Multiple Sclerosis Cognition Abstracts - 2

  1. Language functions in incipient Cognitive decline in MS
    J Neurol Sci 1996 Sep 15;141(1-2):79-86

  2. Cognitive function in Primary/Progressive and Transitional/Progressive Multiple Sclerosis: A controlled study with MRI correlates
    Brain 1999 Jul;122(Pt 7):1341-1348

  3. Primary and Transitional/Progressive MS: A clinical and MRI cross-sectional study
    Neurology 1999 Mar 10;52(4):839-45

  4. Serial NeuroPsychological assessment and MRI analysis in Multiple Sclerosis
    Arch Neurol 1997 Aug;54(8):1018-25

  5. Executive function in Multiple Sclerosis: The role of Frontal Lobe pathology
    Brain 1997 Jan;120 ( Pt 1):15-26

  6. The progress of Cognitive decline in Multiple Sclerosis: A controlled 3-year follow-up
    Brain 1997 Feb;120 ( Pt 2):289-97

  7. Brain MRI correlates of Cognitive Impairment in Primary and Secondary/Progressive Multiple Sclerosis
    J Neurol Sci 1995 Oct;132(2):222-7

  8. Brain MRI correlates of Cognitive Impairment in Multiple Sclerosis
    J Neurol Sci 1993 Apr;115 Suppl:S66-73

  9. MRI measures and their relations with clinical disability in Relapsing/Remitting and Secondary/Progressive Multiple Sclerosis
    Mult Scler 1997 Aug;3(4):221-5

  10. Brain and Spinal Cord abnormalities in Multiple Sclerosis: Correlation between MRI parameters, clinical subtypes and symptoms
    Brain 1998 Apr;121 ( Pt 4):687-97

  11. Correlation between Brain MRI lesion volume and disability in Multiple Sclerosis
    Acta Neurol Scand 1996 Aug;94(2):93-6

  12. Cognitive Impairment in early-onset Multiple Sclerosis: Pattern, predictors, and impact on everyday life in a 4-year follow-up
    Arch Neurol 1995 Feb;52(2):168-72

  13. NeuroPsychological, NeuroRadiological and Clinical findings in Multiple Sclerosis: A Three Year Follow-Up Study
    Eur J Neurol 1998 May;5(3):283-286


#1

Language Functions In Incipient Cognitive Decline In Multiple Sclerosis

Kujala P, Portin R, Ruutiainen J
J Neurol Sci 1996 Sep 15;141(1-2):79-86
Masku Neurological Rehabilitation Centre, Finland
PMID# 8880697; UI# 97035041
Abstract

Although the mechanisms of Cognitive Impairment in Multiple Sclerosis (MS) have been extensively studied, evaluation of Language Functions has been given little attention.

In the present study, we evaluated whether impairment of Language Functions is associated with Cognitive decline in MS. We studied Naming, Reading, and Writing performance of two carefully matched patient groups differing only with respect to Cognitive status.

In Language tasks, the patients with incipient Cognitive decline not only demonstrated performance slowness but also made more errors than the patients with preserved Cognitive capacity and the healthy controls.

The Comprehensive Naming Error analysis revealed that the Cognitively deteriorated patients produced error types not present in the other two study groups.

Contrary to previous suggestions, the present study indicates that impaired Language performances in MS are attributable to mild Cognitive deterioration rather than to Sensory or Motor factors.

Thus, assessment of Language Functions should be included in NeuroPsychological evaluations of MS patients.
#2

Cognitive Function In Primary/Progressive And Transitional/Progressive Multiple Sclerosis:
A Controlled Study With MRI Correlates

Camp SJ, Stevenson VL, Thompson AJ, Miller DH, Borras C, Auriacombe S, Brochet B, Falautano M, Filippi M, Herisse-Dulo L, Montalban X, Parrcira E, Polman CH, De Sa J, Langdon DW
Brain 1999 Jul;122(Pt 7):1341-1348
Institute of Neurology, Dept of Clinical Neurology, London, UK; Hospitals Vall d'Hebron, Unitat de NeuroImmunologia Clinica, Barcelona, Spain; Hopital Pellegrin, Service de Neurologie, Bordeaux, France; Scientific Institute, Ospedale San Raffaeke, Dept of NeuroScience, Milan, Italy; Hospital de Santa Maria, Servico de Neurologia, Lisbon; Portugal Univ Hospital; Free University, Amsterdam, Netherlands
PMID# 10388799
Abstract

The relative rarity of Primary/Progressive (PP) and Transitional/Progressive (TP) Multiple Sclerosis has meant that little documentation of Cognitive function in such patients is currently available.

