NIRVE ROUNDS

Main Case

#NeverForget
 Chief Complain

Memory loss

3
 CASE

○ 36/Female G3P2
○ Right-handed
○ Medical Representative
○ College graduate
○ Married with 2 children

4
 HISTORY OF PRESENT ILLNESS

12 months
❖ While going to the bathroom she complained of diplopia that rapidly
progressed to loss of vision on both eyes.
❖ Rapid deterioration of sensorium from awake to stuporous within 1 day.
❖ No complains of behavioral change, headache, seizure, other focal deficit,
incontinence, dyspnea.

5
 HISTORY OF PRESENT ILLNESS

Admitted at Local Hospital

❖Underwent Cranial MRI with contrast

6
 HISTORY OF PRESENT ILLNESS

11 months
❖ Given unrecalled IV medications for 10 days.
❖ Improvement in sensorium to awake, with regard, follows simple
commands.
❖ Deficits:
❖Anterograde and retrograde amnesia
❖Bilateral horizontal gaze-evoked nystagmus
❖Dysphagia
❖Dysarthria
❖Upper extremity rigidity
❖Lower extremity dystaxia
7
 HISTORY OF PRESENT ILLNESS

9 months
❖ Discharged: Wheel-Chair bound
❖Anterograde and retrograde amnesia
❖Bilateral horizontal gaze-evoked nystagmus
❖Dysphagia
❖Dysarthria
❖Upper extremity rigidity
❖Lower extremity dystaxia

8
 HISTORY OF PRESENT ILLNESS

7 months
❖ Re-admitted for Cesarean Section
❖ Repeat imaging done
❖ Still with persistent but non-progressive deficits
❖Anterograde and retrograde amnesia
❖Bilateral horizontal gaze-evoked nystagmus
❖Dysphagia
❖Dysarthria
❖Upper extremity rigidity
❖Lower extremity dystaxia
9
 QUESTION
What is the most common etiology are you considering at this point?

❖Vascular
❖Infectious
❖Autoimmune
❖Toxic / Metabolic
❖Neoplastic
❖Degenerative
10
12 months
PTA

11
12 months
PTA

12
7 months PTA

13
3 months

14
12 months PTA 7 months PTA
 HISTORY OF PRESENT ILLNESS

3 months
❖ Re-admitted to another institution for further work-up.

15
 QUESTION
What additional studies would you want to perform?

❖CSF Studies
❖21 Channel EEG
❖Repeat Imaging
❖Serum Anti-AQP4
❖Anti-MOG
❖AE antibody testing
❖Toxicology Screening
16
 HISTORY OF PRESENT ILLNESS

3 months
❖Lumbar Tap:
CSF Study:
❖ Colorless, clear
❖ RBC: 331, WBC 1 (100% Lymphocyte)
❖ Total Protein: 27.20, Glucose 66.9%
❖21 channel EEG:
❖ Diffuse low voltage 5-7 Hz theta activity with posterior dominance, poor
reactivity and absent epileptiform discharge.
❖Serum Anti-NMDA R Antibody: negative

17
18
19
 HISTORY OF PRESENT ILLNESS

3 months
❖ Started on Methylprednisolone Pulse Therapy for 4 days without
improvement
❖ Started on Olanzapine, Baclofen and Piracetam
❖ Still no improvement

20
 HISTORY OF PRESENT ILLNESS

❖ Re-admitted to our institution for further work-up.

21
 REVIEW OF SYSTEMS

❖ General
❖ (+) Weight loss, no febrile episodes, no easy fatiguability
❖ HEENT
❖ No Trauma, no bleeding, rest unremarkable
❖ Cardiorespiratory
❖ No chest pain, HF S/Sx, palpitations, rest unremarkable
❖ Gastrointestinal
❖ (+) Nausea/Vomiting, (+) Anorexia, no bleeding, no diarrhea
22
 REVIEW OF SYSTEMS

❖ Genitourinary, Musculoskeletal, Hematologic

❖ unremarkable
❖ Psychiatric
❖ No hallucinations, delusions, depressive s/sx., suicidal ideations
❖ Neurologic
❖ (+) Memory loss, confabulations

