CLINICAL NUCLEAR MEDICINE Volume 18, Number 5, pp 409-412 © 1993, J. B. Lippincott Co. Hyperemic Receptive Aphasia on NeuroSPECT DAVID H. LEWIS, M.D.,* W. T. LONGSTRETH, Jr., M.D.,t ROBERT WILKUS, M.D.,t NeuroSPECT of regional cerebral blood flow (rCBF) with Tc-99m HMPAO demonstrated left temporoparietal hy- peremia in two patients with acute receptive aphasia. This finding prompted further testing with electroen- cephalography that added to the impression of ictal dys- phasia. The differential diagnosis in one case Included complicated migraine. NeuroSPECT depicts blood flow abnormalities in acute aphasic disorders, either due to ischemia, which is most commonly the cause, or due to hyperemia secondary to migraine or epilepsy. The treat- ment and prognosis of these latter conditions differ from stroke, and thus SPECT plays a role in patient manage- ment. Te ONSET OF FLUENT or receptive aphasia, known by the eponym Wernicke’s aphasia, often is associ- ated with ischemia or infarction in the parietotemporal region of the dominant hemisphere of the brain. Other possibilities in the differential diagnosis of this syn- drome include tumor or trauma, and, less commonly, epilepsy and migraine (1). Differentiation of dysphasia from a psychiatric process sometimes can be difficult. The standard evaluation of a patient with this syn- drome includes a thorough neurologic examination and often a head CT, which in the setting of early ischemia or infarction may be negative. This report presents two patients with receptive aphasia in whom neuroSPECT added useful clinical information to the standard evaluation. Case Reports Case | A 19-year-old, right-handed woman with the syn- drome of mitochondrial myopathy, encephalopathy, — Received for publication May 8, 1992; accepted June 29, 1992, Reprint requests: David H. Lewis, M.D, Director, Nuclear Med- icine, Harborview Medical Center, ZA-44, 325 Ninth Avenue, Se- attle, Washington 98104, AND MICHAEL COPASS, M.D.+ From the Department of Radiology, Division of Nuclear Medicine,* and the Department of Medicine, Division of Neurology,} Harborview Medical Center, University of Washington, Seattle, Washington a lactic acidosis, and stroke-like episodes (MELAS) (2) presented with hearing loss and a fluent dysphasia. Her problem began with a severe headache that oc- curred intermittently since a young age and had been diagnosed as migraine. In the past she had two epi- sodes suggesting stroke: one involving the left occipi- tal lobe and the other the right parieto-occipital region. She also had partial complex seizures. Although a muscle biopsy had failed to reveal ‘‘ragged-red”” fi- bers, she had elevated lactic acid levels in her serum, and a point mutation in her mitochondrial DNA, as described in other patients with MELAS (3). Neuro- logic examination showed an alert and awake woman, full motor strength, no somatosensory deficits, normal deep tendon reflexes, and negative plantar reflexes. She had decreased verbal comprehension, word-find- ing difficulties, word substitution, and word salad. Computed tomography showed a right posterior tem- poroparietal hypodensity and a more recent left supe- rior temporal hypodensity (Fig. 1A). Because of the new onset of apparent deafness, the patient underwent audiometry that showed normal stapedius reflexes bi- laterally, but there was no behavioral response to sound, . On the same day as the CT, neuroSPECT was ob- tained | hour after intravenous administration of 30 mCi Tc-99m HMPAO (Ceretec; Amersham-Medi- Physics, Arlington Heights, IL) with a GE 400 AT gamma camera (GE Medical Systems, Milwaukee, WI) linked to a Siemens Microdelta Computer (Sie- mens, Hoffman Estates, IL). Images demonstrated hy- peremic flow in the left posterior temporoparietal re- gion, with increased uptake in the right cerebellar 409 410 CLINICAL NUCLEAR MEDICINE May 1993 Vol. 18 Fig. 1. (A) Head CT scan with contrast on initial presentation of patient in case 1. Note right parieto-occipital