Nerve growth factor: relationship to the cyclic AMP system of sensory ganglia.

Nerve growth factor and N(6),O(2)' dibutyryl adenosine 3',5'-monophosphate both stimulate neurite elongation by explanted ganglia. However, the addition of nerve growth factor does not lead to increased amounts of adenosine 3',5'-monophosphate in intact ganglia, nor does it stimulate adenylate cyclase activity in broken ganglia cells.

Developmental dyslexia. Evidence for a subgroup with a reversal of cerebral asymmetry.

The computerized brain tomograms of 24 patients with developmental dyslexia were analyzed for cerebral asymmetry. Ten patients showed a reversal of the pattern of asymmetry regularly observed in normal right-handed individuals so that the right parietooccipital region was wider than the left. The ten dyslexic patients with this reversal of cerebral asymmetry had a lower mean verbal IQ than the other 14 dyslexic patients in this study. The reversal of cerebral asymmetry that occurred in ten of the dyslexic patients may result in language lateralization to a cerebral hemisphere that is structurally less suited to support language function and thus act as a risk factor for the development of reading disability.

Predictors of survival in clinically diagnosed Alzheimer's disease and multi-infarct dementia.

Duration of survival from time of first evaluation was studied in 61 patients with clinically diagnosed Alzheimer's disease (senile dementia of the Alzheimer type [SDAT]) and 34 patients with clinically diagnosed multi-infarct dementia (MID). Duration of survival did not differ significantly between MID and SDAT. However, since MID patients were younger at onset, MID patients had a lower life quotient than SDAT patients. Race, sex, and age at onset were not predictive of survival in SDAT. History of hypertension, elevated systolic blood pressure, lower scores on tests of Block Designs, and Logico-Grammatical Comprehension predicted shorter survival in SDAT. Age at onset and race were not predictive of survival in MID. Male sex, lower educational attainment, as well as low scores on tests of Logico-Grammatical Comprehension, Digit Span, Naming, Verbal Fluency, and receptive vocabulary, predicted shorter survival in MID.

Aphasia after left thalamic infarction.

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.

Thalamic stroke. Presentation and prognosis of infarcts and hemorrhages.

Thalamic strokes in 62 patients selected from the Stroke Data Bank were studied to determine differences among 18 infarctions (INF), 23 localized hemorrhages (ICH), and 21 hematomas with ventricular extension (IVH). Stupor or coma at onset occurred more frequently in the IVH (62%) than in the INF (6%) or ICH (13%) groups and was reflected in significantly lower median Glasgow Coma Scores in the IVH group (7) than in the INF (15) and ICH (14) groups. Although ocular movements were more frequently abnormal in the IVH group compared with the ICH and INF groups, no significant differences were found in the frequency of motor or sensory deficits. Among the 62 strokes, 32 had restricted lesions of the posterolateral (n = 9), anterior (n = 3), paramedian (n = 7), and dorsal (n = 13) portions of the thalamus. Differences in consciousness and in motor, sensory, and oculomotor deficits were found among the topographic subgroups. Stroke-related deaths occurred in 52% of IVH cases, 13% of ICH cases, and no cases of INF. Median lesion volume as detected with computed tomography was greater in hemorrhages (INF, 2 cm3; ICH, 10 cm3; IVH, 16 cm3), with mortality related to increasing hematoma size. Coma, Glasgow Coma Score lower than 9, weakness score greater than 15 of a possible 30, abnormal ocular movements, and fixed pupils were also associated with stroke-related mortality. We conclude that the initial neurologic syndrome does not discriminate infarcts from intrathalamic hemorrhages. Ventricular extension, however, causes significantly more severe deficits and higher mortality.

Caudate infarcts.

Eighteen patients had caudate nucleus infarcts (10 left-sided; 8 right-sided). Infarcts extended into the anterior limb of the internal capsule in 9 patients, and also the anterior putamen in 5 patients. Thirteen patients had motor signs, most often a slight transient hemiparesis. Dysarthria was common (11 patients). Cognitive and behavioral abnormalities were frequent, and included abulia (10 patients), agitation and hyperactivity (7 patients), contralateral neglect (3 patients, all right caudate), and language abnormalities (2 patients, both left caudate). The majority of patients had risk factors for penetrating artery disease. Branch occlusion of Heubner's artery, or perforators from the proximal anterior or middle cerebral arteries were the posited mechanism of infarction.

