Language impairments and CNS infections: a review

Figures & data

Table 1. Studies reporting language impairments due to brain infection.

Type	Agent	Reference	Participant(s)	Neurological damage	Language tests	Main findings
Meningitis	Bacterial (meningococcus, pneumococcus, and haemophilus influenzae)	Pentland et al. (2000)	30 English-speaking children (4 pneumococcal, 26 haemophilus influenzae; 9–11 years old, assessed ~2 years after time of illness)	Not specified	Linguistic knowledge (CELF-3; Semel et al., 1995); Discourse ability (TLC-E; Wiig & Secord, 1989)	Below normal scores in linguistic knowledge, particularly, sentence assembly; and below normal scores in discourse ability, particularly understanding ambiguous sentences, making inferences, recreating sentences, and figurative language
	Bacterial (meningococcus, pneumococcus)	De Beek et al. (2002)	76 Dutch-speaking adults (25 meningococcal, 26 pneumococcal, 25 controls; 16–65 years old; assessed ~1 year after time of illness)	Not specified	Reading irregular words (DART; Schmand & Lindeboom, 1992); Category fluency (animals and jobs); Letter fluency (3 letters, not specified)	No differences between groups in reading irregular groups; people with pneumococcal meningitis scored lower than people with meningococcal and controls in category and letter fluency
	Bacterial (meningococcus, pneumococcus)	Weisfelt et al. (2006)	137 Dutch-speaking adults (49 meningococcal, 38 pneumococcal; 16–65 years old; 50 controls; assessed ~3 months after time of illness)	Not specified	Reading irregular words (DART; Schmand & Lindeboom, 1992); Category fluency (animals and jobs); Letter fluency (3 letters, not specified); Object naming (BNT; Kaplan et al., 1983)	No differences between groups in reading irregular words, category/letter fluency, or object naming
	Bacterial (meningococcus, pneumococcus) and viral (not specified)	Schmidt et al. (2006)	149 German-speaking adults (59 bacterial meningitis, 59 viral meningitis, 30 controls; 30–60 years old, assessed ~6 years after time of illness)	Brain swelling (24%) and ischaemic lesions (10%), only in people with bacterial meningitis	Letter fluency (P, M, K; Aschenbrenner et al., 2000); Category fluency (animals, foods, jobs; Aschenbrenner et al., 2000); Comprehension of spoken instructions (Aachen Aphasia test, Token Test; Huber et al., 1983)	No differences between groups in letter fluency. People with bacterial and viral meningitis scored lower than controls in category fluency, and people with bacterial meningitis scored lower than controls in comprehension of spoken instructions
	Viral (enterovirus, myxovirus, varicella zoster, unidentified)	Sittinger et al. (2002)	42 German-speaking adults (21 viral meningitis; 21 controls; 22–53 years old, assessed ~2 years after time of illness)	5 of 21 people with viral meningitis showed parenchyma involvement	Reciting the alphabet (WAIS-III; Dahl, 1986); Lexical decision (in each item 1 word and 4 non-words are presented – e.g., nesa, naso, nose, nosa; MWT-B, Lehrl, 1995); Verbal concept formation (identify conceptual similarities between two words, WAIS-II; Dahl, 1986)	No differences between people with viral meningitis and controls in any of the tests
Encephalitis	Bacterial (Streptococcus intermedius)	Khaja et al. (2017)	1 English-speaking female (72-year-old, assessed “few days” after complaints)	Left temporal lobe	Naming of a real object “stethoscope”, forward and backward spelling of the word “world”, qualitative spontaneous speech interview	Responded “football” when asked to name the real object “stethoscope”; able to spell forward; one error spelling backward. Spontaneous speech fluent and coherent
	Bacterial (Streptococcus anginosus)	Jimenez et al. (2018)	1 English-speaking female (46-year-old, assessed on hospital admission)	Left thalamic mass, pressure on left lateral ventricle, third ventricle, and hypothalamus	Naming and repetition	Impaired naming and repetition