The aim of this study was to investigate the Cognitive skills of patients with PP and TP Multiple Sclerosis relative to matched healthy controls, and to examine the relationship of this impairment to MRI parameters.

Sixty-three patients (43 PP, 20 TP) were individually matched with healthy controls, who undertook the same Cognitive tasks as the patient group.

The NeuroPsychological assessment comprised Rao's brief repeatable battery, a reasoning test, and a measure of Depression. Patients also underwent T1- and T2-weighted Brain MRI.

These patients were taken from a larger cohort (158 PP, 33 TP) in whom it had been demonstrated that there were no significant differences between the mean scores of the PP and TP groups on any of the Cognitive variables.

The 63 patients were therefore taken as one group for comparison with the healthy controls. These patients performed significantly worse than the controls in tests of Verbal Memory, Attention, Verbal Fluency and Spatial Reasoning.

An impairment index was constructed and applied to the patient data. This correlated modestly with T2-lesion load (r = 0.45, P = 0.01), T1-HypoIntensity load (r = 0.45, P = 0.01) and Cerebral volume (r = -0.35, P = 0.01).

Thus, PP and TP Multiple Sclerosis patients demonstrate significant Cognitive dysfunction when compared with matched healthy controls.

The relationship between this impairment and MRI parameters is moderate, suggesting that Cognitive dysfunction in PP and TP Multiple Sclerosis has a complex and multifactorial Etiology, which is not adequately explained by pathology as demonstrated on conventional MRI.
#3

Primary And Transitional/Progressive MS:
A Clinical And MRI Cross-Sectional Study

Stevenson VL, Miller DH, Rovaris M, Barkhof F, Brochet B, Dousset V, Dousset V, Filippi M, Montalban X, Polman CH, Rovira A, de Sa J, Thompson AJ
Neurology 1999 Mar 10;52(4):839-45
Institute of Neurology, NMR Research Unit, London, UK
PMID# 10078736; UI# 99176622
Abstract

Background
Ten percent of patients with MS have a Progressive course from onset with no history of relapses or remissions.

A smaller subgroup follow a similar Progressive course but have a single relapse at some point (Transitional/Progressive [TP] MS). To date these patients have been excluded from receiving licensed treatments for MS and from most therapeutic trials.

Objective
To document the clinical and MRI characteristics of a large cohort of Progressive patients, including 158 with Primary/Progressive (PP) MS and 33 with TPMS.

Data from a small reference group of 20 patients with Secondary/Progressive (SP) MS are also presented for reference.

Methods
Patients were recruited from six European centers. All underwent a clinical assessment including scoring on the Expanded Disability Status Scale (EDSS) and MRI of the Brain and Spinal Cord.

Results
The men-to-women ratio was 81:77 (51% men) in the PP group, 14:19 (42% men) in the TP group, and 5:15 (25% men) in the SP group.

The mean age at disease onset was significantly higher in the PP group than it was in the other two groups (PP 40.2 years, TP 34.9 years, SP 28.7 years).

On MRI the PP group had lower mean Brain T2 and T1 HypoIntensity lesion loads than the SP group (T2 12.02 versus 27.74 cm3, p = 0.001; T1 4.34 versus 7.04 cm3, p = 0.015).

The SP and TP cohorts had significantly more T2-weighted lesions in the Spinal Cord than the PP patients, and the SP cohort had the greatest degree of Atrophy.

There was a correlation in the PP and TP patients between EDSS score and Brain and Spinal Cord Atrophy (r = 0.3, 0.2, p < or = 0.006) but not with Brain lesion load.

The PP and TP patients who presented with Spinal Cord pathology had significantly lower Brain T2 and T1 lesion loads than those with Non-Spinal Cord presentations (p = 0.002).

Conclusions
The monitoring of disease progression in PPMS is difficult, although measures of Atrophy correlate with the EDSS and appear most promising.