Interobserver reliability in the interpretation of computed tomographic scans of stroke patients.

Interobserver reliability in interpretation of computed tomographic images was studied by six senior neurologists who independently evaluated on a standardized Stroke Data Bank form the brain lesions of 17 patients. The results analyzed with kappa statistics yielded moderate to substantial agreement on most items of interest including the stroke pathology and anatomy. In general, the levels of agreement were as high as previously reported for the diagnosis of the mechanism of the stroke, and much higher than on many stroke history items and items of neurologic examination. Excellent agreement was obtained for the detection of infarcts and intracerebral hemorrhage, and substantial agreement was obtained on whether the computed tomographic images were normal or indicative of small deep infarcts, superficial and deep infarcts, and aneurysms. The level of agreement on anatomy of the lesions was best for the frontal, parietal, and temporal lobes, putamen, cerebellum, and subarachnoid space. Implications for clinical research and diagnosis are discussed.

Interobserver agreement in the diagnosis of stroke type.

Interobserver agreement is essential to the reliability of clinical data from cooperative studies and provides the foundation for applying research results to clinical practice. In the Stroke Data Bank, a large cooperative study of stroke, we sought to establish the reliability of a key aspect of stroke diagnosis: the mechanism of stroke. Seventeen patients were evaluated by six neurologists. Interobserver agreement was measured when diagnosis was based on patient history and neurologic examination only, as well as when it was based on results of a completed workup, including a computed tomographic scan. Initial clinical impressions, based solely on history and one neurologic examination, were fairly reliable in establishing the mechanism of stroke (ie, distinguishing among infarcts, subarachnoid hemorrhages, and parenchymatous hemorrhages). Classification into one of nine stroke subtypes was substantially reliable when diagnoses were based on a completed workup. Compared with previous findings for the same physicians and patients, the diagnosis of stroke type was generally more reliable than individual signs and symptoms. These results suggest that multicentered studies can rely on the independent diagnostic choices of several physicians when common definitions are employed and data from a completed workup are available. Furthermore, reliability may be less for individual measurements such as signs or symptoms than for more-complex judgments such as diagnoses.

Interobserver variability in the assessment of neurologic history and examination in the Stroke Data Bank.

Interobserver reliability in obtaining neurologic histories and examinations was investigated among neurologists collaborating in the Stroke Data Bank (SDB). Seventeen in-hospital stroke patients were examined by six neurologists experienced in stroke over the course of three days. Patients were examined twice a day for two successive days, with each patient seen by four different neurologists. Data were recorded on SDB forms, according to definitions and procedures established for the SDB. Percent agreement and kappa coefficients were calculated to assess the levels of agreement for each item. Important differences in levels of agreement were found among items on both neurologic history and examination. Agreement among neurologists was higher for neurologic examination than for history. Patterns of agreement for items with low prevalence or with numerous unknown ratings are discussed. Improvement in interobserver agreement due to data editing for intra-observer consistency was shown.

Behavioral abnormalities after right hemisphere stroke.

We evaluated 41 patients with unilateral right hemisphere strokes for hemiparesis, hemianopia, constructional apraxia, neglect, extinction, unilateral spatial neglect on drawing (USND), dressing apraxia, anosognosia, prosopagnosia, and motor impersistence. Low correlations were found among USND, neglect, and extinction. Constructional apraxia showed a higher correlation with USND than with hemianopia. Motor impersistence and anosognosia correlated with the severity of the hemiplegia. Left neglect, motor impersistence, and anosognosia tended to occur only with large strokes. Injury to the right parietal lobe appears to be an important determinant of USND and constructional apraxia. In most cases of motor impersistence, left neglect, and anosognosia, there was injury to the right parietal lobe and also to structures beyond the parietal lobe. In two cases, small deep lesions produced behavioral abnormalities comparable to those of larger superficial cortical lesions.

Recovery of behavioral abnormalities after right hemisphere stroke.

