A case of primary progressive aphasia. A 14-year follow-up study with neuropathological findings.

Primary progressive aphasia has been clinically defined as a progressive language deficit leading to the dissolution of almost all language functions with relative preservation of other cognitive functions until late in the course of the disease. Two types of language impairment have been described for primary progressive aphasia, which differ with respect to the degree of fluency of spontaneous speech. Whereas some authors have emphasized non-fluency as a defining characteristic of primary progressive aphasia, others have proposed that phonemic rather than semantic paraphasias in naming, both in the fluent and the non-fluent subtype, should be used as a criterion to distinguish primary progressive aphasia from slowly progressive aphasia in other forms of degenerative brain disease. Patients with fluent speech and semantic dementia, as typically seen in Alzheimer's disease, produce semantic paraphasias and circumlocutions rather than phonemic errors in naming. This paper reports the long-term follow-up of a patient with fluent aphasic speech, whose language profile over a decade was similar to that of patients with semantic dementia. Neuropathological examination revealed no evidence of Alzheimer's disease. Pick's disease or Pick variant, but showed spongiform changes of cortical layers (II and III) in temporal and, less severely, in frontal gyri. The present case indicates that semantic dementia is not a reliable indicator of probable Alzheimer's disease and supports the notion that there are different subtypes of primary progressive aphasia which cannot be defined by fluency or by the presence of phonemic paraphasia. Progress in identifying the neuropathological correlates of these subtypes in cases with lobar atrophy and spongiform changes should be expected from hereditary variants of progressive disorder.

Piracetam as an adjuvant to language therapy for aphasia: a randomized double-blind placebo-controlled pilot study.

OBJECTIVE: To determine whether piracetam 4.8 g/day together with intensive language therapy improved language function more than language therapy alone. DESIGN: Double-blind, placebo-controlled parallel group study. SETTING: Referral speech and language clinic of a university department of neurology. PATIENTS: Sixty-six inpatients with aphasia present between 4 weeks and 36 months. INTERVENTIONS: Intensive language therapy for 6 weeks in all patients. Thirty-two patients received piracetam 4.8 g daily and 34 patients received placebo. MAIN OUTCOME MEASURE: The Aachen Aphasia Test (AAT), a standardized procedure for evaluating the severity of aphasia, was performed at baseline and after 6 weeks' treatment. RESULTS: In 50 patients evaluated for efficacy, a trend toward improvement in the active group was observed in all subtests of the AAT. This trend was statistically significant for absolute differences in recovery of "written language" and "profile level." CONCLUSION: Piracetam appears to have a positive adjuvant effect on the recovery of aphasia in patients receiving intensive language therapy.

To what extent can aphasic syndromes be localized?

Modern views on the representation of function in the cortex make it difficult to maintain the notion that specific subtypes of aphasia are associated with specific centres within the language area. We have conducted a retrospective study on 221 aphasic patients with one contiguous vascular lesion in the territory of the middle cerebral artery. The localization of CT lesions was established within a standardized grid model. Aphasiological data were based on one or more examinations with the Aachen Aphasia Test. Both sets of data were processed in a data- and methodbase system. No unequivocal association between type of aphasia and localization of lesion was found. In a smaller study, participation of basal ganglia and in particular of the head of the caudate nucleus in lesions producing aphasia was not confirmed. Concepts of the localization of a lesion in aphasia must account for changes in patterns of aphasic symptoms in the presence of a stable lesion and for the impact of the neurological condition that has produced the lesion.

Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke.

An open angiography-based, dose rate escalation study on the effect of intravenous infusion of recombinant tissue plasminogen activator (rt-PA) on cerebral arterial recanalization in patients with acute focal cerebral ischemia was performed at 16 centers. Arterial occlusions consistent with acute ischemia in the carotid or vertebrobasilar territory in the absence of detectable intracerebral hemorrhage were prerequisites for treatment. After the 60-minute rt-PA infusion, arterial perfusion was assessed by repeat angiography and computed tomography scans were performed at 24 hours to assess hemorrhagic transformation. Of 139 patients with symptoms of focal ischemia, 80.6% (112) had complete occlusion of the primary vessel at a mean of 5.4 +/- 1.7 hours after symptom onset. No dose rate response of cerebral arterial recanalization was observed in 93 patients who completed the rt-PA infusion. Middle cerebral artery division (M2) and branch (M3) occlusions were more likely to undergo recanalization by 60 minutes than were internal carotid artery occlusions. Hemorrhagic infarction occurred in 20.2% and parenchymatous hematoma in 10.6% of patients over all dose rates, while neurological worsening accompanied hemorrhagic transformation (hemorrhagic infarction and parenchymatous hematoma) in 9.6% of patients. All findings were within prospective safety guidelines. No dose rate correlation with hemorrhagic infarction, parenchymatous hematoma, or both was seen. Hemorrhagic transformation occurred significantly more frequently in patients receiving treatment at least 6 hours after symptom onset. No relationship between hemorrhagic transformation and recanalization was observed. This study indicates that site of occlusion, time to recanalization, and time to treatment are important variables in acute stroke intervention with this agent.

An early description of slowly progressive aphasia.

