Medicine, Miami, provided expertise in determin¬ ing the metabolic studies in case 1. References 1. Venkata C, Fishcer A, McClean W: Cerebellar hemorrhage complicating isovaleric acidemia. Neurology 1981;31:746-748. 2. Volpe J: Neurology of Newborn Vol. XXII in Major Problems in Clinical Pediatrics. Philadelphia, WB Saunders Co, 1981, pp 383-403. 3. Inoue S, Krieger I, Sarnaik A: Inhibition of bone marrow stem cell growth in vitro by methylmalonic acid. Pediatr Res 1981;15:95-98. 4. Shuman RM, Leach RW, Scott CR: The neuropathology of non-ketotic and ketotic hyperglycinemias: Three cases. Neurology 1978;28:139\x=req-\ 146. 5. Baumgartner K, Ando T, Nyhan WL: Non\x=req-\ ketotic hyperglycinemia. J Pediatr 1969;75:1022. 6. Slager UT, Berggrem RC: Non-ketotic hyperglycinemia: Report of a case and review of clinical, chemical and pathological changes. Ann Neurol 1977;1:399. 7. Ziter FA, Bray PF, Madsen JA: The clinical findings in a patient with non-ketotic hyperglycinemia. Pediatr Res 1968;2:250. 8. Anderson JM: Spongy degeneration in the white matter of the CNS in the newborn: Pathological findings in those infants, one with hyperglycinemia. J Neurol Neurosurg Psychiatry 1969; 32:328. 9. Friede RL: Developmental Neuropathology: Dysplasias of Cerebellar Cortex. New York, Springer Publishing Co Inc, 1975, pp 336-338. 10. Pape KE, Armstrong DL, Fitzhardinge PM: CNS pathology associated with mask ventilation in the very low birth weight infant: A new etiology for intracerebellar hemorrhage. Pediatrics 1976;58:473. 11. Pearson HA, Shulman NR, Marder VJ, et al: Isoimmune neonatal thrombocytopenia purpura. Blood 1964;23:154. 12. Simmons MA, Adcock EW, Bard H, et al: Hypernatremia and intracranial hemorrhage in neonates. N Engl J Med 1974;291:6-11. 13. Corbet AJ, Adams JM, Kenny JD, et al: Controlled trial of bicarbonate therapy in high$risk premature newborn infants. J Pediatr 1977; 91:771-776. 14. Luttrel C, Finberg L, Drawdy LP: Hemorrhagic encephalopathy induced by hypernatremia: II. Experimental observations on hyperosmolality in cats. Arch Neurol 1959;1:153-160. 15. Finberg L: Dangers to infants caused by changes in osmolal concentration. Pediatrics 1977;91:777-778. 16. Finberg L: The relationship of intravenous infusions and intracranial hemorrhage: A commentary. J Pediatr 1977;91:777-778. 17. Papile L, Burstein J, Burstein R, et al: Relationship of intravenous sodium bicarbonate infusions and cerebral intraventricular hemorrhage in prematures. J Pediatr 1978;93:834-838. 18. Cavazzuti M, Duffy TE: Regulation of local CBF in normal and hypoxic newborn dog. Ann Neurol 1982;11:247-257. 19. Powell CL, Hernandez MJ, Vannucci RC, et al: The effect of lactacidemia on regional cerebral blood flow in newborn dog. Ann Neurol 1981; 10:295. Aphasia After Left Thalamic Infarction Philip B. Gorelick, MD; Daniel B. Hier, MD; Louis Benevento, PhD; Susan Levitt, MS; Walter Tan, MD \s=b\ We examined a 70-year-old woman who became aphasic after a left thalamic infarction. Computed tomographic scan showed injury that was largely limited to the ventral anterior and rostral ventral lateral thalamic nuclei. Speech was characterized by reduced voice volume, impaired auditory and reading comprehension, perseverations, intermittent use of jargon, fluctuations in the ability to perform confrontation naming, extraneous intrusions, verbal paraphasia, intact repetition skills, and fluent speech that was laconic but grammatically correct. We propose that the deficits after left thalamic injury can be grouped into the following four large clusters: extrapyramidal deficits (decreased or fading voice volume), deficits in lexical access (anomia, verbal paraphasia), deficits in vigilance (neologisms, intrusions, fluctuating performance, jargon, perseverations), and comprehension defects. (Arch Neurol 1984;41:1296-1298) Accepted for publication Dec 15, 1983. From the Departments of Neurology (Dr Gorelick), Anatomy (Dr Benevento), Otolaryngology, Speech, and Hearing (Ms Levitt), and Diagnostic Radiology (Dr Tan), The University of Illinois College of Medicine, Chicago, and the Department of Neurology (Stroke Service), Michael Reese Hospital and Medical Center, University of Chicago Pritzker School of Medicine (Dr Hier). Reprint requests to Cerebrovascular Service, Department of Neurology, University of Illinois College of Medicine, Chicago, IL 60612 (Dr Gorelick). following dominant hemiAphasia ^ sphere thalamic injury has been reported with infarction,14 hemor¬ sur¬ rhage,1·514 tumor,1518 stereotaxic 24 gery,1921 electrostimulation,22 