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April 13, 2021; 96 (15) Article

Temporal Cognitive and Brain Changes in Korsakoff Syndrome

Angéline Maillard, Alice Laniepce, Nicolas Cabé, Céline Boudehent, Gael Chételat, Laurent Urso, Francis Eustache, François Vabret, View ORCID ProfileShailendra Segobin, View ORCID ProfileAnne-Lise Pitel
First published February 26, 2021, DOI: https://doi.org/10.1212/WNL.0000000000011749
Angéline Maillard
From Normandie Université (A.M., A.L., N.C., C.B., F.E., F.V., S.S., A.-L.P.), UNICAEN, PSL Université Paris, EPHE, INSERM, U1077, CHU de Caen, GIP Cyceron, Neuropsychologie et Imagerie de la Mémoire Humaine; Service d'addictologie (N.C., C.B., F.V.), Centre Hospitalier Universitaire de Caen; Normandie Université (G.C.), UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” Institut Blood and Brain at Caen-Normandie, Cyceron, Caen; Service d'addictologie (L.U.), Centre Hospitalier de Roubaix; and Institut Universitaire de France (A.-L.P.), Paris.
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Alice Laniepce
From Normandie Université (A.M., A.L., N.C., C.B., F.E., F.V., S.S., A.-L.P.), UNICAEN, PSL Université Paris, EPHE, INSERM, U1077, CHU de Caen, GIP Cyceron, Neuropsychologie et Imagerie de la Mémoire Humaine; Service d'addictologie (N.C., C.B., F.V.), Centre Hospitalier Universitaire de Caen; Normandie Université (G.C.), UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” Institut Blood and Brain at Caen-Normandie, Cyceron, Caen; Service d'addictologie (L.U.), Centre Hospitalier de Roubaix; and Institut Universitaire de France (A.-L.P.), Paris.
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Nicolas Cabé
From Normandie Université (A.M., A.L., N.C., C.B., F.E., F.V., S.S., A.-L.P.), UNICAEN, PSL Université Paris, EPHE, INSERM, U1077, CHU de Caen, GIP Cyceron, Neuropsychologie et Imagerie de la Mémoire Humaine; Service d'addictologie (N.C., C.B., F.V.), Centre Hospitalier Universitaire de Caen; Normandie Université (G.C.), UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” Institut Blood and Brain at Caen-Normandie, Cyceron, Caen; Service d'addictologie (L.U.), Centre Hospitalier de Roubaix; and Institut Universitaire de France (A.-L.P.), Paris.
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Céline Boudehent
From Normandie Université (A.M., A.L., N.C., C.B., F.E., F.V., S.S., A.-L.P.), UNICAEN, PSL Université Paris, EPHE, INSERM, U1077, CHU de Caen, GIP Cyceron, Neuropsychologie et Imagerie de la Mémoire Humaine; Service d'addictologie (N.C., C.B., F.V.), Centre Hospitalier Universitaire de Caen; Normandie Université (G.C.), UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” Institut Blood and Brain at Caen-Normandie, Cyceron, Caen; Service d'addictologie (L.U.), Centre Hospitalier de Roubaix; and Institut Universitaire de France (A.-L.P.), Paris.
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Gael Chételat
From Normandie Université (A.M., A.L., N.C., C.B., F.E., F.V., S.S., A.-L.P.), UNICAEN, PSL Université Paris, EPHE, INSERM, U1077, CHU de Caen, GIP Cyceron, Neuropsychologie et Imagerie de la Mémoire Humaine; Service d'addictologie (N.C., C.B., F.V.), Centre Hospitalier Universitaire de Caen; Normandie Université (G.C.), UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” Institut Blood and Brain at Caen-Normandie, Cyceron, Caen; Service d'addictologie (L.U.), Centre Hospitalier de Roubaix; and Institut Universitaire de France (A.-L.P.), Paris.
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Laurent Urso
From Normandie Université (A.M., A.L., N.C., C.B., F.E., F.V., S.S., A.-L.P.), UNICAEN, PSL Université Paris, EPHE, INSERM, U1077, CHU de Caen, GIP Cyceron, Neuropsychologie et Imagerie de la Mémoire Humaine; Service d'addictologie (N.C., C.B., F.V.), Centre Hospitalier Universitaire de Caen; Normandie Université (G.C.), UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” Institut Blood and Brain at Caen-Normandie, Cyceron, Caen; Service d'addictologie (L.U.), Centre Hospitalier de Roubaix; and Institut Universitaire de France (A.-L.P.), Paris.
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Francis Eustache
From Normandie Université (A.M., A.L., N.C., C.B., F.E., F.V., S.S., A.-L.P.), UNICAEN, PSL Université Paris, EPHE, INSERM, U1077, CHU de Caen, GIP Cyceron, Neuropsychologie et Imagerie de la Mémoire Humaine; Service d'addictologie (N.C., C.B., F.V.), Centre Hospitalier Universitaire de Caen; Normandie Université (G.C.), UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” Institut Blood and Brain at Caen-Normandie, Cyceron, Caen; Service d'addictologie (L.U.), Centre Hospitalier de Roubaix; and Institut Universitaire de France (A.-L.P.), Paris.
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François Vabret
From Normandie Université (A.M., A.L., N.C., C.B., F.E., F.V., S.S., A.-L.P.), UNICAEN, PSL Université Paris, EPHE, INSERM, U1077, CHU de Caen, GIP Cyceron, Neuropsychologie et Imagerie de la Mémoire Humaine; Service d'addictologie (N.C., C.B., F.V.), Centre Hospitalier Universitaire de Caen; Normandie Université (G.C.), UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” Institut Blood and Brain at Caen-Normandie, Cyceron, Caen; Service d'addictologie (L.U.), Centre Hospitalier de Roubaix; and Institut Universitaire de France (A.-L.P.), Paris.
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Shailendra Segobin
From Normandie Université (A.M., A.L., N.C., C.B., F.E., F.V., S.S., A.-L.P.), UNICAEN, PSL Université Paris, EPHE, INSERM, U1077, CHU de Caen, GIP Cyceron, Neuropsychologie et Imagerie de la Mémoire Humaine; Service d'addictologie (N.C., C.B., F.V.), Centre Hospitalier Universitaire de Caen; Normandie Université (G.C.), UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” Institut Blood and Brain at Caen-Normandie, Cyceron, Caen; Service d'addictologie (L.U.), Centre Hospitalier de Roubaix; and Institut Universitaire de France (A.-L.P.), Paris.
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Anne-Lise Pitel
From Normandie Université (A.M., A.L., N.C., C.B., F.E., F.V., S.S., A.-L.P.), UNICAEN, PSL Université Paris, EPHE, INSERM, U1077, CHU de Caen, GIP Cyceron, Neuropsychologie et Imagerie de la Mémoire Humaine; Service d'addictologie (N.C., C.B., F.V.), Centre Hospitalier Universitaire de Caen; Normandie Université (G.C.), UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders,” Institut Blood and Brain at Caen-Normandie, Cyceron, Caen; Service d'addictologie (L.U.), Centre Hospitalier de Roubaix; and Institut Universitaire de France (A.-L.P.), Paris.
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Temporal Cognitive and Brain Changes in Korsakoff Syndrome
Angéline Maillard, Alice Laniepce, Nicolas Cabé, Céline Boudehent, Gael Chételat, Laurent Urso, Francis Eustache, François Vabret, Shailendra Segobin, Anne-Lise Pitel
Neurology Apr 2021, 96 (15) e1987-e1998; DOI: 10.1212/WNL.0000000000011749