Encephalitis	Bacterial (treponema pallidum)	Ahn et al. (2012)	1 Korean-speaking female (47-year-old, high school graduate, assessed 9 months after diagnosis)	Bilateral medial temporal lobes and insula. Also, meningioma in the left cerebellum	Animal naming (Hachinski et al., 2006); letter fluency (/k/, /ng/, /s/)	10 items in action naming, 7 words in letter fluency. After a 6-week rehabilitation, 9 items action naming, 9 word in letter fluency
	Bacterial (treponema pallidum)	Ioannidis et al. (2014)	1 Greek-speaking male (52-year-old, assessed 6 months after first complaints, second assessment 6 months after first consultation)	Bilateral perisylvian cortical atrophy, more prominent in the left hemisphere. Theta-wave electroencephalographic activity in the left frontotemporal area	Object naming (5 animals, 5 objects; ACE-R, Konstantinopoulou et al., 2011)	Word-finding difficulties in the first assessment, resolved 6 months after
Encephalitis	Bacterial (tropheryma whippelii)	Benito-León et al. (2008)	1 Spanish-speaking male (63-year-old, assessed at hospital admission and 2 years after).	Mild bilateral frontotemporal atrophy. Single-photon emission computer tomography revealed decreased regional cerebral blood flow in frontal and temporal areas (greater decrease in left hemisphere)	Category fluency (animals, fruits)	Scores below the norm in category fluency (7 animals, 5 fruits). Within-normal scores 2 years after treatment.
	Bacterial (tropheryma whippelii)	Manzel et al. (2000)	1 English-speaking male (41-year-old, assessed 3–4 times for a 7-month period”)	Mesial temporal lobes and basal forebrain bilaterally, striatum, pallidum and hypothalamus. Thalamus relatively spared	Two comprehensive aphasia battery (Boston Diagnostic Aphasia Examination, BDAE; Goodglass & Kaplan, 1983; Multilingual Aphasia Examination, Benton et al., 1983), object naming (Boston naming test, BNT, Kaplan et al., 1983), letter fluency (“C”, “F”, “L”).	Letter fluency was below the norm, only in the first assessment. The other language tasks were within the norm
Encephalitis	Viral (SARS-CoV-2)	Almeria et al. (2020)	35 Spanish-speaking adults (24–60 years old, assessed 10–35 days from hospital discharge)	Not mentioned	Picture naming (Boston naming test, BNT), letter fluency (p), category fluency (animals) from Neuronorma project (Peña-Casanova et al., 2009).	Below normal scores depending on clinical complaints. People with headache showed below normal scores in letter fluency. People with loss of taste had below normal scores in picture naming. People who required oxygen therapy during hospitalization fared worse in category fluency.
Encephalitis	Viral (herpes simplex virus)	Baratelli et al. (2015)	1 Italian-speaking female (63-year-old, assessed one week, four weeks, and four months post onset)	Left insula and anterior parahippocampal region	Picture naming, naming on verbal definition, naming of famous faces, word-picture matching, verbal semantic questionnaire	Longer naming latencies in early assessments. Below-normal performance in all tasks with the exception of word-picture matching and verbal semantic questionnaire. No significant differences between biological entities and artifacts
	Viral (herpes simplex virus)	Barbarotto et al. (1996)	7 Italian-speaking adults (17–68 years old, assessed “few-months” to 4 years post-onset)	Temporal damage prevailing on the left in all but one participant who presented right temporal damage	Picture naming with biological categories: animals, fruits, vegetables; and artifacts: tools, furniture, vehicles. (Laiacona et al., 1993)	Four of seven participants were more impaired at naming biological categories. Frequency, familiarity, and name agreement influenced performance.