23
 ANCILLARY HISTORY

❖ Past Medical
❖ Pulmonary Tuberculosis, completed treatment
❖ Family Medical
❖ Breast CA (maternal)
❖ Obstetric
❖ G3P3 (3003), unremarkable
❖ Personal Social
❖ No vices, recent travel, exposure to toxins
24
 SYSTEMIC EXAMINATION
❖ HEENT:
Anicteric sclera, no cervical lymphadenopathies, no neck mass.
❖ Chest:
No palpable masses, clear breath sounds.
❖ Cardiac:
Regular cardiac rhythm, no murmurs.
❖ Abdomen:
Soft, no palpable masses. No hepatosplenomegaly. Nontender
❖ Extremities:
Fair skinned, (+) wasting on all extremities, no edema.

25
 NEUROLOGIC EXAMINATION
Sensorium: Awake, oriented to person and
Modified MOCA-P: 8
place, and able to follow commands.
Higher Cortical Functions:
No aphasia, no apraxia, no alexia, no left-right
confusion, no hemineglect.
She was able to recall remote events from her
past (birthday, wedding name of husband and two
children) however she had no recollection on the
events during her third pregnancy and her third
child.
26
 NEUROLOGIC EXAMINATION

Modified Fuld-Object Memory Evaluation (FOMET): Below Average

❖ Despite the repeated verbal reminders given

in every trial, she did not recall any objects.
❖ She even did not remember that objects that
was initially shown to her despite a verbal
reminder.
❖ She was able to generate appropriate words in
the rapid verbal retrieval test and word
repetition. 27
 NEUROLOGIC EXAMINATION

No Craniopathies
Extremities:
- Wasting and spasticity on all extremities (upper than lower)
- Flexion deformity of bilateral hands and fingers.

MMTs Reflexes

4 4

4 4

28
 NEUROLOGIC EXAMINATION
Cerebellar: (+) Dysmetria and dysdiadochokinesia not proportional with the lower
leg weakness.
(+) Scanning speech
Sensory: Denies sensory loss to light touch and pinprick.
Joint position and vibration sense: (+) Upper, (-) Lower
Frontal Release Signs: (+) Myerson,
(-) Palmomental, sucking, rooting and grasp reflexes.
Meningeals: (-) Nuchal rigidity, Kernig’s or Brudzinski.
Gait: Severely ataxic gait.

29
 SUMMARY

○ 36/F presenting with memory problems, confabulations, ataxia with a

prior 14-month history of stupor and visual loss preceded by intractable
vomiting on her 6th week of pregnancy.

○ Wasted extremities without edema, anterograde and retrograde amnesia,

below average MOCA-P and FOMET, dysarthria, hyporeflexia, bilateral
extensor toe signs and pancerebellar deficits.

Normal CSF studies, negative serum AntiNMDA-R antibody, 5-7 hz theta

slowing of background activity without epileptiform discharge with T2
hyperintensities on the bilateral anterior thalami, midbrain, and PAG.
30
 QUESTION
What is your primary working impression at this point?

❖Infectious
❖Autoimmune
❖Metabolic
❖Neoplastic
31
32
33
 QUESTION
What is your primary working impression at this point?

❖NMOSD
❖ADEM
❖Wernicke-Korsakoff Syndrome
❖Central pontine and extrapontine
myelinolysis
❖Marchiafava Bignami Disease
34
FINAL DIAGNOSIS

35
 FINAL DIAGNOSIS

Wernicke – Korsakoff Syndrome

from Hyperemesis Gravidarum

36
 FINAL DIAGNOSIS

Wernicke – Korsakoff Syndrome

Wernicke’s Encephalopathy

37
 DEFINITION – Wernicke Encephalopathy
○ Caused by thiamine deficiency
○ Caine criteria.
□ Dietary deficiency
□ Eye signs
□ Cerebellar signs
□ Either an altered mental state or
memory impairment.