This study increases our understanding of this unique patient group, which will be further expanded with the acquisition of serial data.
#4

Serial NeuroPsychological Assessment And MRI Analysis In Multiple Sclerosis

Hohol MJ, Guttmann CR, Orav J, Mackin GA, Kikinis R, Khoury SJ, Jolesz FA, Weiner HL
Arch Neurol 1997 Aug;54(8):1018-25
Brigham and Women's Hospital, Center for Neurologic Diseases, Boston, MA 02115, USA
PMID# 9267977; UI# 97411864
Abstract

Objective
To assess the correlation between Cognitive dysfunction and disease burden in Multiple Sclerosis (MS) during a 1-year period.

Design
The Brief, Repeatable Battery of NeuroPsychological Tests in Multiple Sclerosis was performed at entrance and 1 year.

Patients underwent at least 20 Proton Density (range, 20-24) and T2-weighted axial Magnetic Resonance Imaging (MRI) Brain scans except for stable patients who were scanned monthly.

Magnetic Resonance Imaging was evaluated using computer-automated, 3-dimensional volumetric analysis.

Setting
A research clinic of a university hospital.

Patients
Forty-four patients with MS of the following disease categories: Relapsing/Remitting (14), Relapsing/Remitting Progressive (12), Chronic/Progressive (13), and stable (5).

Main Outcome Measures
The relationships between scores on the Brief, Repeatable Battery of NeuroPsychological Tests in Multiple Sclerosis and 2 MRI measures (total lesion volume and Brain to IntraCranial cavity volume ratio) were assessed using linear regression.

These MRI measures were also compared with Cognitive status at 1 year using analysis of variance.

Results
Overall, there was no decline in mean Cognitive test performance during 1 year.

Significant correlations were found between baseline NeuroPsychological test scores of NonVerbal Memory, Information-Processing Speed, and Attention and both MRI measures.

Patients with Chronic/Progressive MS demonstrated the strongest correlations. At 1 year, change in Information-Processing Speed and Attention correlated with change in total lesion volume.

The mean increase in total lesion volume was 5.7 mL for 4 patients whose Cognitive status worsened compared with 0.4 mL for 19 patients who improved and 0.5 mL for 21 patients who remained stable.

Conclusions
During a 1-year period mean Cognitive performance did not worsen.

Automated volumetric MRI measures of total lesion volume and Brain to IntraCranial cavity volume ratio correlated with NeuroPsychological performance, especially in patients with Chronic/Progressive MS.

Worsening MRI lesion burden correlated with Cognitive decline.
#5

Executive Function In Multiple Sclerosis:
The Role Of Frontal Lobe Pathology

Foong J, Rozewicz L, Quaghebeur G, Davie CA, Kartsounis LD, Thompson AJ, Miller DH, Ron MA
Brain 1997 Jan;120 ( Pt 1):15-26
Institute of Neurology, London, UK
PMID# 9055794; UI# 97208852
Abstract

Deficits in executive function and the relationship to Frontal lesion load as detected on MRI were investigated in 42 Multiple Sclerosis patients.

A battery of NeuroPsychological test examining executive skills including computerized tests of Planning and Spatial Working Memory was administered to all subjects.

Performance on these tests was impaired in the patient group when compared with a group of matched controls, but not all executive skills were affected to the same extent.

Although a number of executive test scores correlated with the severity of Frontal lesion load, it was difficult to disentangle the specific contribution of Frontal Lobe pathology to the impairment on Executive Tasks.

This study highlights the difficulties in attempting to attribute specific Cognitive abnormalities to focal Brain pathology in the presence of widespread disease such as in Multiple Sclerosis.
#6

The Progress Of Cognitive Decline In Multiple Sclerosis:
A Controlled Three Year Follow-Up

Kujala P, Portin R, Ruutiainen J
Brain 1997 Feb;120 ( Pt 2):289-97
Masku Neurological Rehabilitation Centre, Masku, Finland
PMID# 9117376; UI# 97232099
Abstract

The purpose of this study was to illustrate how Cognitive functioning evolves over time in patients with Multiple Sclerosis.

We followed the evolution of Cognitive performances in two clinically and demographically similar Multiple Sclerosis groups, the 'Cognitively preserved' (n = 20) and the 'Cognitively mildly deteriorated' (n = 22), and in healthy controls (n = 34).

We conducted the follow-up examination using the Mild Deterioration Battery, the Mini-Mental State Examination, and a set of additional NeuroPsychological measures after an interval of 3 years.