hypodensity and incidental appearance of basal ganglia calcification. (B) Head CT scan without contrast at 10 months after presentation. Note interval development of left frontal hypodensity. No abnormality is present in the left temporoparietal region. hemisphere, a small focal deficit in the posterior left frontal region, and a large zone of severely reduced flow in the right parieto-occipital region (Fig. 2). The zone of hyperemia (increased uptake) was distinctly abnormal, because the rest of the brain unaffected by the deficits mentioned had more uniform uptake. Twenty-four hour telemetry electroencephalo- graphic monitoring beginning after the SPECT showed no frank seizures, but there was frequent epileptiform activity over the left hemisphere, especially over the inferior frontal, anterior temporal, and midtemporal regions. The patient’s receptive aphasia gradually resolved over the next several days and the patient was dis- charged. She was readmitted several days later with partial seizures that were characterized by right sco- tomata, and right hand and face motor activity. Anti- convulsant medication was adjusted and the patient was discharged. A follow-up CT done 10 months later showed hypodensity in the left frontal lobe and the right temporal, right parietal, and right occipital cortex (Fig. 1B). The sole new finding was in the left frontal lobe. No abnormality was seen in the left temporopa- rietal region. Case 2 A 62-year-old, right-handed woman who carried the diagnosis of bipolar affective disorder with occasional psychotic episodes was admitted to the hospital after an early morning event in which the husband de- scribed the patient as becoming ‘‘blue with arms stiff and reaching out and then speaking in an unknown language.”’ On neurologic examination the patient was alert but talking nonsense, nonstop and incomprehen- sibly. She was unable to follow any commands; motor Fig. 2, NeuroSPECT on the same day as the CT in Figure 1A. Displayed are two- pixel-thick slices #1 (at cerebellar level) and #6. Note hyperemia in the left temporopari- etal cortex and asymmetrically increased up- take in the right cerebellar hemisphere (ar- rows). A large zone of markedly decreased uptake is noted in the right parieto-occipitat region. No. 5 RECEPTIVE APHASIA SPECT « ps cerebellar hemisphere (arrows). strength was full; sensory examination was intact; deep tendon refiexes were symmetric, and plantar re- flexes were normal. Initial and repeat head CT scans done 4 days apart were negative. On the day after the first CT scan, the patient was injected with 30 mCi of Tc-99m HMPAO while she continued to speak incomprehensibly. NeuroSPECT was obtained | hour later. Images revealed increased regional cerebral blood flow in the left posterior tem- poroparietal area (Fig. 3). Because the patient was too uncooperative to lay still for the SPECT acquisition, a benzodiazepine was administered after the radiophar- maceutical injection, and the patient came to the nu- clear medicine department asleep. After she awoke hours later, she was no longer aphasic. Electroencephalography done the next day showed some bitemporal epileptiform discharges. A cerebral angiogram lacked evidence for vasculitis or other find- ings to explain her course. The patient was treated with carbamazepine for pre- sumed temporal lobe epilepsy. Discussion Receptive aphasia is a neurologic syndrome usually associated with an ischemic event that neuroSPECT should detect before a CT abnormality is present (4,5). In the cases presented, the unexpected appearance of hyperemia in Wernicke’s area shown by SPECT had implications for the patients’ further diagnostic testing and treatment. This finding also was associated with a more favorable prognosis than may have been ex- pected with ischemic stroke. In the first case, the SPECT interpretation was more challenging than in the second due to the number of Lewis, Longstreth, Wilkus, and Copass Ait Fig. 3. NeuroSPECT in