Klüver-Bucy Syndrome Following Traumatic Brain Injury: A Systematic Synthesis and Review of Pharmacological Treatment From Cases in Adolescents and Adults
Abstract
Methods
Inclusion and Exclusion Criteria
Search Strategy
Study Selection
![](/cms/10.1176/appi.neuropsych.18050112/asset/images/large/appi.neuropsych.18050112f1.jpeg)
Assessment of Methodological Quality
Data Extraction
Results
Study Selection
Data Synthesis
Demographic Characteristics
Study | Case | Age at Injury (Years) | Sex | Country | Mechanism of injury | Loss of Consciousness | Glasgow Coma Scale (GCS) Scorea | Brain MRI and Computerized Tomography Results |
---|---|---|---|---|---|---|---|---|
Aygun et al.24 | 29 | Male | Turkey | Road traffic accident | No | 14 | Contusions of bilateral temporal lobes | |
Bhat et al.22 | 30 | Male | India | Road traffic accident | Not reported | Not reported | Mild right anterior temporal gyrus atrophy | |
Caro and Jimenez7 | Late 20s | Male | United States | Sport | No | Increased size of frontal lobes; right parietal white matter lesions; infratentorial lesions in cerebellar hemispheres | ||
Deginal and Changty23 | 16 | Male | India | Road traffic accident | Yes | 10 | Bilateral temporal contusions with edema | |
Fiume and Fiume Garelli26 | 23 | Male | Italy | Road traffic accident | Comab | Imaging not conducted; craniotomy subtemporal | ||
Góscínski et al.19,20 | 1 | 23 | Male | Poland | Road traffic accident | Yes | 4 | Left subdural hematoma |
Right-sided cerebral edema | ||||||||
Góscínski et al.19,20 | 2 | 67 | Male | Poland | Fall | Yes | 7 | Intracerebral bitemporal hematoma |
Hardy and Aldridge2 | 16 | Male | United States | Firearm | No | Right temporal lobe lesion | ||
Hooshmand et al.34 | 16 | Female | United States | Road traffic accident | Yes, coma | Right temporal lobe damage | ||
Isern31 | 37 | Female | United States | Firearm | No | Bitemporal lobe damage | ||
Kwiatwoski et al.27 | 1 | 16 | Male | Poland | Road traffic accident | Yes | 3 | Bilateral contusions: temporal and parietal lobes |
Hemorrhage into subcortical nuclei; paracerebral hematoma | ||||||||
Kwiatwoski et al.27 | 2 | 16 | Female | Poland | Road traffic accident | Yes, GCS score=3 | Left temporal subdural hematoma | |
Right hemisphere hemorrhagic contusion and cerebral edema | ||||||||
Lilly et al.6 | 57 | Male | United States | Road traffic accident | Yes | Bilateral damage to inferior temporal lobes | ||
Morcos and Guirgis32 | 39 | Male | United States | Fall | Yes | Inferior left temporal damage | ||
Moviat et al.28 | 1 | 13 | Female | Netherlands | Road traffic accident | <7 | Left-sided parietal subdural hematoma; generalized edema | |
Loss of basal cisterns; left temporal plus right frontotemporal contusions | ||||||||
Moviat et al.28 | 2 | 13 | Female | Netherlands | Road traffic accident | 7 | Left-sided parietal subdural hematoma; generalized edema | |
Loss of basal cisterns; bilateral frontotemporal contusion | ||||||||
Moviat et al.28 | 5 | 14 | Male | Netherlands | Road traffic accident | GCS score=7 | Right frontotemporal hematoma; right frontal atrophia | |
Hypodensity in left thalamus | ||||||||
Salim et al.48 | 24 | Female | United States | Road traffic accident | No | 14 | Focal axonal injury to left temporal lobe | |
Slaughter et al.29 | 1 | Late 20s | Male | United States | Road traffic accident | Yes | 3Tc | Left intraparenchymal hematoma; subarachnoid hemorrhage |
Left temporal lobe contusions; bilateral enlargement–temporal horns | ||||||||
Slaughter et al.29 | 2 | Early 20s | Male | United States | Road traffic accident | Yes | 6 | Bilateral small frontal lobe contusions |
Smigielski and Boeve36 | 25 | Female | United States | Road traffic accident | Not reported | Not reported | Bilateral temporal lobe contusions; left-sided frontal injury | |
Stewart35 | 20 | Male | United States | Road traffic accident | Not reported | Not reported | Bilateral frontal and temporal encephalomalacia | |
Yoneoka et al.25 | 17 | M | Japan | Sport | Yes, coma | Right-sided acute subdural hematoma with transtentorial herniation | ||