arte¬ riovenous malformation,25 and ab¬ scess.26 Descriptions of aphasie syn¬ dromes are varied. Doubters have argued that the resulting disturbance is an elemental speech disorder rather than true language dysfunction.18 Pathologic and computed tomograph¬ ic studies indicate that some lesions may extend beyond the thalamic bor¬ ders to other subcortical and cortical language structures. We describe an infarction limited largely to the later¬ al-ventral thalamus associated with features of transcortical aphasia. REPORT OF A CASE A 70-year-old, right-handed woman was found wandering aimlessly on a street corner by the police in the early hours of the morning. She was last observed in her podiatrist's waiting room at 4 pm the day before. The police were notified when a relative who was to chauffeur her from the doctor's office reported her missing. Two days before the incident she had "snapped" angrily at her son, an uncharacteristic act for this individual. The night before her speech "did not sound exactly right." How¬ ever, the following morning, she spoke normally. The police officer who found her described her speech as incoherent. For the past several years, she had been a widow who lived independently in a retirement home for senior citizens. She rode the bus by herself to visit relatives and performed her own cooking, washing, and cleaning. Although she possessed only a grammar school education, she read dai¬ ly newspapers and magazines. Recently her vision had been failing due to cata¬ racts. She had insulin-dependent diabetes as well as hypertension treated with hydrochlorothiazide and methyldopa. She did not smoke cigarettes or drink alcohol and had no history of headaches. On physical examination her BP was 180/100 mm Hg and the radial pulse rate was 80 beats per minute. There were no bruits of the head or neck and facial pulses were symmetrical. The results of the gen¬ eral physical examination were unremark¬ able. The initial examination showed a pauci¬ ty of spontaneous speech. When prodded, she produced fluent empty speech contam¬ inated by neologisms, verbal and literal paraphasias. Voice volume was reduced. She could repeat "boy," "dog," "no if s and's, or but's about it," and "he and she and I are here." She was able to follow commands such as "point to the ceiling," "close your eyes," and "bend your neck." When instructed to place three differentsized pieces of tissue paper on three sepa¬ rate articles of furniture, she picked up each individual tissue paper and touched it to her nose. She correctly named a watch, a pen, and a spoon but called a cup "anoth¬ er." When a fork was displayed, the patient picked it up, studied it, and then placed it down on her lunch plate. When asked "What is your daughter's name?" she replied, "Every name to your daughter." She referred to her telephone number as "Willis" and stated "Who is in your fami¬ ly?" when asked to name her family mem¬ bers. She could read only two words from a Downloaded From: http://archneur.jamanetwork.com/ by a University of Missouri - St Louis User on 10/02/2013 Speech Profile (Boston Diagnostic Aphasia Examination)* Characteristic Melodic line Phrase length Articulatory agility +1 Grammatical form -I-1 Paraphasia in running speech Word finding Auditory comprehension (mean) Naming (mean) Repetition (mean) * Score +1 +1 —1.5 —1.5 —1.7 —1.0 0.0 Negative scores indicate greater impairment. correctly after visual clues were given. The following were preserved: comprehension of three-step commands; naming (ball, key, spoon, rubber band, wristwatch, buckle and sewing needle); repetition ("he and she and I" and "no if s and's or but's about it"); reading (newspaper); right-left orienta¬ tion; oral-buccal-lingual and limb praxis; finger identification; eye-hand coordina¬ tion; simultaneous visual perception; and revisualization ability. There was a subjec¬ tive increase to pinprick sensation on the left side of the face and trunk and the left arm, leg, and ear; a tremor of the out¬ stretched left upper extremity; slight pto¬ sis of the right eyelid; and a tendency to veer and stumble to the right on gait testing. Computed tomographic scan on third hospital day demonstrates nonenhancing lucency of left lateral-ventral thalamus. 