The drop-out rate in our study was only 5%. The 'Cognitively preserved' Multiple Sclerosis group showed substantial NeuroPsychological stability by performing as well as the controls both at baseline and at follow-up.

By contrast, the initially 'Cognitively mildly deteriorated' group demonstrated Progressive Cognitive decline on many NeuroPsychological tests.

The intermediate-length screening battery, the Mild Deterioration Battery, was sensitive to this decline, whereas the briefer Mini-Mental State Examination was not. The Progressive Cognitive decline could not be predicted from other disease variables.

The study demonstrated that intact Cognitive functioning in Multiple Sclerosis may remain stable, whereas incipient Cognitive decline seems to be widespread and Progressive in nature.

Thus, Progressive Cognitive deterioration should be considered as one of the characteristics of Multiple Sclerosis.
#7

Brain MRI Correlates Of Cognitive Impairment In Primary & S/P Multiple Sclerosis

Comi G, Filippi M, Martinelli V, Campi A, Rodegher M, Alberoni M, Sirabian G, Canal N
J Neurol Sci 1995 Oct;132(2):222-7
Univ of Milan, Scientific Institute, Ospedale San Raffaele, Dept of Neurology, Italy
PMID# 8543952; UI# 96098615
Abstract

Brain Magnetic Resonance Imaging (MRI) and an extensive battery of NeuroPsychological tests exploring Frontal functions, Short and Long-Term Memory, Visuo-Spatial Skills, Attention and Language were applied to 14 patients with Primary/Progressive Multiple Sclerosis (PPMS) and 17 patients with Secondary/Progressive MS (SPMS).

Patients with PPMS and SPMS did not differ in degree of physical disability, but Cognitive deficits were found in 9/17 (53%) patients with SPMS and in only 1/14 (7%) of those with PPMS (p = 0.01).

Patients with SPMS had higher total (p = 0.004), PeriVentricular (p = 0.008) and Non-PeriVentricular (p = 0.04) MRI lesion loads than patients with PPMS.

In detail, patients with SPMS had greater involvement of Frontal (p = 0.05) and Occipital (p = 0.02) Horns, Trigones (p = 0.04), Third Ventricle (p = 0.03), Basal Ganglia (p = 0.02), Parietal (p = 0.02), Temporal (p = 0.004) and Occipital (p = 0.03) lobes.

Patients with SPMS and NeuroPsychological deficits had higher Non-PeriVentricular lesion loads than patients with SPMS who did not have such deficits (p = 0.005).

Our results indicate that both NeuroPsychological and Brain MRI abnormalities are more extensive in patients with SPMS.

Since physical disability was similar for both groups, disability in PPMS may be predominantly due to Spinal Cord involvement.
#8

Brain Magnetic Resonance Imaging Correlates Of Cognitive Impairment In Multiple Sclerosis

Comi G, Filippi M, Martinelli V, Sirabian G, Visciani A, Campi A, Mammi S, Rovaris M, Canal N
J Neurol Sci 1993 Apr;115 Suppl:S66-73
Univ of Milan, Multiple Sclerosis Center, Ospedale S. Raffaele, Italy
PMID# 8340796; UI# 93340689
Abstract

We evaluated the correlations between Cognitive Impairment, clinical and Brain Magnetic Resonance Imaging (MRI) findings in 100 patients with Multiple Sclerosis (MS).

The performance on one or more NeuroPsychological tests was abnormal in 47% of the 64 patients who completed the entire NeuroPsychological battery; the Cognitive Impairment was mild in 14 (22%) and severe in 16 (25%).

Performance on any single NeuroPsychological test was unrelated to clinical parameters (age, duration of the disease, disability).

The NeuroPsychological performance of Relapsing/Remitting patients was better than in patients with a Chronic/Progressive disease.

The mean scores for almost all the NeuroPsychological tests were significantly lower in patients with severe Ventricular dilatation and Corpus Callosum Atrophy than in patients in whom these structures were little affected.

Mean scores for WMS, performance Intelligence Quotient (IQ), total IQ and Token Test (TT) were also significantly correlated with the widening of Cortical Sulci and total lesional scores.