York and McCarter30 | 25 | Male | United States | Firearm | 5Tc | Bifrontal and temporal lobe contusions |
Injury Severity
Brain Imaging
KBS Symptoms
Study | Case | Time at KBS Onsetb | Memory | Visual Agnosia | Placidity | Change in Diet | Hyperoral | Sexual Hyperactivity | Hypermetamorphoses | Behavior | Full or Partial KBS |
---|---|---|---|---|---|---|---|---|---|---|---|
Aygunet al.24 | T1 | Not described | + | + | + | + | + | Not described | FA | Full | |
Bhat et al.22 | T3 | Not described | + | + | Not described | + | + | + | FA | Partial | |
Caro and Jimenez7 | T5 | Not described | Not described | + | + | + | + | Not described | A | Partial | |
Deginal and Changty23 | T2 | Not described | + | + | + | + | + | + | A | Full | |
Fiume and Fiume Garelli26 | T1 | + | Not described | + | + | + | + | + | D | Partial | |
Góscínski et al.19,20 | 1 | T2 | + | Not described | Not described | + | + | + | Not described | A/FA | Partial |
Góscínski et al.19,20 | 2 | T2 | Not described | Not described | Not described | + | + | + | + | A | Partial |
Hardy and Aldridge2 | T1 | + | + | + | + | Not described | + | + | FA | Partial | |
Hooshmand et al.34 | T3 | + | Not described | Not described | + | + | + | Not described | A | Partial | |
Isern31 | T1 | + | + | + | + | + | + | + | A | Full | |
Kwiatwoski et al.27 | 1 | T1 | Not described | + | + | + | + | + | Not described | A | Partial |
Kwiatwoski et al.27 | 2 | T1 | + | Not described | Not described | + | + | + | + | A/D | Partial |
Lilly et al.6 | T2 | + | + | + | + | + | + | + | FA/R | Full | |
Morcos and Guirgis32 | T1 | + | Not described | Not described | + | Not described | + | + | A | Partial | |
Moviat et al.28 | 1 | T4 | + | Not described | + | + | Not described | + | + | RE | Partial |
Moviat et al.28 | 2 | T3 | + | Not described | + | Not described | Not described | + | + | RE | Partial |
Moviat et al.28 | 5 | T1 | + | Not described | + | + | + | + | Not described | RE | Partial |
Salim et al.48 | T1 | + | Not described | + | + | Not described | + | Not described | A | Partial | |
Slaughter et al.29 | 1 | T2 | + | Not described | Not described | + | + | + | Not described | A/R | Partial |
Slaughter et al.29 | 2 | T1 | + | Not described | Not described | Not described | + | N | Not described | A/FA/R | Partial |
Smigelski and Boeve36 | T5 | Not described | Not described | Not described | Not described | + | + | Not described | A | Partial | |
Stewart35 | T1 | + | Not described | + | + | Not described | + | + | A | Partial | |
Yoneoka25 | T2 | Not described | + | + | + | + | + | + | N/R | Full | |
York and McCarter30 | T1 | + | Not described | Not described | + | Not described | + | Not described | N/R | Partial |
Recovery Over Time: All Case Subjects (N=24)
Study | Case | KBS Symptom Improvement | Duration of KBS | Treatment Response and Outcome |
---|---|---|---|---|
Aygun et al.24 | Positive | 5 days | Complete improvement | |
Bhat et al.22 | Positive | 3 weeks | Asymptomatic | |
Caro and Jimenez7 | Partial | Gradual improvement in behavior and cognition | ||
Deginal et al.23 | Partial | 30% Improvement in behavior and KBS symptoms when measured at 8 weeks post-TBI | ||
Fiume and Fiume Garelli26 | No improvement | Died | Progressive deterioration leading to death | |
Góscínski et al.19,20 | 1 | No improvement | Ongoing | Reduced intellectual capacity and functioning (7 years) |
Irritable, verbally aggressive, poor memory, apathy, and no libido (25 years) | ||||
Góscínski et al.19,20 | 2 | No improvement | Ongoing | Prolonged psychiatric disorders, social maladaptation, aggression, and self-harming |
Hardy and Aldridge2 | Partial | 15 days | Improved appetite, language, and no sexual comments 15 days post-TBI | |
Obsessive-compulsive disorder and blunt affect persisted | ||||
Hooshmand et al.34 | Positive | 1 year | Seizures ended in 24 hours; hyperorality disappeared; concentration improved; substantial improvement in memory | |
Isern31 | Not reported | 4–5 months | ||
Kwiatwoski et al.27 | 1 | Positive | Managed to effectively return to preaccident functioning, including work | |
Kwiatwoski et al.27 | 2 | Partial | Persisted symptoms of hyperorality 4 years post-TBI | |