	Viral (herpes simplex virus)	E. De Renzi and Lucchelli (1994)	11 Italian-speaking adults (1 female with HSV, 49-year-old, assessed 4, 7, and 15 months after first hospital admission, and 10 age-matched controls)	Bilateral antero-medial temporal lobes, more marked on the left	Picture naming, naming to definition, picture identification (pointing to the correct item named, 8–10 possibilities); word-picture matching; naming by sound; describing perceptual differences; picture naming of objects/animals and non-objects/animals; recall the colour of an object/animal when reading its name; drawing objects/animals; sorting cards. Seven experiments with different lists of items/tests	Poor performance on animals and flowers, moderate on fruits, within normal range for objects
	Viral (herpes simplex virus)	Hanley et al. (1989)	24 English-speaking adults (1 male with HSV 60-year-old, assessed 15 years after first diagnosis and “some months” later, and two aged-matched control groups of 11 and 12 people)	Right superior temporal gyrus, anterior end of longitudinal fasciculus. Possible left temporal lobe damage	Picture naming; recognition of category members from definitions; recognizing famous faces and names (rate familiarity of the items, state person’s occupation, name the person); recognizing voices of famous people (Meudell et al., 1980); forced-choice tests with famous faces and names	More difficulty with biological entities than artifacts, with the exception of animals which is not different than artifacts. Difficulties with famous faces stable over a 4-month period (familiarity is rated low, few correct answers on occupations and name of the person). Poor at recognizing voices of famous people and forced-choice tests
	Viral (herpes simplex virus)	Lacidogna et al. (2020)	1 Italian-speaking female (26-year-old, assessed 16 months post-onset)	Marked left temporal and moderate bilateral orbital and mesial frontal, sparing inferior frontal gyrus (perfusion deficit)	Comprehensive aphasia battery (BADA, Miceli et al., 1994); picture naming (nouns, verbs, biological entities; artifacts); word-picture matching with auditory and written presentation (nouns, verbs; biological entities; artifacts)	More difficulty naming and comprehending nouns relative to verbs; no significant differences between biological entities and artifacts
	Viral (herpes simplex virus)	Tyler et al. (2002)	4 English-speaking adults (4 people with HSV, 35–68 years old, assessed 4–20 years post herpes onset)	Left temporal lobe (temporal and medial temporal cortex, temporal pole), two people had extensive right temporal damage	Past tense elicitation paradigm (i.e., two-sentence context, the second sentence needs to be completed – “My nose sometimes ‘bleeds’. Last night it … ”)	Poorer performance on irregular than regular past tense forms
	Viral (herpes simplex virus)	Warrington and Shallice (1984)	4 English-speaking adults (23–60 years old, assessed 1–8 months after first hospital admission)	Bilateral temporal lobes	Picture naming/ description; auditory naming/description. Seven experiments with different lists of items	More difficulty with biological entities than artifacts
Encephalitis	Parasitical (falciparum malaria)	Bangirana et al. (2016)	227 Luganda-speaking children (1.5–4 years old; 80 cerebral malaria, 86 severe malaria anaemia, 61 controls. Children with cerebral malaria and severe malaria anaemia, assessed 1 week after discharge or at enrolment, and then 6 and 12 months after)	Not specified	Interactive tasks of expressive and receptive language (Mullen Scales of early learning; Mullen, 1995). Testing performed in English and in Luganda when children did not understand English	Children with cerebral malaria and severe malaria anaemia were more impaired than children the control group. Children with cerebral malaria were more impaired than children with severe malaria anaemia
	Parasitical (falciparum malaria)	Carter et al. (2006)	487 Mijikenda-speaking children (6–9 years old; 152 cerebral malaria, 156 malaria and complicated seizures, 179 controls. Children were assessed 64–71 months in median after admission)	Not specified	Receptive grammar (Bishop, 1983); receptive vocabulary (Dunn & Dunn, 1981); syntax (Armstrong & Ainley, 1989); lexical-semantics (Crystal, 1992); pragmatics (Dewart & Summers, 1995); phonology and word finding (German, 1986). Mijikenda adaptations of standardized English tests	Children with cerebral malaria were more impaired than children with malaria and complicated seizures and the control group. Children with cerebral malaria were particularly impaired in receptive vocabulary and lexical semantics. Children with malaria and complicated seizures were particularly impaired in phonology and pragmatics