We studied recovery of function in 41 patients with right hemisphere stroke. Recovery was rapid for left neglect, prosopagnosia, anosognosia, and unilateral spatial neglect on drawing (USN). Recovery was slower for h mianopia, hemiparesis, motor impersistence, and extinction. Rates of recovery were intermediate for constructional apraxia and dressing apraxia. Sex had no influence on the rate of recovery. Younger patients recovered from prosopagnosia more rapidly than older patients. Patients with smaller lesions recovered more quickly from anosognosia, USN, and hemiparesis than patients with larger lesions. Patients with hemorrhages recovered more rapidly from constructional apraxia, neglect, and motor impersistence than patients with infarcts. Recovery of function and the factors influencing recovery can by studied systematically by life table methods.

Acquired learning disability for reading after left temporal lobe damage in childhood.

A 6-year-old boy developed hemorrhage in the left temporal lobe and subsequently underwent left temporal lobectomy. Afterwards, he was completely unable to learn to read or write. Psychological tests showed impairment in verbal learning and memory, with right ear and right visual field superiority in verbal perception. A Wada test showed no aphasia after right carotid injection. We conclude that damage to the speech-dominant temporal lobe resulted in the inability to learn to read or write. Despite the lesion, speech remained strongly lateralized to the left hemisphere, accounting for the right-sided advantage in verbal perception. Some patients with developmental dyslexia may have dysfunction of a strongly dominant left hemisphere rather than a delay or incompleteness of language lateralization.

Headache in acute cerebrovascular disease.

Headache features were compared in 51 patients with acute subarachnoid hemorrhage (SAH), 61 with intraparenchymal hemorrhage (IPH), and 160 with ischemic stroke (IS). SAH patients had more sentinel headaches, more onset headaches, and more bilateral and severe onset headaches than patients with IPH or IS. Vomiting with onset headache was more common in SAH and IPH. In stepwise logistic regression analysis, onset headache and vomiting were direct predictors of SAH, but were inversely related to IS. Sentinel headache was not a predictor of underlying stroke mechanism. The data suggest that some headache features are more frequently associated with particular stroke subtypes and that onset headache and vomiting may be important indicators of stroke mechanism.

Fungal infections of the central nervous system: comparative analysis of risk factors and clinical signs in 57 patients.

Risk factors and clinical manifestations of fungal infections of the CNS were analyzed in 57 autopsied patients. Aspergillosis occurred in 16, candidiasis in 27, and cryptococcosis in 14. Nine of 31 variables studied showed significant difference (p less than 0.01). Cryptococcosis was community-acquired in 93%; whereas, aspergillosis and candidiasis were nosocomial in more than 95%. Focal neurologic deficits developed in 50% with CNS aspergillosis, but in only 4% with candidiasis. Meningeal signs occurred in 86% with CNS cryptococcosis, but in only 6% with aspergillosis and 7% with candidiasis. Discriminant analysis demonstrated that CNS aspergillosis was most frequently a nosocomial infection with focal neurologic deficits, pulmonary infiltrates, and hypercortisolemia. Cryptococcosis was generally a non-nosocomial infection with meningeal signs presenting in an ambulatory population. CNS candidiasis was a clinically occult nosocomial fungal infection with generally no deficits or meningismus, occurring most frequently in the neonate, the elderly, and surgical patients. The discriminant functions, which correctly classified 91% of these CNS fungal infections, may be applicable in clinical diagnosis.

Ischemic strokes are more severe in Poland than in the United States.

Case fatality rates for stroke were ascertained prospectively in two regional catchment hospitals in Poland and 36 teaching hospitals in the US University Hospital Consortium. Case fatality rates in Poland (23.9%) were higher than in the United States (7.5%). Angina, atrial fibrillation, and congestive heart failure were more frequent in Polish stroke patients (40%, 26%, and 25%, respectively) than in US patients (17%, 12%, and 10%). Stroke severity as indicated by higher frequencies of hemiplegia, disordered consciousness, dysphagia, and aphasia was greater in Poland (19%, 39%, 28%, and 42%, respectively) than the United States (11%, 13%, 14%, and 26%).

Familial amentia, unusual ventricular calcifications, and increased cerebrospinal fluid protein.