17th hospital day, bilateral carotid and left vertebral angiography was performed. The findings included the following: a shallow plaque with ulcération at the junction of the left internal and common carotid arteries; a nonulcerating, shallow plaque in the distal right common carotid artery and proximal right internal carotid artery; and an area of focal narrowing in the right angular branch of the middle cerebral A CT scan of the thalamus at 1.5-mm intervals was obtained. Estimated ana¬ tomic reconstructions disclosed that the infarction involved the lateral nuclear group, ventral anterior nucleus (VA), ven¬ tral lateral nucleus (VL), anterior portion of the posterior limb of the internal capsule, and reticular nucleus bordering VA and VL. There was slight extension into the globus pallidus. COMMENT artery. simple paragraph at a third-grade level. When shown the word herd on an index card, she responded "rd." She was unable to write a sentence to dictation or to copy a model sentence. When asked to salute or show how a hammer is used, she did not respond. She imitated the examiner salut¬ ing when asked to do so. A demonstration by the examiner of hammering (without a hammer in hand) was followed by repeti¬ tive saluting with the right hand. Attempts at figure copying produced illeg¬ ible marks that did not resemble the mod¬ el. She was unable to describe the inside of a watermelon, the color of a fire engine, or the color of the grass. When asked to group similar pictured faces of unfamiliar indi¬ viduals, she correctly matched two pairs but attempted no more. Cranial nerves II through XII, visual fields, and results of funduscopic examina¬ tions were normal. An iridectomy scar was noted on the right side and a cataract in the left lens. Pinprick and other noxious stimuli were localized. With eyes closed, the patient correctly named a ball, a fork, and a comb when placed in either hand. Both upper extremities could be raised spontaneously above the head. She reached for objects without any difficulty. There was no weakness of the upper or lower extremities. There was no limb ataxia. Reflexes were present but diminished in the upper and lower extremities. The Babinski sign was not present. An ECG demonstrated left-sided ven¬ tricular hypertrophy. Cardiomegaly was noted on chest roentgenogram. Slowing in the left temporal and right frontal and temporal areas was noted on an EEG. Computed tomography (CT) on the third hospital day demonstrated a nonenhancing lucency in the left lateral-ventral thala¬ mus (Figure). A CT scan repeated on the 12th hospital day was unchanged. On the During the patient's hospitalization, the Boston Diagnostic Aphasia Examination (BDAE) was administered. Spontaneous speech was fluent, easily articulated with normal intonation, phrase length, and grammatical form. Moderate to severe auditory comprehension deficits were noted. Word-retrieval problems were man¬ ifested as a lack of content words. Verbal output was characterized by frequent ver¬ bal paraphasias, extended English jargon, and neologisms. Repetition of single words and high-probability sentences was gener¬ ally intact, although occasional phonemic paraphasias were observed. Repetition of low-probability sentences was poor, with frequent neologistic distortion. Reading and writing skills were severely impaired, the BDAE Z-score profile was consistent with transcortical sensory aphasia (Ta¬ ble). The patient was discharged to a nursing home on the 18th hospital day without improvement in her language abilities. Aspirin, dipyridamole, insulin, and diuret¬ ic therapy were prescribed. Three months after discharge, a family member reported that the patient's condi¬ tion had improved substantially. However, she was still "mixed-up" at times. Verbal paraphasias occurred on naming common¬ place objects, eg, an oncoming bus would be identified as a train or car. Reading skills were steadily improving. She was again able to read the newspaper. During the sixth month following hospi¬ talization, the patient was reexamined. She spoke softly, fluently, and spontane¬ ously. Semantic paraphasia was infre¬ quently noted. Writing to dictation was marked by perseveration and poor gram¬ matical construction. She counted back¬ ward from 20 to 18 in 15 s when asked to count from 20 to 0 rapidly. One of three pictured presidents was recalled after five minutes. The other two were identified This case and others from the liter¬ ature suggest that injury to the left thalamus is followed by a constella¬ tion of deficits that may include reduced or fading voice volume, neolo¬ gisms, verbal and phonemic paraphasic errors, laconic speech, contam¬ inations, and intrusions. Repetition is nearly always intact. Comprehension is variably affected. Perseveration is often prominent. Several cases, including our own, have shown unex¬ plained fluctuations