Primary progressive aphasia: analisys of 16 cases

METHOD

Sixteen patients were studied, whose demographic data are presented in Table 1. Language evaluation was performed using Montreal-Toulouse (BETA version) 22 and Boston Diagnostic Aphasia Examination (BDAE) 23 protocols, with patients classified as fluent and nonfluent. Seven patients were evaluated longitudinally. The remaining cognitive functions were evaluated using the Mini-Mental State Examination (MMSE) 24 and complementary neuropsychological tests. Cranial MRI was performed on all patients. Ten patients were also submitted to single photon emission computerized tomography (SPECT).

RESULTS

Our series comprised nine females and seven males, with ages varying between 39 and 83 years (average 62.8 years) and an educational level between two and 20 years (average 10.7 years). Six patients spoke other languages besides Portuguese (see Table 1). Neuropsychological evaluation results are shown in Table 2. Performance in language tests, repeated after a one to two year interval in seven cases, is presented in Table 3. Neuroimaging exam results are described in Table 4.

.igure 1 shows a comparison in language performances between fluent and nonfluent groups. .igures 2 and 3 show the speech characteristics profile scales for each group and its evolution over time. These profiles are useful in identifying similarities and differences between fluent form and Brocas aphasia (.ig 2) or between nonfluent form and Wernickes aphasia (.ig 3). .igures 4 and 5 illustrate the neuroimaging (SPECT and MRI) findings in a fluent and a nonfluent patient, respectively. These figures include speech samples from the same patients.

Differential diagnosis and evolution of cases

The clinical course, although restricted in some cases, can cast further light on the differential diagnosis between correlate syndromes such as semantic dementia, as observed in case 14. In this case, the familys report on the progression of linguistic changes suggests steady reduction, and their first description approached transcortical motor aphasia. Oral comprehension began worsening three years after the disease had manifested, where aspects most preserved were word repetition and reading. The patients evolution showed marked comprehension difficulties, which differentiates it from a typical anterior cerebral lesion profile. In this case, one can speculate on the presence of semantic dementia (given that the familys description of language reduction was somewhat vague). This hypothesis does not persist given the verification of a residual comprehension capacity, aptitude for isolated words in naming tests and also evidenced by the ability to treat information semantically when visual stimuli were supplied, such as in reading tests. Besides, there were no difficulties in manipulating objects.

Neuroimaging

Considering the MRI findings, we noted that 15 patients in our series presented predominant left hemisphere atrophy. In three cases (2, 4 and 16), the atrophy was bilateral, although predominant in the left side. The temporal region was the most affected, with atrophy present in 11 cases; one with temporo-parietal atrophy (Case 6), two with fronto-temporal atrophy (Cases 15 and 16) and one with volumetric reduction of left hippocampus (Case 5). Perisylvian atrophy was reported in three cases (1, 7 e 8), thus implying frontal and/or temporal degeneration (these cases are considered separately because we can not describe the site of anomaly accurately). One case (13) presented diffuse cortical and subcortical atrophy.

Regarding perfusion studied with SPECT, of the 13 patients that underwent the exam, ten presented CB. abnormalities in the left hemisphere only. Bilateral CB. abnormalities existed in Cases 4, 13 and 16, being focal in two cases (4 and 16) and generalized in one (13). In eight cases, the temporal region was the most affected, being isolated in one case (2), or associated with frontal (Cases 3 and 14), parietal (Cases 7, 10 and 16) or fronto-parietal (cases 5 and 12). Three patients had homogeneous left fronto-temporo-parietal CB. abnormalities (Cases 6, 11 and 15). The perfusion abnormalities were more pronounced than those found in MRI, both in extension and intensity.

DISCUSSION

Our results disclosed different and peculiar patterns of language impairment among the patients, to be expected, especially considering the differing progressions of the disease over time. The anatomical distribution of abnormalities in neuroimaging is similar to that described in literature .

The first possible consideration, analyzing language data, is including these cases in the classical aphasic syndromes. Using generic taxonomy, we chose to divide the cases into fluent and nonfluent and to identify the isolated aphasic symptoms, given that one of the difficulties in regard to classification, stems from the fact that the patients were diagnosed when the intensity, combination and sum of alterations surpassed the classical aphasic syndrome definitions. The attempt to recoup evolution from clinical history provided by family proved unsuccessful, given the overlapping interpretations of memory and language alterations, exemplified by frequent indications of word forgetting for anomia, or the generic descriptions of pronunciation alterations.

As new cases of PPA were being described, it became evident that the clinical features are complex and heterogeneous. This has led several authors to attempt a classification of the patients into subgroups with similar clinical characteristics. One of the first attempts was to categorize into nonfluent (where expression alterations such as agrammatism, emission reduction and phonologic alterations predominate) and fluent, where the semantic impairment is more evident. One of the most intriguing discussions arises from similarities and differences that may exist between fluent PPA and semantic dementia 25,26 . In the latter condition, however, the impairment of cognition seems to be more prevalent, affecting the recognition of words and objects, traits usually associated with bilateral temporal lobe dysfunction.

The subdivision into nonfluent and fluent groups proved insufficient to include all new data observed by researchers. Principally due to the overlapping of symptoms between patients in both groups, as well as features shared by PPA and other degenerative diseases with lobar atrophy, such as frontotemporal dementia (.TD) 27,25 . The existence of pathologic alterations that are present both in .TD and PPA reinforces the hypothesis of both manifestations representing a non-Alzheimer degenerative process, with the occurrence of a different distribution of the pa- Impairment of lexical access in a fluent patient (case 6) P My apartment has 3 rooms has a... has a big living room, has a big sacada with a...churrasqueira that is to keep Argentine habits. It has a kitchen, it has a small room for breakfeast and also when we are alone we use it as...as...to have lunch and dinner...