Our data support the contention that the involvement of pathways that are critical for a given Cognitive process as well as the progression of the Axonal degeneration and sclerosis seem to play important roles in the PathoPhysiology of Cognitive Dysfunction in MS.
#9

MRI Measures And Their Relations With Clinical Disability In Relapsing/Remitting And Secondary/Progressive Multiple Sclerosis

Giugni E, Pozzilli C, Bastianello S, Gasperini C, Paolillo A, Koudriavtseva T, Frontoni M, Farina D, Bozzao L
Mult Scler 1997 Aug;3(4):221-5
Univ La Sapienza of RomeDept of Neurological Sciences, Italy
PMID# 9372503; UI# 98039772
Abstract

To further evaluate the relationship between clinical disability and Magnetic Resonance Imaging (MRI) lesion burden, we examined 85 patients with Clinically Definite Multiple Sclerosis (54 Relapsing/Remitting and 31 Secondary/Progressive).

This cross-sectional study reports on the correlations between total and InfraTentorial lesion volume on both T1 and T2 weighted images, and overall physical disability measured by Expanded Disability Status Scale, Ambulation Index and individual Functional Systems.

Assessment of the HypoIntense lesion load on T1 weighted images rather than the HyperIntense lesion load on T2 weighted images at Brain MRI was shown to be useful for differentiating Relapsing/Remitting from Secondary/Progressive Multiple Sclerosis.

A weak relationship between disability and total lesion volume on both T1 and T2 weighted images was found in Relapsing/Remitting Multiple Sclerosis.

In Secondary/Progressive Multiple Sclerosis, InfraTentorial lesion volume on T2 weighted images represents the only marker of disability.

Finally, the presence of Cerebellar, BrainStem and mental impairment was significantly associated to a greater total lesion volume on MRI, while no relationship was found with other functional systems.
#10

Brain And Spinal Cord Abnormalities
In Multiple Sclerosis: Correlation Between MRI Parameters, Clinical Subtypes And Symptoms

Nijeholt GJ, van Walderveen MA, Castelijns JA, van Waesberghe JH, Polman C, Scheltens P, Rosier PF, Jongen PJ, Barkhof F
Brain 1998 Apr;121 ( Pt 4):687-97
Vrije Universiteit Hospital, Dept of Radiology, Amsterdam, The Netherlands
PMID# 9577394; UI# 98238255
Abstract

We investigated various Magnetic Resonance MRI parameters for both Brain and Spinal Cord to see if any improved the ClinicoRadiological correlation in Multiple Sclerosis.

    Ninety-one Multiple Sclerosis patients were imaged using Conventional T1, Proton Density- and T2-weighted MRI of the Brain and Spinal Cord
      • 28 Relapsing/Remitting
      • 32 Secondary/Progressive
      • 31 Primary/Progressive

Focal Brain and Spinal Cord lesion load was scored, as were diffuse signal abnormalities, Brain Ventricular volume and Spinal Cord cross-sectional area.

Clinical measures included the Expanded Disability Status Scale (EDSS), the Functional Systems score and a dedicated Urology complaint questionnaire.

Secondary/Progressive patients differed from Relapsing/Remitting and Primary/Progressive patients by a larger number of HypoIntense T1 lesions in the Brain, Ventricular enlargement and Spinal Cord Atrophy.

Primary/Progressive patients more often had diffuse abnormalities in the Brain and/or Spinal Cord than did Relapsing/Remitting and Secondary/Progressive patients.

In the entire study population, EDSS correlated with both Brain and Spinal Cord MRI parameters, which were independent. The Urological complaint score correlated only with Spinal Cord MRI parameters.

In Relapsing/Remitting and Secondary/Progressive Multiple Sclerosis, the correlation between MRI and clinical parameters was better than in the entire population.

In this subgroup EDSS variance could be explained best by T1 Brain lesion load, Ventricle volume and Spinal Cord cross-sectional area.

In the Primary/Progressive subgroup the ClinicoRadiological correlation was weak for Brain parameters but was present between Spinal Cord symptoms and Spinal Cord MRI parameters.

In conclusion, the different Brain and Spinal Cord MRI parameters currently available revealed considerable Heterogeneity between clinical subtypes of Multiple Sclerosis.

