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A correlated fluctuation of language and EEG abnormalities in a case of the Landau-Kleffner syndrome
ELSEVIER
Brain & Development 1994; 16:329-34
Case Report
A correlated fluctuation of language and E E G abnormalities in a case of the Landau-Kleffner syndrome Giovanni Lanzi, Pierangelo Veggiotti, Stefano Conte, Enrica Partesana, Cristina Resi
Despite growing interest in the Landau-Kleffner syndrome there have been few reports dealing with language disorders in recent years. The authors present a clinical case of a child with Landau-Kleffner syndrome focusing particulary on the relationship between language disorders and electroencephalographic abnormalities. The authors emphasize that the language disorders primarily affect the receptive sphere and that there seems to be a relationship between abnormalities during sleep with a deterioration in verbal comprehension.
Key words: L a n d a u - K l e f f n e r syndrome; Language characteristic; E E G abnormality; Acquired aphasia; Continuous spike and waves during sleep; Speech disorder
1. INTRODUCTION In 1957, Landau and Kleffner [1] first described a syndrome characterized by acquired aphasia, epileptic abnormalities and epileptic seizures, hypothesizing that the epileptiform activity was responsible for the language disorders. In recent years, the possible direct relationship between language alterations and epileptiform abnormalities has appearred to be rather controversial [2-5]. In fact, various authors hold completely opposing views on the subject [6-10]. Moreover, despite increasing interest in this topic, reports specifically regarding language disorders are rare [11,12]. We present the case of a young girl with L a n d a u Kleffner syndrome, focusing particularly on evolution of language aspects linked to electroencephalographic ( E E G ) abnormalities.
Divisione di Neuropsichiatria Infantile, Fondazione 'Istituto Neurologico C. Mondino' IRCCS, Universith di Pavia, Pavia, Italy Received 17 May 1993; accepted 30 January 1994
Correspondence address: P. Veggiotti, Fondazione 'Istituto Neurologico C. Mondino', Via Palestro 3, 27100 Pavia, Italy. Fax: (39) (382) 380 286. 0387-7604/94/$07.00 © 1994 Elsevier Science B.V. All rights reserved SSDI 0 3 8 7 - 7 6 0 4 ( 9 4 ) 0 0 0 4 2 - V
2. MATERIALS AND METHODS The patient was monitored during periodic examinations from August 1990, to February 1993. Examinations included E E G recordings while awake and during nocturnal sleep as well as audiorecording of spontaneous speech during play, with her mother present. Recordings were registered, a sample of 100 utterances per session collected and the following evaluations were performed: calculation of medium length utterance (MLU) counted in words; assessment of frequency of phonological alterations expressed as a percentage of words in which there were deletions, additions, substitutions or displacements of phonemes. In this assessment grammatical a n d / o r semantic adequacy were not taken into account. A periodic evaluation of verbal comprehension was also begun as soon as this type of test was possible. The authors used a sentence-picture matching task in which the examiner orally presented 77 sentences to the patient [13]. The girl's task was to point out 1 of 4 pictures that most accurately depicted the meaning of the sentence. Since there was a lack of precise normative data, the girl's performance was compared with that of a control group of 25 subjects with age ranging from 4-6.6 years. These steps were taken in order to
G. Lanzi et al. /Brain & Development 1994; 16." 329-34
330
obtain a longitudinal analysis of verbal capacities based not on the clinical picture alone but on pointers which, if possible, could be quantified in some way and which would make it possible to trace more accurately the evolution of the disorder over a period of time. Cognitive development was also assessed using a non-verbal test (Raven's Progressive Matrices).
3. CASE REPORT A girl was born in 1986, after a normal pregnancy, through a physiological delivery. The family history was negative and the psychomotor development was normal.
In January 1990 (3 years 9 months) the child developed rubella. For several days she seemed to be dumb, as she failed to answer when called. Although this problem cleared up spontaneously, in July 1990 (4 years 3 months) following a period in which she had been completely well, in the space of just a few days the child became all but mute, answering only in monosyllables (see section 4). In September 1990 (4 years 5 months) she was admitted to our department. Laboratory and neuroradiological investigations were all normal. Numerous E E G recordings were also performed (Table 1). With the exception of language, the neurological investigation was normal. Therapy with methylprednisolone (1 m g / k g / d a y ) was instigated. As from November 1990 the dosage was reduced to 0.25
Table 1 EEG recordings and language characteristics Awake
Nocturnal sleep
Language characteristics
September 1990 (4 years 5 months)
Background normal, numerous sharp waves in the left temporal region.