Slowly progressive aphasia without generalized dementia has become an important issue of present-day neuropsychological research. Historically, credit for the first description is usually given to Pick. Another German-speaking author who has published a vivid description of a pertinent cases is Pick's contemporary, Max Rosenfeld. This author has also observed a patient with slowly progressive spatial disorientation and visual recognition deficit, and he has discussed these patients in a remarkably modern way in the context of partial atrophy of the brain.

Outcome of intensive language treatment in aphasia.

Sixty-eight aphasic inpatients received intensive language treatment (9 hr per week over a period of 6-8 weeks). Outcome was assessed by means of the Aachen Aphasia Test (AAT), a standardized test battery for the German language. For patients with duration of aphasia up to 12 months, amount of improvement was corrected by the expected rate of spontaneous recovery as determined by a previous multicenter follow-up study. About two thirds of the patients showed significant improvement in AAT performance according to psychometric single case analysis procedures. A similar rate of improvement was found for individuals with chronic aphasia beyond the stage of spontaneous recovery.

Slowly progressive aphasia in three patients. The problem of accompanying neuropsychological deficit.

Three patients are described presenting with a slowly progressive aphasic disorder associated with degenerative cortical disease. The symptoms began in the presenium and the length of illness was 4 to 5 years. The language disorder corresponded in all patients to a severe form of amnesic aphasia but a moderate to marked semantic breakdown was also found. Formal language examination was complemented by extensive neuropsychological testing. This revealed a severe deficit in language-dependent cognitive tasks. The patients were given a follow-up language and neuropsychological examination. In addition to the deterioration of language functions, a significant decline was observed in nonverbal intelligence tasks even though their level of performance still remained within the normal range. Follow-up with standardized intelligence tests might detect a trend towards generalized dementia in similar cases. This would mean that these patients should be considered as presenting with slowly progressive aphasia preceding generalized dementia.

Intraarterial thrombolytic therapy in acute stroke.

Intraarterial thrombolytic therapy by means of urokinase has proved to be effective and safe in certain instances of acute thromboembolic occlusion of the vertebral and/or the basilar artery. Small hemorrhages have not led to deterioration in the patients' neurological state. In the territory of the carotid artery local thrombolytic therapy may be effective in very selected cases of acute thromboembolic occlusion. There is a high risk of intracerebral hemorrhage. Possibly intravenous administration of tPA will replace local intraarterial thrombolysis, provided a strict regimen is established for selection of patients, determination of dosage and time constraints for the application of this therapy.

The clinical examination for motor apraxia.

The signs and symptoms of motor apraxia are described both for ideomotor and ideational apraxia. Typical errors are described. For ideomotor apraxia a list of tasks is given. The many conceptual and psychometric problems that still await an answer are briefly discussed.

Analysis of prosody in the spontaneous speech of patients with CV-recurring utterances.

We report a study on 9 patients with global aphasia whose language production was restricted to chains of one and the same recurring CV syllable. Length of utterance was determined by the number of syllables between two pauses and major length types were used for pitch analysis. By means of a tonetic method the pitch level of syllables was transcribed so that pitch variations could be established. Our findings contradicted the clinical impression that these patients can convey communicative intentions by means of a variety of fluently produced intonation contours. Even though all patients had a considerable inventory of length types they predominantly used only one or two of them. Pitch types were found to be similarly stereotypical. As an explanation for the fluently produced CV utterances with stereotypical length and pitch, the assumption of iterative motor mechanisms underlying CV speech production was rejected in favour of preserved automatic speech processing and abolished controlled processing.

Non-invasive diagnosis of intracranial lesions in the vertebrobasilar system. A comparison of Doppler sonographic and angiographic findings.

The accuracy and the reliability of extracranial vertebral Doppler flow (continuous wave Doppler sonography) for the detection of intracranial vertebrobasilar lesions was studied prospectively in twenty-one patients with brainstem disturbances and/or coma. The Doppler findings were compared with cerebral angiography. Doppler sonography was highly reliable for both detection and exclusion of high grade intracranial vertebrobasilar lesions. The pathognomonic Doppler finding was an abrupt deceleration of the blood column during systole and stoppage or even reflux during diastole. The same blood flow alterations were found in two additional illustrative cases having therapeutically or brain-death induced blockages of the vertebral arteries. The pathophysiologic mechanisms of flow disturbances and the limitations of Doppler sonography in this area are discussed.

A new method in computer-assisted imaging in neuroanatomy.

A procedure is described yielding computed images of postmortem brains with high topographic accuracy. Structures of the brain are traced and registered by means of a digitizer capable of measuring coordinates three-dimensionally. The information corresponding to one brain model is stored on a flexible disk with a capacity of 256 Kbytes. According to the output desired, the resulting brain images are either completely or partially displayed on the computer screen as stereo pairs. The brain models possess a local fidelity of about 1 mm. The images are useful in simultaneously studying superficial and central parts of the brain, spatial relationships of the various structures and the projection of deep structures onto the surface of the brain. A RAM of about 100 Kbytes is necessary for a program enabling the user to perform stereo projections, three-dimensional transformations and other image manipulations. The special features of anatomical computer imaging as compared to computed tomography (CT) and nuclear magnetic resonance imaging (NMR) are outlined. A combination of these different techniques seems to improve clinical diagnosis.