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HUNGER STRIKE-RELATED WERNICKE-KORSAKOFF’S DISEASE

H.Gürvit, E.Gökmen, D.Kınay, H.Şahin, N.Demirci, R.Tuncay, E.Öge, G.Gürsoy
University of Istanbul,
 Istanbul Faculty of Medicine,
 Dept. of Neurology,
 Istanbul, Turkey

            INTRODUCTION :

            1996 witnessed the longest mass-scale political hunger strike (HS) ever in Turkey.

 

·         May 20, a total of 1500 political prisoners, from 41 different prisons of various provinces of the country started the HS.

 

·         July 3, on the 45th day, the strike was terminated, excluding 220 of them, who remained to carry it on as a “death fasting” (Group 1). 

 

·         HS is ingesting water, salt and lemonade (or linden tea), “death fasting” is limiting daily intake to only 4 glasses of water and salt. 

 

·         July  16 and 23, a further 111 people, who were from the original 1500, joined the death fasters (Groups 2 and 3).  

 

·         July 27, on the 69th day, an agreement was reached and the strike was ended for the entire participants.

 

·         The first death occurred on the 61st and the last one on the last day, making up a total of 12 deaths (11M, 1F), all from the Group 1.

 

 

 

Hunger strikers (n=1500)

 

 

®

 

DEATH

 

Group I: Starts death fasting on the 45th day of HS, up until 69th day.

(n=220)

 

¯

 

 

 

 

First phase as HS  ends after 45 days

(n=1169)

 

FAST

ING

Groups II & III: Terminate HS on 45th day and after an interval of 13 days for Group II and 20 days for Group III, start death fasting for an additional 12 and 5 days, respectively.

(n=111)

 

 

 

 

¯

 

 

 

 

All the groups terminate death fasting on the 69th day.  Group I sufferred 12 deaths

(n=331-12)

 

                                                                                

            PATIENTS :

 

 

·         We have admitted a total of 18 patients (3F, 15M) within the first four weeks, starting right after the termination of the HS.

 

·         16 were from Group 1, one from Group 2, and one had only 39-day history of HS, who upon becoming comatose, had been refed with I.V. glucose, and had become severely amnestic after regaining consciousness.

 

·         14 of the referrals were from Istanbul Bayrampaşa Prison (IBP) which hosted the largest number of strikers (30.9% of Group 1 and 33.3% of the deaths).  One had already been released and the remaining 3 were from the other two prisons in Istanbul.

 

·         17 of 18 admitted patients returned to prison, after 3 to 6 week-hospital stay. One more was released later.

 

·         Via a special access privilege into IBP, we were able to follow up our patients in the prison and had the opportunity to examine the rest of the 60 remaining Group 1 strikers.

 

 

 

TABLE 1 : CONSTITUTIONAL PARAMETERS (n=18)

 

Range (Mean)

Age

23 - 50 (29.9)

Height (cm)

158 - 186 (171.5)

Pre-HS weight (kg)

50 - 105 (69.6)

Post-HS weight (kg)

36 -74 (47.7)

Weight loss (kg)

11 - 31 (21.8)

Post-HS BMI[1](kg/m2)

11.8 - 18.4 (16.5)[2]

 

 

TABLE 2 : MORTALITY AND MORBIDITY OF HS IN IBP*

Deaths

4 (6.25%)

Wernicke-Korsakoff’s

6 (9.37%)

Pure Wernicke’s

33 (51.5%)

Unaffected by W-K

21 (32.8%)

Total

64 (100%)

*Istanbul Bayrampa?a Prison, one of the largest in the country, hosts 30.9% of Group 1 strikers

 

TABLE 3

Main symptoms during the period of starvation

·         Fatigue, weakness, being bedridden mostly after 60th day.

·         Clouding of consciousness

·         Paresthesiae, ‘loss of sensation’, pains and cramps throughout the body.

·         Faintness and syncope in the upright posture.

·         Vomiting, persistent hiccup.

·         Hypersensitivity to light, sound and odors.

·         Decreased vision, double vision.

·         Nocturnal blindness.

·         Tinnitus, hearing loss.

·         Occipital neuralgia-like headache.