Normal sleep activity. Increased frequency sharp waves and slow waves with diffusion but with prevalence in left temporal region, during non-REM sleep.
Absence of structured language. Absence of verbal comprehension.
December 1990 (4 years 8 months)
Same as September 1990.
Slight decrease in abnormalities with respect to September 1990.
Initial recovery of verbal capacities: MLU 1.66; comprehension of some commonly used expressions.
February 1991 (4 years 10 months)
Isolated sharp waves in in left temporal region.
Isolated sharp waves in left and right temporal regions are present independently
Further improvement: use of multi-word utterances (MLU 1.77) with both grammatical and phonological alterations. Verbal comprehension test: 56% correct answers.
July 1991 (5 years 3 months)
Same as September 1990.
Same as September 1990.
Worsening of comprehension while verbal production continues to increase (MLU 2.48).
March 1992 (5 years 11 months)
Background normal without abnormalities.
Absence of abnormalities.
Improved comprehension.
June 1992 (6 years 2 months)
Background normal: sharp waves in the left and right temporal regions and isolated burst of generalized synchronous spike-wave complex.
Increased frequency of sharp waves and slow waves during non-REM sleep.
Severe drop in verbal comprehension in contrast with both improved correct grammatical use and utterance length (MLU 3.22).
November 1992 (6 years 7 months)
Background normal, various bursts of generalized 2.3-4 Hz spike-wave complex with persistence of sharp waves in left temporal region.
Same as June 1992.
Relapse in verbal comprehension without marked changes in production.
February 1993 (6 years 10 months)
Isolated sharp waves and slow waves in left temporal region.
Slight decrease of abnormalities with respect to November 1992.
Partial recovery in comprehension (56% correct answers). Persisting phonological alterations and grammatical difficulties in verbal production.
G. Lanzi et al. / Brain & Development 1994; 16." 329-34
m g / k g / d a y owing to the appearance of side effects. In December 1990 (4 years and 8 months) the child had a first generalized seizure and in April 1991 she had a second generalized toni- clonic seizure. Therapy with VPA (20 m g / k g / d a y ) and clobazam (10 rag/day) was begun. There was a partial recovery of speech until a second relapse in July 1991. In August therapy with methylprednisolone (1 m g / k g / d a y ) was re-instigated. In the period from September 1991 to January 1992 the patient presented a substantial clinical improvement. However, due to the presence of serious side effects, the corticosteroid therapy was suspended. In June, more than 4 months after the suspension of methylprednisolone administration, the child had her third relapse. At the beginning of November, in the wake of a slight improvement, she began to present numerous absence seizures with eyelid myoclonias. These episodes were repeated several times daily for a number of days. They disappeared when methylprednisolone therapy (8 mg per day) was re-instigated. The clinical picture at the last follow-up in February 1993 was characterized by disappearance of the seizures, improvement in the language aspects and reappearance of a Cushing-like aspect. At no time were significant behavioral disorders in evidence and the child's cognitive capacities were always normal.
4. LANGUAGE ASPECT Upon initial observation (September 1990, 4 years and 5 months) the patient's speech was limited to onomatopoeic sounds and syllabic fragments. The girl used facial expressions and gestures to communicate vivaciously. Verbal comprehension was severely reduced: the patient did not answer when called by name and seemed to grasp only extremely simple sentences which, given the situation, were in any case predictable. During the following 5 months, there was a slow, partial recovery of verbal production, with a partial dissociation of quantitative from qualitative aspects of the language. Indeed, at 4 years and 10 months of age with an MLU of 1.77, the verbal predicate and function words were all but absent. It should be pointed out that Italian children with the same MLU (achieved at around 2 years of age) demonstrate "a marked increase in the number of utterances in which the verbal predicate is specifically expressed" and this is accompanied by the advent of function words [14]. There were still problems with the phonological organization of spontaneous language. Errors of substitution were very variable in terms of both type and frequency, however, the patient correctly articulated all the phonemes present in a task involving the repetition
331
M.L.U. 4
2.