A sibship originally reported by Friedman and Roy as showing severe mental retardation, strabismus, hyperactive tendon reflexes, lalling speech, and foot deformities was restudied. Three major additional findings were noted. The cerebrospinal fluid protein concentration was increased two to three times above normal in four siblings who were available for study. Radiographs of cranial structures in three siblings showed identical pathologic intracranial calcifications which correspond in distribution to the choroid plexus. The choroid plexus was not demonstrable in one patient when radiolabeled 99m-Tc-pertechnetate was injected without perchlorate. Neuropathologic findings in one sibling included small subcortical heterotopias and atrophy of the choroid plexus with encasement by glial fibrils. These findings denote a new heredofamilial neurologic syndrome associated with mental retardation and a disorder of choroid plexus.

Weekly alcohol consumption, cigarette smoking, and the risk of ischemic stroke: results of a case-control study at three urban medical centers in Chicago, Illinois.

To assess the role of current weekly alcohol consumption as a risk factor for cerebral infarction, we administered a pretested questionnaire to 205 middle-aged and elderly acute ischemic stroke patients and 410 outpatient controls matched by age, sex, race, and method of hospital payment. The frequency of hypertension (p less than 0.001) and transient ischemic attacks (p = 0.051), and mean weekly alcohol consumption (p = 0.0286) and mean pack-years cigarette exposure (p = 0.0168) were higher among stroke index cases than controls. For weekly alcohol consumption and mean pack-years cigarette exposure, there was a highly significant dose-response effect. In analyses to assess the possibility of mutual confounding effects of independent variables, we found hypertension and smoking to be independent risk factors for ischemic stroke, while alcohol consumption was not. Separate analyses by sex yielded similar results. We conclude that current weekly alcohol consumption may not be an independent risk factor for cerebral infarction in middle-aged and elderly patients.

Occlusive disease of the middle cerebral artery.

We studied 20 patients with severe occlusive disease of the mainstem middle cerebral artery (MCA) or its major division branches, and 25 patients with internal carotid artery (ICA) disease. MCA disease patients were more often black, female, younger, and had fewer TIAs than the ICA disease patients. Neurologic signs in patients with MCA disease evolved progressively during days to weeks, whereas ICA disease patients more often had an acute onset of nonprogressive deficits. CT commonly showed restricted subcortical or wedge-shaped infarcts in MCA disease patients. All MCA disease patients had stroke, but 40% of ICA disease patients had no infarction. MCA lesions usually affected the mainstem MCA or its major superior division. Patients with MCA disease seldom had recurrent ischemia in the same vascular territory as the stroke and had a low incidence of subsequent cardiac death.

Racial differences in the distribution of anterior circulation occlusive disease.

We compared clinical and angiographic features of 26 white and 45 black patients with symptomatic occlusive cerebrovascular disease. White patients had more transient ischemic attacks, carotid bruits, and more severe occlusive disease of the internal carotid artery origin. Blacks had more severe disease of the middle cerebral artery stem and supraclinoid internal carotid arteries. Differences were not explained by racial differences in the prevalence of hypertension, diabetes, hypercholesterolemia, or ischemic heart disease. Since the middle cerebral artery lesions in blacks do not correlate with other accepted epidemiologic, clinical, and laboratory markers of atherosclerosis, the lesions may arise from a disorder that differs from atherosclerosis.

Brain infarction severity differs according to cardiac or arterial embolic source.

We compared clinical and radiologic features between 246 cardiac embolism (EMB) and 66 arterial embolic (tandem arterial pathology [TAP]) patients selected from the 1,273 patients with cerebral infarction in the Stroke Data Bank. Diagnostic definitions accounted for the increased frequency of cardiac disease among patients with EMB compared with TAP (78.4% versus 29.3%), while transient ischemic attacks (32.3% versus 13.1%) and carotid artery bruit (15.1% versus 3.3%) were more prevalent in TAP than in EMB. Multiple logistic regression differentiated TAP and EMB further. The probability of a TAP diagnosis was increased by the CT finding of a superficial infarct alone (odds ratio [OR] = 4.6; 95% CI = 1.5 to 13.7) or by a higher admission hematocrit. The probability of EMB was greater in patients with an initial decreased consciousness (OR = 39.2; 95% CI = 4.0 to 381.3) or with an abnormal first CT (OR = 3.2; 95% CI = 1.2 to 8.6). These findings indicate that the two infarct subtypes differ in the location and extent of the cortical infarction, which argues for a smaller particle size, with smaller and more distal infarction in embolism from an arterial source compared with cardiogenic embolism.