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   TABLE 4

 

SYMPTOMS & SIGNS

 

 

INITIAL

# patients

(n=18)

 

 

1ST YEAR

# patients

(n=18)

Altered consciousness (mild confusion to somnolence-stupor)

12

0

Korsakoff-like amnesia

10

10

Apathy

Euphoria, childish behavior

Depression and psychotic behavior

Anxiety Disorder

5

3

2

1

6

0

2

0

Nutritional amblyopia

Decreased vision, pale or blurred optic discs

Retinal hemorrhages

Xerophtalmia

Nocturnal blindness

Conjunctivitis

 

9

2

3

2

 

0

0

0

0

Hypersensitivity to environmental noise

Tinnitus, decreased hearing

Positional vertigo

16

3

2

0

0

0

Horizontal nystagmus

Vertical nystagmus

18

8

18

2

Ophthalmoparesis

12

0

Trunkal ataxia

Limb ataxia

18

4

10

5

Muscle wasting

Muscle weakness

10

5

0

0

Decreased tendon reflexes

5

0

Decreased vibration sensation

Altered position sensation

6

1

0

0

 

SUMMARY OF CLINICAL PICTURE AND THE COURSE

 

 

·         Thiamin replacement was started immediately, along with A, E and B complex vitamins.  Initial refeeding was done via total parental nutrition (TPN), for those whose BMI's were lower than 16.

 

·         Primary sensory problems cleared rapidly, from days to weeks;  although, they were as severe as virtual blindness in some.  Vestibular symptoms were rarer, but most resistant among them.

 

·         Muscle  bulk returned to normal, as the patients started to gain weight.

 

·         All of them showed trunkal ataxia and horizontal nystagmus; accompanied by conjugate gaze or ocular palsies in 12/18. 

?Wernicke's Encephalopathy

 

·         9/10 patients who were stuporous initially, developed a recent memory deficit accompanied by a varying degrees of retrograde amnesia, as their consciousness cleared within days to weeks.

?Wernicke-Korsakoff's Disease

 

·         Remaining 8 patients, 2 of whom were confused initially, did not become amnestic and were classified as Pure Wernicke's.

 

·         Two from the W-K group had psychotic depression initially, and were treated with anti-depressives and one with neuroleptics and ECT.  They improved into an apathetic and amnestic state within 3 months.  Another two, who were pure amnestic initially, developed severe psychiatric pictures after 3 months.  One had a resistant psychotic depression with bipolar features; the other had a delusional disorder.

 

·         Two from the pure W group and another pure W, not included in the group from the prison, after considerable improvement, showed worsening between 3 to 6th months post-HS.  Trunkal ataxia became more marked (mild to moderate) in all, dysarthria and limb ataxia were added in two.  They resumed improvement after 9th month, but with a somewhat slower pace.


 

·         We developed a 7-stage "Activities of Daily Living Scale for Hunger Strikers" in order to follow the course and determine the prognosis of W-K in 1-year period.

TABLE 5

0

-

No symptoms or signs accountable to HS.

 

1

-

Mild symptoms and signs, unrelated to W-K.

 

2a

-

Very mild or residual W (eg. isolated nystagmus).

  2b

-

Mild ataxia, no assistance needed; dysarthria.

 

3

-

Moderate ataxia, walks with assistance; or mild but definite amnesia.

4

-

Severe ataxia, unable to sit unless supported; or prominent amnesia, apathy, depression or psychosis.

5

-

Clouding of consciousness, bedridden.

6

-

Death.

 

 

TABLE 6 : PRESENTATION AND PROGNOSIS

 

GROUPS

Initial Status

1st Year Status

W

Stage 5

4

1

3

0

0

(n=8)

3

4

2

 

2b

a

0

0

3

3

W-K

Stage 5

9

0

 

4

1

7

(n=10)

3

0

3

 

2b

a

0

0

0

0

 


 

         PROGNOSIS

 

 

·         Every single patient, except one from pure W, eventually improved, may be not as satisfactorily as expected.