Age
4.8 4.10 6.3 6.6 6.6 6.7 6.8 5.11 6
6.2 6.3 6.4 6.6 6.7' 6.10
Fig. 1. Medium length utterance, counted in words.
of isolated syllables. Therefore, the phonological disorder involved selection and combination of phonemes rather than mechanisms of speech articulation. While verbal comprehension had improved, the percentage of correct answers on the comprehension test (56%) was much lower than controls (77%) (Fig. 3). In July 1991 (5 years 3 months), the girl had a relapse. Her mother referred to a severe deterioration in comprehension ("she doesn't receive the words") and difficulty in localizing environmental sounds. She also spoke of episodic "mistakes with words" that seemed to be paraphasic substitutions. The patient was described as alternating fidgety behavior with apathy and sometimes presented episodes of apparently unmotivated aggressiveness. The mother's description was confirmed by clinical testing. The percentage of correct answers on the comprehension test dropped to 40% (Fig. 3) and the girl required use of extralinguistic aids even to comprehend the simplest colloquial language. Nevertheless, apart from previously cited naming difficulties, the deterioration did not seem to involve production. In fact, the patient showed a consistent improvement in MLU (2.48) (Fig. 1), with an initial use of 'expanded' phrase structures [15] (e.g. "questo 6 il fiore della mamma", "this is mommy's flower"). Phonological simplifications were still present. During the following 8 months there was a recovery in verbal comprehension (Fig. 3), and the MLU continued to increase despite occasional fluctuations. In March 1992 (5 years 11 months) the percentage of correct responses on comprehension test was 65% (Fig. 3). MLU, although slightly reduced, confirmed the somewhat positive tendency observed during the entire period under examination (Fig. 1). The situation remained relatively stable until June 1992 (6 years 2 months) with the occurrence of the third relapse with the aforementioned dissociation of production from comprehension: despite the dramatic
332
G. Lanzi et al. / Brain & Det,elopment 1994; 16." 329-34
Frequency 100
% Correct 8nowere 100
80
80 4
~
--q~---
~
~
/
60
40 7
~
l:a
'~
]
40
'~'~
20 ~ 200'
Age
,
,
4.10
6.3
, - - 7 -
6.6
0
Age
4.8 4.10 6.3 6.6 6.6 6.7 6.8 6.11 6
-J'+-
6.2 6.3 6.4 6.6 6.7 6.10
6.11
Patient
~
6.2
~-
6.3
6.4
6.7
6.10
Control group
Fig. 3. Correct responses on comprehension test. Fig. 2. Phonological alterations,
fall in decoding capacities (to the extent that testing was impeded) the girl achieved the highest MLU recorded since the beginning of the study (3.22) (Fig. l). 55% of the utterances consisted of multi-words, with prevalence (64%) of correct grammatical structures. Deterioration in production began a month later (July 1992, 6 years 3 months) with a substantial shortening of MLUs (2.11) (Fig. 1), and a marked increase in phonological simplifications (Fig. 2). Comprehension remained quite limited. In the following 3 months there was a recovery in comprehension (65% correct answers) (Fig. 3) while there was no substantial improvement in MLU and phonological performance. The last relapse was in November 1992 (6 years 7 months): there was another sudden, dramatic drop in decoding capacities without any marked change in production. The most recent data refer to February 1993 (6 years 10 months) and reveal partial recovery in comprehension (56% correct answers) (Fig. 3), and again,
an increase in MLU (2.95), while phonological and grammatical difficulties persisted (Fig. 2).
5. DISCUSSION In order to highlight possible links between E E G and language aspects, a longitudinal study was carried out in which we examined the two factors side by side. At the time of initial medical consultation the patient was already undergoing her first relapse. The E E G recordings while awake (Table 1) were characterized by normal background activity with slow spike and slow wave predominantly involving the left temporal region. There was a marked activation of abnormalities during sleep: this activation, which does not occur in REM sleep, can be likened to a continuous spike and wave during sleep (CSWS). However, it differed from such a situation in three ways: the morphology was different (slow spike followed by slow wave remaining constant); the bilateral, diffuse discharges did not oc-
~pvt_~
Fig. 4. Polygraphic recording during nocturnal sleep: in the left temporal region localized spikes followed by generalized discharges are present. At the end of these, focal slow waves localized to the left hemisphere appear. The physiological sleep patterns are distinguishable.