In Relapsing/Remitting and Secondary/Progressive Multiple Sclerosis both Brain and Spinal Cord MRI may provide a tool for monitoring patients, while in Primary/Progressive Multiple Sclerosis the ClinicoRadiological correlation is weak for Brain imaging.
#11

Correlation Between Brain MRI Lesion Volume And Disability In Multiple Sclerosis

Mammi S, Filippi M, Martinelli V, Campi A, Colombo B, Scotti G, Canal N, Comi G
Acta Neurol Scand 1996 Aug;94(2):93-6
Univ of Milan, Scientific Institute, Ospedale S. Raffaele, Dept of Neurology, Italy
PMID# 8891052; UI# 97046130
Abstract

In this study we evaluated the relationships between clinical variables and lesion volumes measured from Magnetic Resonance Imaging (MRI) scans in a large cohort of Multiple Sclerosis (MS) patients.

    One hundred and thirty patients with MS entered the study
  • 36 patients had Relapsing/Remitting (RR)
  • 39 Benign (B)
  • 42 Secondary/Progressive (SP)
  • 13 Primary/Progressive (PP)

There was a significant correlation (r = 0.3; p = 0.0006) between the total lesion load and the EDSS score when the whole cohort of patients was considered.

This correlation increased (r = 0.5) when only patients with RRMS and SPMS were considered. Our data indicate that a correlation between disability and MRI lesion volume in MS exists, but its strength is moderate.
#12

Cognitive Impairment In Early-Onset Multiple Sclerosis Pattern, Predictors, And Impact On Everyday Life
In A 4-Year Follow-Up

Amato MP, Ponziani G, Pracucci G, Bracco L, Siracusa G, Amaducci L
Arch Neurol 1995 Feb;52(2):168-72
Univ of Florence, Dept of Neurology, Italy
PMID# 7848126; UI# 95150856
Abstract

Objectives
To assess the evolution of Cognitive dysfunction in early-onset Multiple Sclerosis, to identify clinical predictors of mental decline, and to determine its impact on a patient's everyday life.

Design
The Cognitive performance of 50 patients with Multiple Sclerosis on a NeuroPsychological battery was compared with that of 70 control subjects initially and again after a 4-year interval.

Clinical predictors of Cognitive Impairment and its effect on daily life were analyzed by stepwise linear regression.

Setting
The research clinic of a university department of Neurology.

Participants
A consecutive sample of 50 inpatients and outpatients with Multiple Sclerosis (mean disease duration, 1.58 years) and 70 demographically matched healthy control subjects selected from the patients' relatives and friends.

Main Outcome Measures
Mean psychometric test scores of both groups at the initial and follow-up testing.

Regression coefficients measuring the relationship between clinical parameters and Cognitive capacity and between mental decline and performance of common tasks measured by the Environmental and the Incapacity Status scales.

Results
Multiple Sclerosis-related deficits in Verbal Memory and Abstract Reasoning on initial testing remained more or less stable on the retest, at which time Linguistic disturbances on the Set and Token tests also emerged.

A patient's initial disability level predicted decreased performance on only four of 13 Cognitive variables, and disease duration did so on only two.

Extent of intellectual decline on initial testing, initial disability level, and Progressive course were independent determinants of handicap in a patient's work and social activities.

Conclusions
Cognitive and Neurological Deficits appear not to develop in parallel. Yet Cognitive dysfunction proves to be a predictor of handicap in everyday life, even in patients in the incipient phase of Multiple Sclerosis.
#13

NeuroPsychological, NeuroRadiological And Clinical Findings In MS: A Three Year Follow-Up Study

Patti F, Failla G, Ciancio MR, L'Episcopo MR, Reggio A
Eur J Neurol 1998 May;5(3):283-286
Istituto di Scienze Neurologiche, Servizio di Neuroriabilitazione e Sclerosi Multipla, Policlinico dell'Universita di Catania, viale Andrea Doria 6, 95125 Catania, Catania, Italy
PMID# 10210843
Abstract

Cognitive Impairment is a frequent feature in Multiple Sclerosis patients. To assess its evolution in comparison with clinical and NeuroRadiological evolution, we followed up 57 Multiple Sclerosis patients over a 3-year period.

During this time EDSS deteriorated significantly but not the MRI lesional load nor the Cognitive test performance.

Nevertheless, both at the beginning and at the end of the follow-up NeuroPsychological results showed a significant correlation with both EDSS and lesional load.

No clinical or paraclinical features could reliably predict NeuroPsychological evolution.

Copyright Lippincott-Raven Publishers

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