The words in italic refer to names that the patient couldnt access in his mother tongue (Spanish) and were spoken in Portuguese.

Agrammatism found in a nonfluent patient (case 15) Illustrations sequence: in this story, a woman leaves her car with two children inside. The children start driving and the car crashes in a lamppost. Patients description: car guide womun (woman) car exits womun car break fall car fall break the boy guide aumobile (automobile) womun.. (unintelligible).. count (crash) pasts (posts) womun beak (break)

.ig 5. Case 15 -SPECT and MRI showing mild hypoperfusion and atrophy in left fronto-temporal region thological process, either predominantly in the frontal or temporal lobes. Due to this overlapping of clinical and pathological characteristics, Kertesz et al. 28,29 proposed the term Pick complex to include the clinical conditions currently described as .TD, PPA, Picks disease and corticobasal degeneration.

Weintraub and Mesulam 30 proposed a classification of degenerative dementia based on four clinical profiles, each in turn having more probability of association with a specific cerebral disease. This classification takes into account the neuropsychological profile exhibited by the patient during the first two years of disease. PPA is one of these profiles (Progressive Language Network Syndrome).

In our series, it was not possible to classify the patients into classical aphasic syndromes, although a resemblance to predominantly frontal dysfunction (agrammatism), or temporal (marked comprehension disturbances) is admissible. That said, symptoms also described in dementia occurred alongside the language primary deficit.

Regarding fluency, which is a referential for subgroup identification, we did not notice any remarkably positive characteristics, such as hyper fluency. Reduction in fluency and quantitative emission predominated, and were shared by the patients with clinical symptoms compatible with both frontal and temporal dysfunction. Absence of language production occurred when extra-language cognitive symptoms intensified. Anomia was the earliest and most notable symptom, being present in all patients. Disturbances of repetition were also frequent and could be found in the fluent and nonfluent groups.

We can notice in .igures 2 and 3 that the nonfluent group presents greater similarities to Brocas aphasia profile as the disease evolves, except for comprehension, which is more impaired in our data. In the fluent group, independent of evolution time, the profile is more akin to that found in Wernickes aphasia, except for the occurrence of fewer semantic paraphasias in language production.

One of the main goals in the research field of degenerative cerebral diseases is to find a method with enough specificity to allow the elaboration of a prognosis, bearing in mind the great number of years necessary to reach a clinical diagnosis with reasonable acuity. Toward this goal, several groups have striven to establish relations between perfusion and neuroimaging, and the probable clinical evolution for each profile. Talbot et al. 31 described the correlation between standard perfusion with SPECT in 363 patients studied prospectively for 3 years. They found positive correlation between the presence of posterior bilateral alterations and Alzheimers disease, and between anterior bilateral alterations and .TD. Other perfusion patterns, such as patchy distribution and generalized or unilateral (anterior or posterior) alterations, showed less correlation and therefore were less useful for the characterization of a diagnosis.

Neuroimaging findings in PPA keep certain correlation with the clinical variant. In nonfluent cases, there is left frontal and perisylvian atrophy in cranial CT and MRI, with CB. abnormalities in the same areas in SPECT. In fluent cases, the cortical atrophy and CB. abnormalities are located predominantly in the left temporal lobe, hippocampus and parahippocampal gyrus 32 . In a review article of 112 cases, Westbury and Bub 33 found the following distribution: of 59 cases that performed PET or SPECT, 39 (66.1%) had CB. abnormalities exclusively in the left hemisphere and 18 (30.5%) had bilateral CB. abnormalities; perfusion was normal only in two cases (3.4%). In the left hemisphere, for 27.3% of cases the CB. abnormalities were located in the fronto-temporal region, 21.2% in the temporal region, 12.1% in the frontal region, and the remaining 39.4% were distributed between frontal, temporal and parietal lesions combined. In those cases for which MRI was performed (105), 49 (46.7%) had atrophy in the left side only, 38 (36.2%) had bilateral atrophy and in 17 (16.2%) the exams were normal.

The anatomical distribution found in our cases was similar to that documented in literature, namely: predominance in the left hemisphere and, within this, in the temporal and frontal regions or combination of the two. We observed that the abnormalities were more apparent in SPECT than in MRI findings, generally showing areas of CB. abnormalities that were larger and more evident than those seen in MRI. We think this feature of SPECT might be helpful, especially in the earlier stages of the disease when MRI shows only mild diffuse atrophy or asymmetry of Sylvian fissures, in providing a useful clue for correct diagnosis.

CONCLUSION

We found elements in our series that suggest the need to seek an analysis model for the clinical picture of PPA. We think that the description of symptomatology from a longitudinal and cross-sectional point of view is very important to improve our ability to diagnose PPA in its initial phase. Moreover, it will allow refinement of the tools used to identify the symptoms that are typical of this phase. .urthermore, this description can aid to identification of those symptoms that overlap in language disorders and other cognitive losses. Regarding the neuroimaging exams, we believe that SPECT is a valuable instrument in guiding the differential diagnosis, as well as in making useful clinical and anatomical correlations.

RE.ERENCES