Improvement in dietary habits, emotional dullness, emotionality, physical violence, and anger management | ||||
Lilly et al.6 | Positive | 1 month | ||
Morcos and Guirgis32 | Not reported | |||
Moviat et al.28 | 1 | No improvement | No change after 6 years rehabilitation | |
Moviat et al.28 | 2 | No improvement | No change after 3 years rehabilitation | |
Moviat et al.28 | 5 | Partial | 2 years | Bilateral pyramidal signs improved |
No change after 3 years rehabilitation | ||||
Salim et al.48 | Positive | Approximately 7 days | Resolved | |
Slaughter29 | 1 | Positive | 3.5 months | Complete resolution |
Slaughter et al.29 | 2 | Positive | 18 days | Reduced symptoms of agitation/lip chewing; symptoms did not recur |
Smigelski and Boeve36 | Positive | 8 months | Impressive neurobehavioral and neurocognitive recovery | |
Stewart35 | Positive | <3 months | Positive improvement (gradual decrease, ceased violent attacks) | |
Yoneoka et al.25 | Positive | 14 months | Transient symptoms of KBS; returned to high school and then college | |
York and McCarter30 | Partial | Improvement in residual memory and cognition |
Pharmacological Treatment
Study | Case | Pharmacotherapy |
---|---|---|
Bhat et al.22 | Carbamazepine; no further details provided | |
Caro and Jimenez7 | Valproate changed to topiramate, quetiapine, propranolol, benztropine, and haloperidol | |
Deginal and Changty23 | Carbamazepine (200 mg b.i.d.) | |
Góscínski et al.19,20 | 1 | Carbamazepine |
Góscínski et al.19,20 | 2 | Carbamazepine (400 mg b.i.d.) |
Hooshmand et al.34 | Chlorpromazine (300 mg/day) (discontinued) | |
Carbamazepine (1,000 mg/day) (commenced after chlorpromazine) | ||
Kwiatwoski et al.27 | 1 | Haloperidol |
Carbamazepine administered orally three times per day (200 mg/per day); serum level 6 μg/ml | ||
Kwiatwoski et al.27 | 2 | Carbamazepine administered orally three times per day (200 mg/day); 6 μg/ml serum level |
Morcos and Guirgis32 | Carbamazepine (400 mg b.i.d.) | |
Slaughter et al.29 | 1 | Carbamazepine (600 mg/day); propranolol (no change in baseline behavior) |
Trazodone | ||
Sertraline (titrated to 150 mg); substituted with fluoxetine (40 mg in the morning and 20 mg at noon) | ||
Slaughter et al.29 | 2 | Haloperidol; substituted with olanzapine |
Lorazepam, valproic acid, thiothixene, and bromocriptine | ||
Sertraline (150 mg/per day) | ||
Stewart 35 | Carbamazepine; serum level 9–11 μg/ml for 3 weeks, then 8–9 ug/ml for 1 year |
Treatment With Carbamazepine
Response to Pharmacological Treatment (12 Cases)
Methodological Quality
Study | Case | Q1 | Q2 | Q3 | Q4 | Q5 | Q6 | Q7 | Q8 |
---|---|---|---|---|---|---|---|---|---|
Aygun et al.24 | Y | Y | Y | Y | Y | N/A | N | Y | |
Bhat et al.t22 | Y | Y | Y | Y | Y | Y | N | Y | |
Caro and Jimenez7 | Y | Y | Y | Y | Y | Y | Y | Y | |
Deginal and Changty23 | Y | Y | Y | Y | Y | Y | N | Y | |
Fiume and Fiume Garelli26 | Y | N | Y | Y | N | N | N | N | |
Góscínski et al.19,20 | 1 | Y | N | Y | Y | N | N | N | Y |
Góscínski et al.19,20 | 2 | Y | N | Y | Y | N | N | N | Y |
Hardy and Aldridge2 | Y | N | Y | Y | N | Y | N | N | |
Hooshmand et al.34 | Y | Y | Y | Y | Y | Y | Y | Y | |
Isern31 | Y | Y | Y | Y | Y | Unclear | N | N | |
Kwiatwoski et al.27 | 1 | Y | Y | Y | Y | Y | Y | N | Y |
Kwiatwoski et al.27 | 2 | Y | Y | Y | Y | Y | Y | N | Y |
Lilly et al.6 | Y | N | Y | Y | Y | Y | N | Y | |
Morcos and Guirgis32 | Y | Y | Y | Y | Y | Y | N | Y | |
Moviat et al.28 | 1 | Y | N | Y | Y | N | N | Y | Y |
Moviat et al.28 | 2 | Y | N | Y | Y | N | N | Y | Y |
Moviat et al.28 | 5 | Y | N | Y | Y | N | N | Y | Y |
Salim et al.48 | Y | N | Y | Y | N/A | N | N | Y | |
Slaughter et al.29 | 1 | Y | Y | Y | Y | Y | Y | Y | Y |
Slaughter et al.29 | 2 | Y | N | Y | Y | Y | Y | Y | Y |
Smigelski and Boeve36 | Y | N | Y | Y | N | Y | N | N | |
Stewart35 | Y | Y | Y | Y | Y | Y | N | Y | |
Yoneoka et al.25 | Y | Y | Y | Y | Y | Y | N | Y | |
York and McCarter30 | Y | Y | Y | Y | N | N | N | Y |
Discussion
Conclusions
Acknowledgments
Supplementary Material
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