Ropper AH, Samuels MA, Klein JP, Prasad S. Adams and Victor’s Principles of Neurology. 11th ed. New York: McGrawHill Education; 2019. 1185–1190 p.
Caine D, Halliday GM, Kril JJ, Harper CG. Operational criteria for the classification of chronic alcoholics: Identification of Wernicke’s encephalopathy. J Neurol Neurosurg psychiatry. 1997;62(1):51–60.
 DEFINITION
Wernicke Korsakoff Syndrome

○ Abnormal mental state

○ Episodic memory is affected out of all proportion
to other cognitive functions
○ Alert and responsive patient

Ropper AH, Samuels MA, Klein JP, Prasad S. Adams and Victor’s Principles of Neurology. 11th ed. New York: McGrawHill Education; 2019. 1185–1190 p.
 FINAL DIAGNOSIS

Wernicke – Korsakoff Syndrome

Wernicke’s Encephalopathy

40
History

Cerebropathia psychica toxaemica

Sergei Korsakoff

Polioencephalitis superior haemorrhagica

Carl Wernicke

Wernicke – Korsakoff Syndrome

Karl Bonhoeffer
History
 RISK FACTORS
❖Decreased availability
❖ Starvation, malnutrition, malabsorption, vomiting

❖Impaired utilization
❖ Decrease enzyme and cofactor activity

❖Accelerated usage
❖ Hypermetabolic state, excess glucose metabolism, rapid cell turnover

❖Increased losses
❖ Iatrogenic
Isenberg-Grzeda E, Kutner HE, Nicolson SE. Wernicke-Korsakoff-Syndrome: Under-recognized and under-treated. Psychosomatics. 2012 Nov;53(6):507–16.
 Manifestations

Ropper AH, Samuels MA, Klein JP, Prasad S. Adams and Victor’s Principles of Neurology. 11th ed. New York: McGrawHill Education; 2019. 1185–1190 p.
Ota Y, Capizzano AA, Moritani T, Naganawa S, Kurokawa R, Srinivasan A. Comprehensive review of Wernicke encephalopathy: pathophysiology, clinical symptoms and imaging findings. Jpn J Radiol [Internet]. 2020 Sep 10;38(9):809–20.
Amnesic State

❖ Anterograde = acquisition
Less efficient coding of contextual information

❖ Retrograde = retrieval
Temporal gradient with relative
preservation of early memories
Temporal gradient

“…the most recently

acquired memories are the
most vulnerable to
disruption from brain
Theodule Ribot
damage. ”
 Pathophysiology

Ota Y, Capizzano AA, Moritani T, Naganawa S, Kurokawa R, Srinivasan A. Comprehensive review of Wernicke encephalopathy: pathophysiology, clinical symptoms and imaging findings. Jpn J Radiol [Internet]. 2020 Sep 10;38(9):809–20.
 Pathophysiology

Thomson AD. The Royal college of physicians report on alcohol: Guidelines for managing wernicke’S encephalopathy in the accident and emergency department. Alcohol Alcohol. 2002 Nov;37(6):513–21.
 Prevention

Hyperemesis Gravidarum = 100mg/day IV

Critically ill Adults = 50-100mg/day IV

ACOG. Clinical management guidelines for obstetrician– gynecologists nausea and vomiting of pregnancy. Am Coll Obstet Gynecol. 2019;133(76):168-186. doi:10.1097/AOG. 0000000000002456
 Treatment

200mg IV three times a day*

(Level C)

❖ No sufficient studies to warrant a formal recommendation.

❖ No evidence to support conclusion to dosage, route and treatment time.
❖ Should be given before any carbohydrate or normal diet is instituted
❖ Treatment should be continued until there is no further improvement in signs
and symptoms.

Galvin R, Bra°then G, Ivashynka A, Hillbom M, Tanasescu R, Leone MA. EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy. Eur J Neurol. 2010;17(12): 1408-1418. doi:10.1111/j.1468-1331.2010.03153.x
Treatment

Magnesium Supplementation
❖ Dose: 2mEq/kg

❖ Co-factor for Thiamine

❖ Refractory cases (Hypomagnesemia)

❖ Contraindication: Addison’s, Myocardial injury, hepatitis, and

hypophosphatemia
Thank you