels. There cortical deafferentation. was extensive demyelination Xand gliosis Seizures are widely recognised as part of throughout the white matter, mo st severe in the clinical spectrum of Binswanger's disease2 3 the posterior parietal and occipital lobes. The but have received limited attention, perhaps demyelination spared the arcuate fibres and because of uncertainty about their origin. We was most severe in the deep and pieriventricuhave identified 10 previously reported cases lar regions (fig 4). Bielschowsky's silver stain of Binswanger's disease associated with showed a decrease in axonal fibre s, although seizures.'9 '4-9 One patient experienced parthey were spared compared with the loss of tial motor seizures after a hemiparesis, and in myelin. Several microscopic area s of infarc- this case a cortical infarct was identified that tion were noted in the left basal Iganglia and may have been responsible.' In two cases bilateral thalamus and pons; thes;e were not metabolic derangements may have precipitatapparent macroscopically. ed the seizures.9 Otherwise, unprovoked Nine sections of bilateral front:al, parietal, recurrent generalised tonic-clonic seizures are and occipital neocortex were examined, the rule, typically appearing late in the course including the posterior parietal lobes overly- of the illness. In some instances seizures ing the most severely affected wi hite matter. marked the onset of either a transient'4 '5 or In these regions the neuronal 1populations permanent'6 17 focal neurological deficit. The were normal with no evidence o: f ischaemic corresponding cortical areas in these patients tissue damage. A moderate numbe-r of diffuse were described as macroscopically normal, as amyloid plaques and neurofibrilllary tangles was the case in our patient. were scattered throughout the basa al forebrain The EEG finding of periodic sharp wave and the frontal and occipital co: rtices; they complexes in Binswanger's disease has been were no more than would be exypected with previously noted in a patient who had no normal ageing. seizure activity.20 However, electrographic seizures arising from pathologically normal areas of cortex have not been previously docDiscussion umented in the disease. Four days before her Our patient presented first witd h a stroke death our patient presented with recurrent characterised by non-dominant Eiemispheric left sided weakness and neglect in the setting deficits and later with seizures, wiith evidence of simple partial and complex partial status of intellectual deterioration in td he interim. epilepticus. We cannot determine whether Postmortem findings showed p wathological these symptoms were triggered by a new changes of the type typicallyr seen in subcortical ischaemic event or represented Binswanger's disease, with no evidence of seizures with Todd's paralysis. Nevertheless, large deep cavitary lesions or injjury to the the EEG and pathological findings indicate neocortex. Although large subcori tical infarcthat the subcortical ischaemic demyelinating tion affecting the non-dominant thalamus, lesions were probably responsible. Although . W ,0.0 . . t- F ':: Hemineglect and seizures in Binswanger's disease: clinical-pathological report seizures are typically thought to result from disease of the cortex, a well defined risk of epilepsy has been identified in other diseases of the white matter as well-for example, multiple sclerosis2' and progressive multifocal leucoencephalopathy.2 The full range of focal symptomatology associated with white matter ischaemia in Binswanger's disease is poorly understood. Vague terms such as stroke-like events3 and transient neurological phenomena2 abound in published reports, illustrating the sometimes atypical fluctuating symptoms seen in the disease. Babikian and Ropper have argued that Binswanger's disease should be recognised as an entity distinct from multi-infarct dementia because of both the characteristic pathology and the "irregularity and inconsistency of [the] focal stroke syndromes". 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