G. Lanzi et al. /Brain & Development 1994; 16:329-34
cupy at least 85% of slow sleep [16]; the temporal predominance was always marked. Furthermore, it appears significant that during nocturnal sleep, at the end of bilateral discharges there were considerable focal slow waves, which were more marked in the left temporal region (Fig. 4). This E E G pattern has been associated with subjects presenting CSWS and who have been found to have a cerebral lesion or cerebral structural alteration which is, in most cases, focal. (B. Dalla Bernardina, Verona, Italy, unpublished data). Contrary to this, the results of repeated neuroradiological investigations, carried out on our patient over a period of time, were always normal. On the language side, weaknesses emerged in relation to all parameters studied, with comprehension affected earlier and more seriously than production. Even after brief intervals of time there were considerable variations in the degree of impairement of the phonological decoding processes. Only when the disorder was in its most acute phase could the clinical picture be said to resemble that of auditory verbal agnosia, a situation which proved to be extremely transitory. When the patient had her 2nd, 3rd and 4th relapse there was a reccurrence of the E E G abnormalities already recorded in 1990. On the language side, this was accompanied by a clear dissociation of the level of production achieved (which was maintained) from the level of verbal comprehension (which recorded a dramatic drop). These observations prompt several considerations. Our patient had 4 relapses which, in view of reports in the literature [3], is atypical. The appearance of the first symptoms coincided with a viral infection and it is peculiar that the acute phase of disorder appeared to recur with an apparently periodic-type, seasonal frequency. During the relapse phase, numerous immunological investigations were carried out on the serum and cerebrospinal fluid. It was, however, impossible to demonstrate the presence of factors of an autoimmune or infectious nature, a fact which seems partially to contradict recent reports in the literature [17]. Moreover, the clinical picture remained atypical, showing a succession of long periods of improvement and sudden annual relapses. Only the 4th relapse appeared to feature a close link between the language disorder and the worsening of the epilepsy. The relapses can therefore be considered the 'active phase' of the disorder. From a clinical stand-point, they take the form of impairment, first of comprehension and then of production. The clinical situation was always characterized by a marked activation of E E G abnormalities which were predominantly recorded in the temporal region. This feature could suggest bio-
333
electric expression of a central acoustic analyzing dysfunction. The specific and persistent phonological and grammatical difficulties which characterized our patient's verbal production, as well as her difficulties in comprehension, could be put down to such a condition. In line with this hypothesis, we wish to underline that our patient never presented serious behavioral disorders, nor a reduction in cognitive capacities. Furthermore, it should be remembered that the language disorder involved only coding-decoding processes and not pragmatic aspects or content. As well as providing confirmation of the specific nature of language disorder, these considerations suggest that the marked activation of the focal abnormalities without the establishment of a CSWS does not constitute an indication of overall deterioration of cognitive capacities [18]. In conclusion, in our patient, there seems to be link between E E G abnormalities and language difficulties and, in particular, between activation of the temporal abnormalities and involvement of the phonological decoding-coding processes. ACKNOWLEDGMENTS We wish to thank Grazia Papalia and Pietro Marini for technical assistance.