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Abstract

Objective To investigate cognitive and brain changes in patients with Korsakoff syndrome (KS) over months and up to 10 years after the diagnosis.

Methods Two groups of 8 patients with KS underwent neuropsychological, motor, and neuroimaging investigations, including structural MRI and 18F-fluorodeoxyglucose-PET. The KSC group, recruited at Caen University Hospital, was examined early after the KS diagnosis (KSC-T1) and 1 year later (KSC-T2). The KSR group, recruited at nursing home at Roubaix, was evaluated 10 years after the diagnosis. Longitudinal comparisons in KSC explored short-term changes, while cross-sectional comparisons between KSC-T1 and KSR informed about long-term changes.

Results No cognitive, motor, or brain deterioration occurred over time in patients with KS. There was no clear improvement either, with only modest recovery in the frontocerebellar circuit. Compared to the norms, KSC-T1 had severe episodic memory impairments, ataxia, and some executive dysfunctions. They also presented widespread atrophy and hypometabolism as well as cerebellar hypermetabolism compared to 44 healthy matched controls. Episodic memory remained significantly impaired in KSC-T2 and KSR. Contrary to KSC at T1 and T2, KSR had preserved inhibition abilities. Atrophy was similar but less extended in KSC-T2 and even more limited in KSR. At all times, the thalamus, hypothalamus, and fornix remained severely atrophied. Hypometabolism was still widespread in KSC-T2 and KSR, notably affecting the diencephalon. Cerebellar metabolism decreased over time and normalized in KSR, whereas motor dysfunction persisted.

Conclusion In KS, structural and metabolic alterations of the Papez circuit persisted over time, in accordance with the irreversible nature of amnesia. There was neither significant recovery as observed in patients with alcohol use disorder nor progressive decline as in neurodegenerative diseases.

Glossary

AUD=
alcohol use disorder;
CVLT=
California Verbal Learning Test;
DSM-5=
Diagnostic and Statistical Manual of Mental Disorders, 5th edition;
FCC=
frontocerebellar circuit;
FCSRT=
Free and Cued Selective Reminding Test;
FDG=
18F-fluorodeoxyglucose;
FWE=
family-wise error;
HC=
healthy controls;
IMAP=
Imagerie Multimodale de la Maladie d’Alzheimer à un stade Précoce;
KS=
Korsakoff syndrome;
KSC=
patients with KS recruited at Caen University Hospital;
KSR=
patients with KS recruited in a nursing home at Roubaix;
MNI=
Montreal Neurologic Institute;
PC=
Papez circuit

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • ↵* These authors contributed equally to this work.

  • Received August 6, 2020.
  • Accepted in final form January 13, 2021.
  • © 2021 American Academy of Neurology
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