Encephalitis	Parasitical (taenia solium)	Otero et al. (1989)	1 Spanish-speaking male (7-year-old, informally assessed 8 and 4 months before admission, formally assessed on admission, and 6 months after treatment)	Left sylvian fissure	Informal testing: teacher and parental report; formal testing: intelligence scale (WISC, Wechsler Intelligence Scale for Children, version not mentioned)	Informal testing 8 months before treatment indicates poor story comprehension, telegraphic speech marked with phonological paraphasias (i.e., “llobeta” instead of “botella” [bottle], “manzan” instead of “manzana” [apple]) and other phonological or morphological omission errors (i.e., “él va casa” instead of “él va a la casa” [he goes home]; 4 months before treatment lack of response to oral commands and near mutism. Formal testing indicated a “mild delay in response and sentence formulation with decreased comprehension of spoken language” (verbal IQ = 89, performance IQ = 87). Improvement 6 months after treatment (no details are mentioned), but speech therapy was recommended.
	Parasitical (taenia solium)	Paradis and Goldblum (1989)	1 Gujarati-French-Malagasy-speaking male (25-year-old, assessed before surgery, two weeks, and 8 months after)	Right precentral gyrus	Comprehensive aphasia battery (Boiler & Hécaen, 1979); French-Guajarati and French-Malagasy versions of the Bilingual aphasia test (Paradis & Libben, 1987)	No problems with French across assessments. Difficulties with Guajarati only early after surgery (i.e., verbal fluency, word-finding difficulties, and borrowing French words in spontaneous speech). Difficulties with Malagasy only 8 months after surgery (i.e., syntactic comprehension, verbal fluency, word-finding difficulties)
Meningo- Encephalitis	Bacterial (mycobacterium tuberculosis)	Booth and Curtis (1893)	1 English-speaking male (24-year-old, assessed before and after surgery)	Left frontal lobe	Spontaneous speech	Mild word-finding difficulties, intact auditory comprehension. No difficulties after surgery
	Bacterial (mycobacterium tuberculosis)	Garcia-Grimshaw et al. (2018)	1 Spanish-speaking female (24-year-old, assessed upon hospital admission)	Left parietal lobe, cerebellum, and arcuate fasciculus	Naming, following simple commands, reading out loud, writing, repetition of simple sentences (the tests are not specified)	Problems with repetition and some paraphasias (type unspecified) in spontaneous speech.
	Bacterial (mycobacterium tuberculosis)	Hinsdale (1901)	1 English-speaking male (35-year-old, assessed 2 years after second pneumonia – first pneumonia 14 years before, and re-assessed 1 year after)	Left inferior parietal lobe	Spontaneous speech, naming real objects (i.e., pencil, coin), reading the alphabet, word reading (nouns).	More difficulties in the first assessment than one year after. Difficulties with lexical retrieval upon naming real objects (not semantics, as responded correctly to semantic-related questions, e.g., for a pencil, is this a knife? is this something to write with?); difficulties reading the alphabet, and reading words (semantic and phonological paraphasias)
Meningo-encephalitis	Bacterial (borrelia burgdoferi)	Benke et al. (1995)	40 German-speaking adults (20 people with Lyme disease; 35–72 years; assessed ~4 years on average after infection [4–100 months]; 20 age-matched controls)	Facial neve palsy (4 people), multiple cranial nerve involvement (1 person), left-sided weakness (1 person), minor nonspecific abnormalities (14 people)	Letter fluency (1 task, letter “s”); rapid syllable repetition (Mateer & Kimura, 1977)	Both tasks are significantly impaired, relatively to aged-matched control
	Bacterial (borrelia burdoferi)	Krupp et al. (1991)	25 English-speaking adults (15 people with Lyme disease; 30–40 years; assessed ~7 months after infection; 10 age-matched controls)	8/15 people with Lyme disease did MRI. 6 had normal scans. 2 people presented “one or more small areas” of white matter abnormalities.	Letter fluency (“C”, “F”, “L”)	Letter fluency significantly impaired, relatively to age-matched controls
	Bacterial (borrelia burgdoferi)	Sokolov et al. (2015)	1 Swiss German-speaking female (16-year-old, assessed 3 and 24 hours after symptom onset)	Left parietotemporal junction (perfusion deficit, no structural brain damage or vasculitis as seen with MRI)	Spontaneous speech, repetition	Reduced speech production and comprehension, phonological paraphasias preserved repetition. Symptoms resolved 24 hours after antibacterial and antiviral treatment.