REFERENCES [1] Landau W, Kleffner F. Syndrome of acquired aphasia with convulsive disorder in children. Neurology 1957; 7: 523-30. [2] Deonna T. Acquired epileptiform aphasia in children (LandauKleffner syndrome). J Clin Neurophysiol 1991; 8: 288-98. [3l Beaumanoir A. The Landau-Kleffner syndrome. In: Roger J, Bureau M, Dravet Ch, Dreifuss FE, Perret A, Wolf P, eds. Epileptic syndromes in infancy, childhood and adolescence. 2nd ed. London: Libbey, 1992: 232-44. [4] Nakano S, Okuno T, Mikawa H. Landau-Kleffner syndrome EEG topographic studies. Brain Dec (Tokyo) 1989; 11: 43-50. [5] Landau W. Landau-Kleffner syndrome: an eponymic badge of ignorance. Arch Neurol 1992; 49: 353. [6] Lanzi G, Boiardi A. Illustrazione di un caso di afasia acquisita. Neuropsichiatria Infantile 1970; 206: 135-56. [7] Hirsch E, Marescaux C, Maquet P, et al. Landau-Kleffner syndrome: a clinical and EEG study of five cases. Epilepsia 1990; 31: 756-67. [8] Paquier PF, van Dongen HR, Loonen MCB. The Landau-Kleffner syndrome or 'acquired aphasia with convulsive disorder'. Arch Neurol 1992; 49: 354-9. [9] Perniola T, Margari L, Buttiglione M, Andreula C, Simone II, Santostasi R. A case of Landau-Kleffner syndrome secondary to inflammatory demyelinating disease. Epilepsia 1993; 39: 5516. [10] Solomon GE, Carson D, Pavlakis S, Fraser R, Labar D. Intracranial EEG monitoring in Landau-Kleffner syndrome associated with left temporal lobe astrocytoma. Epilepsia 1993; 34: 557-60. [11] Veggiotti P, Conte S, Partesana E, Viri M, Rapporto tra aspetti verbalied anomalie elettroencefalografiche nella sindrome di Landau-Kleffner. Boll Lega It Epil 1992; 7:211-3. [12] van de Sandt-Koenderman WME, Smit IAC, van Dongen HR,
334
[13]
[14] [15] [16]
G. Lanzi et al. /Brain & Det~elopment 1994; 16:329-34 van Hest JBC. A case of acquired aphasia and convulsive disorder: some linguistic aspects of recovery and breakdown. Brain Language 1984; 21: 174-83. Cipriani P, Chilosi AM, Ciuti A, Pfanner P. La comprensione di strutture linguistiche semplici nei bambini dai 3 anni 6 mesi a 4 anni 6 mesi. Studio preliminare su un campione analizzato con un test a scelta figurata multipla. Giorn Neuropsich Eth EL,ol 1988; 8: 49-59. Chilosi A, Cipriani P. II bambino disfasico. Pisa: Edizioni del Cerro, 1991. Parisi D, Antinucci F. Elementi di grarnmatica. Torino: Boringhieri, 1973. Tassinari CA, Bureau M, Dravet C, Dalla Bernardina B, Roger
J. Epilepsy with continuous spikes and waves during slow sleep otherwise described as ESES (epilepsy with electrical status epilepticus during slow sleep). In: Roger J, Bureau M, Dravet Ch, Dreifuss FE, Perret A, Wolf P, eds. Epileptic syndromes in infancy, childhood, and adolescence. 2nd ed. London: Libbey, 1992: 245-56. [171 Nevsimalova S, Tauberova A, Doutlik S, Kucera V, Dlouha O. A role of autoimmunity in the etiopathogenesis of LandauKleffner syndrome? Brain Dec (Tokyo) 1992; 14: 342-5. [18] Roulet E, Deonna T, Gaillard F, Peter-Favre C, Despland PA. Acquired aphasia, dementia, and behavior disorder with epilepsy and continuous spike and waves during sleep in a child. Epilepsia 1991; 32: 495-503. -
Brain & Development 1994; 16:329-34
Case Report
A correlated fluctuation of language and E E G abnormalities in a case of the Landau-Kleffner syndrome Giovanni Lanzi, Pierangelo Veggiotti, Stefano Conte, Enrica Partesana, Cristina Resi
Despite growing interest in the Landau-Kleffner syndrome there have been few reports dealing with language disorders in recent years. The authors present a clinical case of a child with Landau-Kleffner syndrome focusing particulary on the relationship between language disorders and electroencephalographic abnormalities. The authors emphasize that the language disorders primarily affect the receptive sphere and that there seems to be a relationship between abnormalities during sleep with a deterioration in verbal comprehension.
Key words: L a n d a u - K l e f f n e r syndrome; Language characteristic; E E G abnormality; Acquired aphasia; Continuous spike and waves during sleep; Speech disorder
1. INTRODUCTION In 1957, Landau and Kleffner [1] first described a syndrome characterized by acquired aphasia, epileptic abnormalities and epileptic seizures, hypothesizing that the epileptiform activity was responsible for the language disorders. In recent years, the possible direct relationship between language alterations and epileptiform abnormalities has appearred to be rather controversial [2-5]. In fact, various authors hold completely opposing views on the subject [6-10]. Moreover, despite increasing interest in this topic, reports specifically regarding language disorders are rare [11,12]. We present the case of a young girl with L a n d a u Kleffner syndrome, focusing particularly on evolution of language aspects linked to electroencephalographic ( E E G ) abnormalities.