in or fatigability of speech performance, ie, deteriora¬ tion of grammatically correct speech into unintelligible jargon. We have divided these deficits into four major clusters: (1) extrapyramidal, (2) lexi¬ cal access, (3) vigilance, and (4) com¬ prehension. Decreased or fading voice volume (extrapyramidal cluster) is common with thalamic injury1·6·19-20 and appears to reflect an elemental speech distur¬ bance rather than an aphasie disor¬ der.18 The anatomic basis for this defect may be interruption of extrapy¬ ramidal inputs into the thalamus. Fibers from the medial globus palli¬ dus and pars reticularis of the sub¬ stantia nigra enter the ansa lenticularis to end in VA nucleus and the rostral portion of VL nucleus.2729 In our case the latter two nuclei were involved. A variety of phenomena that occur after left thalamic injury include decreased spontaneous speech (lacon¬ ic or sparse speech), anomia, verbal paraphasia, neologisms, and jargon, suggesting marked difficulties in lexi- Downloaded From: http://archneur.jamanetwork.com/ by a University of Missouri - St Louis User on 10/02/2013 — cal access. Anatomie areas that may be important in this process include the supplementary motor region, orbital cortex, and anterior insular cortex.3032 The VA nucleus projects to each of these regions. Furthermore, orbitofrontal cortical projections to insular temporal cortex and the amygdala32 give VA nucleus influence over limbic activity that may affect lexical access. Insular connections with supplementary motor area and cortical association areas32 (including supratemporal plane, frontal, pari¬ etal, and occipital regions) may also influence this process. The large numbers of contamina¬ tions, perseverations, semantic para¬ phasias, intrusions, and neologisms emitted by patients with thalamic injury may reflect more than a defect in lexical access. The failure to sup¬ press incorrect, even outrageous, words suggests a prominent defect in self-regulation of speech (vigilance). This defect could account in part for the neologisms, perseverations, and jargon, as well as for the frequent observations of fluctuations in speech performance.7 Others have suspected that the thalamus may play a role in maintaining vigilance. Ojemann24·33 has suggested a specific "alerting" function for the VL nucleus. Similar¬ ly, Luria25 has suggested that altered vigilance may explain quasiaphasic speech disturbances after thalamic injury. Mohr et al7 have speculated that the logorrheic paraphasia and marked speech fluctuations that occur after thalamic injury reflect deregu¬ lation of the cortical surface. Vigilance deficits may reflect inter¬ ruption of inputs from arousal sys¬ tems. The VA nucleus receives inputs from the ascending mesencephalic reticular system via the intralaminar and midline thalamic nuclei, which also project diffusely to the cortex and globus pallidus.34·35 The VA nucleus is also reciprocally connected with intralaminar nuclei29 and the reticular nucleus.36 These connections help account for the characteristics of the nonspecific thalamic system exhibited by this nucleus.37 In physiologic stud¬ ies, VA stimulation evokes wide¬ spread cortical response.3840 The VA is also considered essential for recruit¬ ing response.4041 Comprehension is variably dis¬ turbed in thalamic injury. The ana¬ tomic basis for this defect may reflect dysfunction of those thalamic projec¬ tions also necessary for lexical access. In addition, the VA nucleus has a modulating or driving influence on Broca's area. Disruption of this inter- connection might produce a compre¬ hension defect by an effect on Wer¬ nicke's area via the superior longitu¬ dinal fasciculus.30 The exact neuroanatomical basis for the language deficits following left thalamic infarction remains specula¬ tive. Physiologic and anatomic evi¬ dence suggest that VA nucleus plays a major role. We have proposed that the deficits following dominant lateralventral thalamic injury can be divided into four major clusters. Although it may be argued that these categories are subject to overlap, are too broad in scope, or constitute deficits that are nonspecific, the clusters do help to organize the analysis of deficits fol¬ lowing thalamic injury and do provide a framework for clinical-pathologic correlation. These clusters also em¬ phasize the preservation of repetition skills after thalamic injury. structures, and particularly of the thalamus, in the mechanisms of speech and language. Int J Neuro 1971;8:300-320. 19. 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