case 2, Slices #1, 4, and 7 are displayed, showing left temporoparietal hyperemia and increased uptake in the right abnormalities. The differential diagnosis of the finding of hyperemia is between seizure activity (most likely, in the opinion of the authors) (6) causing the aphasic syndrome, and the vasodilatory phase of migraine, which is less likely because the oligemic phase of complicated migraines usually is that associated with neurologic signs and symptoms (7-10). Hyperemia in migraine has been previously reported with the use of Xe-133 SPECT (8). Luxury perfusion is not likely be- Cause the patient never had a left temporoparietal in- farct. With embolic events, however, it is possible that early reperfusion into an area that has lost its circula- tory autoregulation may result in hyperemia without infarction. The finding of the increased right cerebellar hemisphere perfusion is somewhat problematic. In- deed, with the presence of the old right parieto-occip- ital infarct in this patient, it could have represented crossed cerebellar diaschisis of the left cerebellar hemisphere. Yet, because of the presumed increased neuronal activity due to the ictus in the left temporopa- rietal region, the right cerebellar hemisphere may have been responding to the increased contralateral activity by increasing its own activity, and, therefore, also its own blood flow. The second case almost certainly is ictal dysphasia. Because this patient did not have an infarct or head- ache, migraine should not enter into the differential diagnosis. As mentioned earlier, the hyperemia in this case could have been due to early reperfusion of an embolic occlusion before cerebral damage had oc- curred, but during a period of blood flow disregulation. The prolonged time course of this patient’s symptoms, however, would have implied a much longer period of ischemia that might have resulted in a detectable CT 412 abnormality and would have appeared as a SPECT rCBF deficit. ; SPECT imaging of regional cerebral blood flow has been reported in MELAS syndrome with use of both of the radiopharmaceuticals approved by the FDA: 1-123 IMP and Tc-99m HMPAO (11,12). Morita et al described increased uptake of IMP, whereas Grun- wald et al described areas of reduced uptake of HMPAO resembling Alzheimer’s-type dementia. Case #1 had the elements of reduced uptake in the right temporoparieto-occipital region, similar to the latter report, but also showed the zone of increased uptake, or hyperemia, in the contralateral brain, which was interpreted as most likely representing seizure activ- ity, and, less likely, migraine. Morita et al postulated that the increased uptake was due to epileptic foci or hyperemia due to local lactic acidosis (11). Decreased uptake may be due to reduced cerebral function or blood flow impairment caused by mitochondrial angi- opathy in cerebral vessels (12,13). Migraine and epilepsy are paroxysmal disorders that, at times, may be difficult to distinguish, particu- larly in the younger population (14). Prevalence rates for migraine vary from 1% to 25%, and disturbances in speech are more common in complicated migraine than usually is estimated. Receptive aphasia has been reported (1). Nonconvulsive seizures occur in over 60% of people with epilepsy in the United States (15). Special sensory attacks usually represent auras to complex partial or generalized seizures in epilepsy and may be detected by cerebral blood flow imaging with Tc-99m HMPAO SPECT (16). In and of themselves, simple partial special sensory seizures that do not propagate or become generalized have an incidence of 0.2/1000 in the general epilepsy population (1). Simple, continuous (status epilepticus), and paroxysmal ictal dysphasias have been described as well (17-20). Knight and Cooper raised the important issue of in- cluding epilepsy in the differential diagnosis of Wer- nicke’s aphasia and the caveat of misdiagnosing so- called ‘‘psychotic breaks’’ as responsible for the “‘word salad”’ of certain patients who might have ep- ilepsy (20). In conclusion, the main points of this article have been to demonstrate to health care practitioners that not all acute aphasias have an ischemic etiology, and that neuroSPECT contributes to the differential diag- nosis and planning for further testing; and to underline the challenging aspects of neuroSPECT interpretation for nuclear medicine practitioners, because the brain manifests wide variations in pathologic blood flow that must be understood in relation to the disease at hand (especially in unusual disorders such as MELAS). CLINICAL NUCLEAR MEDICINE May 1993 Vol. 18 Thus, it is essential to correlate SPECT results with other neuroimaging techniques and neurodiagnostic tests, to know the strengths and weaknesses of each, and to recognize the complementary nature of func- tional and structural brain imaging. References 1. Ziegler DK, Friedman AP (Migraine); Goldensohn ES, Glaser GH, Goldberg MA (Epilepsy): Intermittent or paroxysmal disorders. In Roland LP (ed): Merritt’s Textbook of Neurol- ogy, 8th ed. Philadelphia, Lea and Febiger, 1989, pp 773-804. 2. Pavlakis SG, Phillips PC, DiMauro S, et al: Mitochondrial my- opathy, encephalopathy, lactic acidosis, and stroke-like epi- sodes: a distinctive clinical syndrome. Ann Neurol 16:481, 1984, 3. Hammans SR, Sweeney MG, Brockington M, et al: Mitochon- drial encephalopathies: molecular genetic diagnosis from blood samples. Lancet 337:1311, 1991, 4. O'Leary DH, Hill TC, Lee RG, et al: The use of 123-iodoam- phetamines and single photon emission computed tomogra- phy to assess local cerebral blood flow. AJNR 4:547, 1983. 5. Neirinckx R, Canning L, Piper I, et al: Technetium-99m d, 1-HM-PAO: a new radiopharmaceutical for SPECT imaging of regional cerebral blood flow. J Nucl Med 28:191, 1987. 6. Lee BI, Markand ON, Wellman HN, et al: HIPDM-SPECT in patients with medically intractable complex partial seizures: ictal study. Arch Neurol 45:397, 1988. 7. Lauritzen M, Skyhoj-Olsen T, Lassen NA, Paulson OB: Changes in regional blood flow during the course of classic migraine attacks. Ann Neurol 13:633, 1983. 8. Olesen J, Larsen B, Lauritzen M: Focal hyperemia followed by spreading oligemia and impaired activation of rCBF in classic migraine. Ann Neurol 9:344, 1981. 9. Leao APP: Spreading depression of activity in cerebral cortex. J Neurophysiol 7:359, 1944. 10. Podreka I, Suess E, Goldenberg G, et al: Initial experience with with technetium-99m-HM-PAO brain SPECT. J Nucl Med 28:1657, 1987. 11. Morita K, Ono S, Fukunaga M, et al: Increased accumulation of N-isopropyl-p-(I-123)-iodo-amphetamine in two cases with mitochondrial encephalomyopathy with lactic acidosis and stroke like episodes. Neuroradiology 31:358, 1989. 12. Grunwald F, Zierz 8, Broich K, et al: HMPAO-SPECT imaging resembling Alzheimer-type dementia in mitochondrial en- cephalomyopathy with lactic acidosis and stroke-like epi- sodes (MELAS). J Nucl Med 30:1740, 1990. 13. Ohama E, Ohara S, Ikuta F, et al: Mitochondrial angiopathy in cerebral blood vessels of mitochondrial encephalomyopathy. Acta Neuropathol 74:226, 1987. 14, Pedley TA: Differential diagnosis of episodic symptoms. Epi- tepsia 24(Suppl 1):S31, 1983. 15. Goldensohn ES: The non-convulsive epilepsies: clinical mani- festations, diagnostic considerations and treatment. Epilepsia 24(Suppl 1):S5, 1983. 16. Ramsay SC, McLaughlin AF, Greenough R, et al: Comparison of independent aura, ictal and interictal cerebral perfusion. J Nucl Med 33:328, 1992. 17. De Pasquet EG, Gaudin ES, Bianchi A, De Mendilaharsu SA: Prolonged and monosymptomatic dysphasic status epilepti- cus, Neurology 26:244, 1976. 18. Hamilton NG, Matthews T: Aphasia: the sole manifestation of focal status epilepticus. Neurology 29:745, 1979. 19. Rosenbaum DH, Siegel M, Barr MA, Rowan AJ: Epileptic aphasia. Neurology 36:822, 1986. 20. Knight RT, Cooper J: Status epilepticus manifesting as revers- ible Wernicke’s aphasia. Epilepsia 27:301, 1986.