Divisione di Neuropsichiatria Infantile, Fondazione 'Istituto Neurologico C. Mondino' IRCCS, Universith di Pavia, Pavia, Italy Received 17 May 1993; accepted 30 January 1994
Correspondence address: P. Veggiotti, Fondazione 'Istituto Neurologico C. Mondino', Via Palestro 3, 27100 Pavia, Italy. Fax: (39) (382) 380 286. 0387-7604/94/$07.00 © 1994 Elsevier Science B.V. All rights reserved SSDI 0 3 8 7 - 7 6 0 4 ( 9 4 ) 0 0 0 4 2 - V
2. MATERIALS AND METHODS The patient was monitored during periodic examinations from August 1990, to February 1993. Examinations included E E G recordings while awake and during nocturnal sleep as well as audiorecording of spontaneous speech during play, with her mother present. Recordings were registered, a sample of 100 utterances per session collected and the following evaluations were performed: calculation of medium length utterance (MLU) counted in words; assessment of frequency of phonological alterations expressed as a percentage of words in which there were deletions, additions, substitutions or displacements of phonemes. In this assessment grammatical a n d / o r semantic adequacy were not taken into account. A periodic evaluation of verbal comprehension was also begun as soon as this type of test was possible. The authors used a sentence-picture matching task in which the examiner orally presented 77 sentences to the patient [13]. The girl's task was to point out 1 of 4 pictures that most accurately depicted the meaning of the sentence. Since there was a lack of precise normative data, the girl's performance was compared with that of a control group of 25 subjects with age ranging from 4-6.6 years. These steps were taken in order to
G. Lanzi et al. /Brain & Development 1994; 16." 329-34
330
obtain a longitudinal analysis of verbal capacities based not on the clinical picture alone but on pointers which, if possible, could be quantified in some way and which would make it possible to trace more accurately the evolution of the disorder over a period of time. Cognitive development was also assessed using a non-verbal test (Raven's Progressive Matrices).
3. CASE REPORT A girl was born in 1986, after a normal pregnancy, through a physiological delivery. The family history was negative and the psychomotor development was normal.
In January 1990 (3 years 9 months) the child developed rubella. For several days she seemed to be dumb, as she failed to answer when called. Although this problem cleared up spontaneously, in July 1990 (4 years 3 months) following a period in which she had been completely well, in the space of just a few days the child became all but mute, answering only in monosyllables (see section 4). In September 1990 (4 years 5 months) she was admitted to our department. Laboratory and neuroradiological investigations were all normal. Numerous E E G recordings were also performed (Table 1). With the exception of language, the neurological investigation was normal. Therapy with methylprednisolone (1 m g / k g / d a y ) was instigated. As from November 1990 the dosage was reduced to 0.25
Table 1 EEG recordings and language characteristics Awake
Nocturnal sleep
Language characteristics
September 1990 (4 years 5 months)
Background normal, numerous sharp waves in the left temporal region.
Normal sleep activity. Increased frequency sharp waves and slow waves with diffusion but with prevalence in left temporal region, during non-REM sleep.
Absence of structured language. Absence of verbal comprehension.
December 1990 (4 years 8 months)
Same as September 1990.
Slight decrease in abnormalities with respect to September 1990.
Initial recovery of verbal capacities: MLU 1.66; comprehension of some commonly used expressions.
February 1991 (4 years 10 months)
Isolated sharp waves in in left temporal region.
Isolated sharp waves in left and right temporal regions are present independently
Further improvement: use of multi-word utterances (MLU 1.77) with both grammatical and phonological alterations. Verbal comprehension test: 56% correct answers.
July 1991 (5 years 3 months)
Same as September 1990.
Same as September 1990.
Worsening of comprehension while verbal production continues to increase (MLU 2.48).
March 1992 (5 years 11 months)
Background normal without abnormalities.
Absence of abnormalities.
Improved comprehension.
June 1992 (6 years 2 months)
Background normal: sharp waves in the left and right temporal regions and isolated burst of generalized synchronous spike-wave complex.
Increased frequency of sharp waves and slow waves during non-REM sleep.
Severe drop in verbal comprehension in contrast with both improved correct grammatical use and utterance length (MLU 3.22).
November 1992 (6 years 7 months)
Background normal, various bursts of generalized 2.3-4 Hz spike-wave complex with persistence of sharp waves in left temporal region.
Same as June 1992.
Relapse in verbal comprehension without marked changes in production.
February 1993 (6 years 10 months)
Isolated sharp waves and slow waves in left temporal region.
Slight decrease of abnormalities with respect to November 1992.
Partial recovery in comprehension (56% correct answers). Persisting phonological alterations and grammatical difficulties in verbal production.
G. Lanzi et al. / Brain & Development 1994; 16." 329-34
m g / k g / d a y owing to the appearance of side effects. In December 1990 (4 years and 8 months) the child had a first generalized seizure and in April 1991 she had a second generalized toni- clonic seizure. Therapy with VPA (20 m g / k g / d a y ) and clobazam (10 rag/day) was begun. There was a partial recovery of speech until a second relapse in July 1991. In August therapy with methylprednisolone (1 m g / k g / d a y ) was re-instigated. In the period from September 1991 to January 1992 the patient presented a substantial clinical improvement. However, due to the presence of serious side effects, the corticosteroid therapy was suspended. In June, more than 4 months after the suspension of methylprednisolone administration, the child had her third relapse. At the beginning of November, in the wake of a slight improvement, she began to present numerous absence seizures with eyelid myoclonias. These episodes were repeated several times daily for a number of days. They disappeared when methylprednisolone therapy (8 mg per day) was re-instigated. The clinical picture at the last follow-up in February 1993 was characterized by disappearance of the seizures, improvement in the language aspects and reappearance of a Cushing-like aspect. At no time were significant behavioral disorders in evidence and the child's cognitive capacities were always normal.