	Bacterial (borrelia burgdoferi)	Svetina et al. (1999)	44 English-speaking adults (30–40 years-old; time of assessment after infection not mentioned, but 91% where in a chronic stage; 43 age-matched controls)	Not mentioned	Object naming (BNT, Kaplan et al., 1983), letter fluency (“C”, “F”, “L”), category fluency (“animals”, “fruits”, “vegetables”); subjective reports	55% of people with Lyme disease (vs 14% of people in the control group) reported subjective word-finding difficulties; people with Lyme disease were more impaired in object naming; no differences in the total number of words in fluency tasks.
Meningo-encephalitis	Viral (HIV)	Abusamra et al. (2016)	20 Spanish-speaking adults (26–57 years-old, assessment time not mentioned)	Not mentioned	Comprehension and repetition of conversational and narrative prosody, interpretation of metaphors and indirect speech tasks, fluency tasks (letter and semantic), semantic judgment (Ferreres et al., 2007)	Measures of narrative discourse, fluency (verbal and semantic) and metaphor comprehension were the most impaired.
	Viral (HIV)	Becker et al. (1997)	267 English-speaking adults (200 people with HIV, and 67 people without HIV, 20–40 years-old, assessment time not mentioned)	Not mentioned	Category fluency (i.e., animals) and letter fluency (i.e., “F”, “A”, “S”)	People with HIV without dementia fared lower on category fluency and letter fluency relative to a control sample
	Viral (HIV)	Kambanaros et al. (2019)	80 Greek-speaking adults (40 people with HIV, and 40 people without HIV, 19–59 years old, assessment time?	Not mentioned	Sentence repetition (8 different structures), category fluency (i.e., objects, animals, fruits); letter fluency (i.e., X, A, Σ)	People with HIV fared lower on sentence repetition, category and letter fluency relative to a control sample
	Viral (HIV)	P. McCabe et al. (2002)	5 English-speaking adults (34–67 years-old, assessment time not mentioned).	Not mentioned	Comprehensive language test (Western Aphasia Battery, Kertesz, 1982), Shortened Token Test (De Renzi & Faglioni, 1978), Right hemisphere language battery (Bryan, 1995), Communicative Effectiveness Index (Lomas et al., 1989), Pragmatic Protocol (Prutting & Kittchner, 1987), object naming (BNT, Kaplan et al., 1983), spontaneous speech (i.e., Cinderella story, event recount), category and letter fluency	Normal scores on comprehensive language testing in spite of word finding difficulties in spontaneous speech, object naming, spelling, reduced word fluency, and disturbances in pragmatic skills (i.e., metaphor interpretation)
	Viral (HIV)	P. J. McCabe et al. (2008)	3 English-speaking males (36-year-old with AIDS and dementia; 34-year-old with AIDS and no dementia; 34-year old healthy control; assessed a first time, 6 months and 13 months after)	Not mentioned	Comprehensive language test (Western Aphasia Battery, Kertesz, 1982), Shortened Token Test (De Renzi & Faglioni, 1978), Right hemisphere language battery (Bryan, 1995), Communicative Effectiveness Index (Lomas et al., 1989), Pragmatic Protocol (Prutting & Kittchner, 1987), object naming (BNT, Kaplan et al., 1983), spontaneous speech (i.e., Cinderella story, event recount), category (i.e., animals) and letter fluency (i.e., /s/)	The person with AIDS and dementia had a pragmatic language disorder which was particularly marked during spontaneous speech (e.g., self-focused, verbose, unable to maintain topic). Also, he had some word finding difficulties, circumlocutions but largely. Slight differences across assessment times, attributed to non-linguistic factors such as attention or fatigue
	Viral (HIV)	Millikin et al. (2004)	217 English-speaking adults with HIV (28 people characterized as asymptomatic; 58 mildly symptomatic; 131 met criteria for AIDS; 30–50 years-old, assessment time not mentioned).	Not mentioned	Letter fluency (“F”, “A”, “S”) and category fluency (i.e., animals).	Relative to a normative sample and to people with no to mild symptoms, people with severe symptoms fared worse in letter fluency but not in category fluency. Furthermore, people with severe symptoms produced fewer switches.