 

·         In W-K group, 7/9 improved from stage 5  to stage 4, and 2/9 to stage 3.  3/7 who are in stage 4 now are both severely amnestic and atactic, 3/7 is severely amnestic, but mildly atactic, and 1/7 is severely atactic, but mildly amnestic.  Those 3 in stage 3, display mild ataxia and moderate amnesia.

 

·         In Pure W group, 6/8 improved to stage 2b and 2a.  All the three, who are 2a now are female patients.

 

·         The only patient who did not show an overall improvement, is the one who had worsened after the third month and is in stage 3 now.

 

NEUROPSYCHOLOGICAL STUDY :

 

 

·         16 admitted patients are given the battery, within the fourth and sixth week  (initial testing).  Two, from the severe K group were untestable, due to depression and retardation at that time.

 

·         The group was divided into two two subgroups according to having or not having a recent memory problem and they were labeled as Korsakoff’s (acute K, n=8) and pure Wernicke’s (W, n=8) respectively.

 

·         6/8 of the acute K group were available at the 1st year control testing, along with the two, who were untestable at the initial testing (chronic K, n=8).

 

·         K and W subgroups were found to be age  and education matching (28.9±4.2 vs. 30.2±8.6 and 11.6±4.1 vs. 12.1±3.2 respectively).

 

·         The performance of the group W was undiscernable from 21 age and education matched controls (26.3±6.2 and 10.6±3.2).

 

·          K group was poorer on all the memory measures than the W group.  They were also poor on resistance to interference (Stroop), verbal fluency and digit span, but their performance were comparable on mental flexibility (WCST) and visuo-spatial functions.

 

·         No significant improvement was observed in any of the neuropsychological parameters at the 1st year control testing in the K group.

 

 

 


 

TABLE 7 : NEUROPSYCHOLOGICAL BATTERY

ATTENTION

Digit Span

MEMORY

verbal

visual

 

California Verbal Learning Test (CVLT)

The Camden Memory Tests (Warrington) *

Pictorial Recognition Memory Test (CPMRT)

Topographical Recognition Memory Test (CTRMT)

Short Recognition Memory Test for Faces (CSRMT-F)

 

VISUO-SPATIAL

Benton's Line Orientation test (BLO)

Benton's Facial Recognition Test (BFR)

EXECUTİVE

Wisconsin Card Sorting Test (WCST)

Stroop Test

Verbal Fluency (Category Naming)

 

TABLE 8

NEUROPSYCHOLOGICAL COMPARISON OF WERNICKE’S vs. KORSAKOFF’S

 

TEST PARAMETERS

 

W

(n=8)

 

K

 (acute)

(n=8)

 

p value

Digit Span (Fwd + bwd)

12.9±2.0

9.8±1.3

p<.01

CVLT  - # recalled words

A - Trial 1

A - Trial 5

Short Delay Free

Short Delay Cued

Long Delay Free

Long Delay Cued

Recognition Hits

Discriminability

# Perseverations

 

8.4±2.1

13.6±2.9

11.6±3.5

13.5±2.9

12.6±2.6

13.1±2.4

15.5±0.8

96.9±3.5

4.9±3.1

 

6.1±1.6

8.7±3.1

4.0±3.6

7.3±2.3

5.2±3.7

7.2±3.6

12.4±1.8

76.7±13.8

12.0±4.9

 

p<.05

p<.01

p<.001

p<.001

p<.001

p<.01

p<.01

p<.001

p<.01

BLO

23±6

20.9±3.9

NS

BFR

42.5±2.6

39.3±5.9

NS

WCST

# Categories

Conceptual Res. %

# Perseverative Res.

Perseverative Err. %

Set Maintenance

 

5.6±0.7

69.5±12.9

14.1±8.5

12.4±5.1

0.89±0.99

 

4.6±2.0

53.9±22.5

35.4±35.5

25.5±18.1

0.88±1.25

 

NS

NS

NS

NS

NS

Stroop

Interference (sec.)

 

23.4±7.6

 

42.9±22.5

 

p<.05

Verbal Fluency

(# Animals/min.)