4. LANGUAGE ASPECT Upon initial observation (September 1990, 4 years and 5 months) the patient's speech was limited to onomatopoeic sounds and syllabic fragments. The girl used facial expressions and gestures to communicate vivaciously. Verbal comprehension was severely reduced: the patient did not answer when called by name and seemed to grasp only extremely simple sentences which, given the situation, were in any case predictable. During the following 5 months, there was a slow, partial recovery of verbal production, with a partial dissociation of quantitative from qualitative aspects of the language. Indeed, at 4 years and 10 months of age with an MLU of 1.77, the verbal predicate and function words were all but absent. It should be pointed out that Italian children with the same MLU (achieved at around 2 years of age) demonstrate "a marked increase in the number of utterances in which the verbal predicate is specifically expressed" and this is accompanied by the advent of function words [14]. There were still problems with the phonological organization of spontaneous language. Errors of substitution were very variable in terms of both type and frequency, however, the patient correctly articulated all the phonemes present in a task involving the repetition
331
M.L.U. 4
2.
Age
4.8 4.10 6.3 6.6 6.6 6.7 6.8 5.11 6
6.2 6.3 6.4 6.6 6.7' 6.10
Fig. 1. Medium length utterance, counted in words.
of isolated syllables. Therefore, the phonological disorder involved selection and combination of phonemes rather than mechanisms of speech articulation. While verbal comprehension had improved, the percentage of correct answers on the comprehension test (56%) was much lower than controls (77%) (Fig. 3). In July 1991 (5 years 3 months), the girl had a relapse. Her mother referred to a severe deterioration in comprehension ("she doesn't receive the words") and difficulty in localizing environmental sounds. She also spoke of episodic "mistakes with words" that seemed to be paraphasic substitutions. The patient was described as alternating fidgety behavior with apathy and sometimes presented episodes of apparently unmotivated aggressiveness. The mother's description was confirmed by clinical testing. The percentage of correct answers on the comprehension test dropped to 40% (Fig. 3) and the girl required use of extralinguistic aids even to comprehend the simplest colloquial language. Nevertheless, apart from previously cited naming difficulties, the deterioration did not seem to involve production. In fact, the patient showed a consistent improvement in MLU (2.48) (Fig. 1), with an initial use of 'expanded' phrase structures [15] (e.g. "questo 6 il fiore della mamma", "this is mommy's flower"). Phonological simplifications were still present. During the following 8 months there was a recovery in verbal comprehension (Fig. 3), and the MLU continued to increase despite occasional fluctuations. In March 1992 (5 years 11 months) the percentage of correct responses on comprehension test was 65% (Fig. 3). MLU, although slightly reduced, confirmed the somewhat positive tendency observed during the entire period under examination (Fig. 1). The situation remained relatively stable until June 1992 (6 years 2 months) with the occurrence of the third relapse with the aforementioned dissociation of production from comprehension: despite the dramatic
332
G. Lanzi et al. / Brain & Det,elopment 1994; 16." 329-34
Frequency 100
% Correct 8nowere 100
80
80 4
~
--q~---
~
~
/
60
40 7
~
l:a
'~
]
40
'~'~
20 ~ 200'
Age
,
,
4.10
6.3
, - - 7 -
6.6
0
Age
4.8 4.10 6.3 6.6 6.6 6.7 6.8 6.11 6
-J'+-
6.2 6.3 6.4 6.6 6.7 6.10
6.11
Patient
~
6.2
~-
6.3
6.4
6.7
6.10
Control group
Fig. 3. Correct responses on comprehension test. Fig. 2. Phonological alterations,
fall in decoding capacities (to the extent that testing was impeded) the girl achieved the highest MLU recorded since the beginning of the study (3.22) (Fig. l). 55% of the utterances consisted of multi-words, with prevalence (64%) of correct grammatical structures. Deterioration in production began a month later (July 1992, 6 years 3 months) with a substantial shortening of MLUs (2.11) (Fig. 1), and a marked increase in phonological simplifications (Fig. 2). Comprehension remained quite limited. In the following 3 months there was a recovery in comprehension (65% correct answers) (Fig. 3) while there was no substantial improvement in MLU and phonological performance. The last relapse was in November 1992 (6 years 7 months): there was another sudden, dramatic drop in decoding capacities without any marked change in production. The most recent data refer to February 1993 (6 years 10 months) and reveal partial recovery in comprehension (56% correct answers) (Fig. 3), and again,
an increase in MLU (2.95), while phonological and grammatical difficulties persisted (Fig. 2).