	Viral (HIV)	Sheppard et al. (2017)	128 English-speaking adults (50–56 years-old, 40 with HIV, 48 HIV-seronegative controls matched for age, and 40 HIV seronegative controls aged ≥65)	Not mentioned	Object naming (BNT, Goodglass et al., 2001)	No differences between groups in object naming.
	Viral (HIV)	White et al. (1997)	39 English-speaking adults (30–50 years-old, 9 with HIV and dementia, 15 HIV-seropositive without dementia, 15 HIV-seronegative controls)	Not mentioned	Letter fluency (F, A, S; Benton et al., 1983); category fluency (animals, fruits, vegetables; Monsch et al., 1992); object naming (BNT, Kaplan et al., 1983)	People with HIV and dementia scored lower than the other two groups in letter fluency. No differences between groups in object naming or category fluency
	Viral (HIV)	Woods et al. (2004)	102 English-speaking adults (25–50 years-old, 21 with HIV and dementia, 51 with HIV, 30 healthy controls, assessment time not mentioned)	Not mentioned	Letter fluency (F, A, S; Benton et al., 1983)	People with HIV and dementia produced fewer correct words, switches, and more errors than people with HIV without dementia and healthy controls. No differences in cluster size were attested
Meningo-encephalitis	Viral (enterovirus)	Kim et al. (2012)	1 Korean-speaking female (23-year-old, assessed 4 days after hospital admission)	Left frontal lobe	Comprehension of complex sentences, word repetition and object naming	Impaired scores 4 days after hospital admission, no impairments 3 month after pharmaceutical treatment
Meningo-encephalitis	Fungal (aspergillus fumigatus)	Lin et al. (2014)	1 English-speaking male (32-years-old, assessed 55, 57, 68 days after hospital admission)	Left middle cerebral artery territory	Reading, conversation, repetition	Severe language problems early after infract due to air emboli, resolving over time with presence of paraphasias (type unspecified) and repetition, no comprehension difficulties.

*ACE-R = Addenbrooke’s Cognitive Examination‐Revised (Konstantinopoulou et al., 2011); AIDS = Acquired immune deficiency syndrome; BADA = Battery for Analysis of Aphasic Deficits (Miceli et al., 1994); BNT = Boston naming test (Kaplan et al., 1983); CELF-3 = Clinical evaluation of language fundamentals – 3rd edition (Semel et al., 1995); DART = Dutch Adult Reading Test (Schmand & Lindeboom, 1992); HSV = Herpes simples virus; MWT-B – Multiple choice vocabulary test (Lehrl, 1995); NA = Not applicable; SI = Streptococcus intermedius; HIV = Human immunodeficiency virus; TLC-E = Test for language competence – expanded edition (Wiig & Secord, 1989); WAIS = Wechsler Adult Intelligence Scale (Dahl, 1986).

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