5. DISCUSSION In order to highlight possible links between E E G and language aspects, a longitudinal study was carried out in which we examined the two factors side by side. At the time of initial medical consultation the patient was already undergoing her first relapse. The E E G recordings while awake (Table 1) were characterized by normal background activity with slow spike and slow wave predominantly involving the left temporal region. There was a marked activation of abnormalities during sleep: this activation, which does not occur in REM sleep, can be likened to a continuous spike and wave during sleep (CSWS). However, it differed from such a situation in three ways: the morphology was different (slow spike followed by slow wave remaining constant); the bilateral, diffuse discharges did not oc-
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Fig. 4. Polygraphic recording during nocturnal sleep: in the left temporal region localized spikes followed by generalized discharges are present. At the end of these, focal slow waves localized to the left hemisphere appear. The physiological sleep patterns are distinguishable.
G. Lanzi et al. /Brain & Development 1994; 16:329-34
cupy at least 85% of slow sleep [16]; the temporal predominance was always marked. Furthermore, it appears significant that during nocturnal sleep, at the end of bilateral discharges there were considerable focal slow waves, which were more marked in the left temporal region (Fig. 4). This E E G pattern has been associated with subjects presenting CSWS and who have been found to have a cerebral lesion or cerebral structural alteration which is, in most cases, focal. (B. Dalla Bernardina, Verona, Italy, unpublished data). Contrary to this, the results of repeated neuroradiological investigations, carried out on our patient over a period of time, were always normal. On the language side, weaknesses emerged in relation to all parameters studied, with comprehension affected earlier and more seriously than production. Even after brief intervals of time there were considerable variations in the degree of impairement of the phonological decoding processes. Only when the disorder was in its most acute phase could the clinical picture be said to resemble that of auditory verbal agnosia, a situation which proved to be extremely transitory. When the patient had her 2nd, 3rd and 4th relapse there was a reccurrence of the E E G abnormalities already recorded in 1990. On the language side, this was accompanied by a clear dissociation of the level of production achieved (which was maintained) from the level of verbal comprehension (which recorded a dramatic drop). These observations prompt several considerations. Our patient had 4 relapses which, in view of reports in the literature [3], is atypical. The appearance of the first symptoms coincided with a viral infection and it is peculiar that the acute phase of disorder appeared to recur with an apparently periodic-type, seasonal frequency. During the relapse phase, numerous immunological investigations were carried out on the serum and cerebrospinal fluid. It was, however, impossible to demonstrate the presence of factors of an autoimmune or infectious nature, a fact which seems partially to contradict recent reports in the literature [17]. Moreover, the clinical picture remained atypical, showing a succession of long periods of improvement and sudden annual relapses. Only the 4th relapse appeared to feature a close link between the language disorder and the worsening of the epilepsy. The relapses can therefore be considered the 'active phase' of the disorder. From a clinical stand-point, they take the form of impairment, first of comprehension and then of production. The clinical situation was always characterized by a marked activation of E E G abnormalities which were predominantly recorded in the temporal region. This feature could suggest bio-
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electric expression of a central acoustic analyzing dysfunction. The specific and persistent phonological and grammatical difficulties which characterized our patient's verbal production, as well as her difficulties in comprehension, could be put down to such a condition. In line with this hypothesis, we wish to underline that our patient never presented serious behavioral disorders, nor a reduction in cognitive capacities. Furthermore, it should be remembered that the language disorder involved only coding-decoding processes and not pragmatic aspects or content. As well as providing confirmation of the specific nature of language disorder, these considerations suggest that the marked activation of the focal abnormalities without the establishment of a CSWS does not constitute an indication of overall deterioration of cognitive capacities [18]. In conclusion, in our patient, there seems to be link between E E G abnormalities and language difficulties and, in particular, between activation of the temporal abnormalities and involvement of the phonological decoding-coding processes. ACKNOWLEDGMENTS We wish to thank Grazia Papalia and Pietro Marini for technical assistance.
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