 

21.4±4.4

 

14.7±3.2

 

p<.01

 


 

TABLE 9

KORSAKOFF'S INITIAL & FIRST YEAR

COMPARISONS*

 

TEST PARAMETERS

K

(acute)

(n=8)

K

(1st year)

(n=8)

Normative

Values

for Memory Parameters

Digit Span (fwd + bwd)

9.8±1.3

13.9±12.7

 

CVLT

 

 

St. Scores

A-Trial 1

6.1±1.6

5.2±1.4

-2

A-Trial 5

8.7±3.1

9.2±3.1

-5

Short Delay Free

4.0±3.6

5.7±4.1

-4

Short Delay Cued

7.3±2.3

9.1±2.1

-3

Long Delay Free

5.2±3.7

5.0±3.3

-4

Long Delay Cued

7.2±3.6

8.4±3.3

-3

Recognition Hits

12.4±1.8

12.6±3.4

-4

Discriminability

76.7±13.8

82.1±13.0

-2

# Perseverations

12.0±4.9

10.5±7.1

+2

Camden Memory Tests

 

 

%-ile Scores

CPMRT

-

22.1±4.6

1

CTRMT

-

16.4±5.8

1

CSRMT-F

-

19.5±4.4

5

BLO

20±9

20.1±6.4

 

BFR

39.3±5.9

39.1±8.3

 

WCST

 

 

 

# Categories

4.6±2.0

5.1±1.4

 

Conceptual Res. %

53.9±22.5

52.2±23.6

 

# Perseverative Res.

35.4±35.5

26.1±26.0

 

Perseverative Err. %

 

19.0±14.9

 

Set Maintenance

 

0.63±0.52

 

Stroop

 

 

 

Interference (sec)

42.9±22.5

39.4±24.2

 

Verbal Fluency

 

 

 

# Animals/min.

14.7±3.2

16.2±3.6

 

 

 IMAGING STUDY :

 

 

·         An imaging study was designed to see if any finding was specific to  Wernicke-Korsakoff pathology.

 

·         MRI scanning was done by a 1.5T scanner.  Contrast injections were given only in the patient group.

 

·         The scans of 10 age-matched controls, who were scanned for the investigation  of their headache and reported as normal, were intermingled with those of the patients (post-contrast scans were not used for the purpose of this study). 

 

·         Three blinded neuroradiologists rated a certain lesion type as absent, mild or marked.

 

·         Thalamic and third ventricular wall bilaterally, and periaquaductal hyperintensity in T2W images were consistent findings in the patient group.

 

·         Contrast enhancements in third ventricular wall and mamillary bodies were seen in three and two patients respectively.

 

 

 


 

TABLE 10 :        DISCRIMINATIVE MRI FINDINGS of the PATIENT GROUP vs. CONTROLS

 

LESION TYPE

 

Patients

(n = 16)

 

 

Controls*(n = 10)

 

p value

(A)

T2W Thalamic hyperintensity

# Total

Mild

Marked

: 12

: 7

: 5

 

None

 

p<.0005

(B)

T2W Hyperintensity of the 3rd ventricular wall

# Total

Mild

Marked

: 9

: 7

: 2

 

None

 

p<.005

(C)

T2W Hyperintensity of the periaquaductal gray

# Total

Mild

Marked

: 13

: 13

: 0

 

None

 

p<.0005

*Age range 23-50 (mean: 33)

 

Statistical comparison of (A), (B) and (C) type MRI lesions with the W-K subtypes and/or severity of the disease :

·         (A) had a significance among Pure W (n=7), mild K (n=4) and severe K (n=5) groups (p?.017).

 

·         (A) discriminates severe K from pure W (p<.01), but not from mild K, nor mild K from pure W.

 

·         (B) and (C) were not found to be specific for either of the subtypes.

 

STATYSTICS :

SPSS software was used for statistical analyses.  Student-t and Mann-Whitney-U tests were used for even and uneven distributions.

 


Figure 4:

Thalamic hyperintensity in T2W image.

 

Figure 5:

Hyperintensity sorrounding the 3rd

ventricular wall in proton W image.

Figure 3:

Hyperintensity in periaquaductal area

 in proton W image.

Figure 2:

Contrast enhancement sorrounding the 3rd ventricular wall.

Figure 1:

Contrast enhancement on corpora mamillare

TABLE 11 :       ELECTROPHYSIOLOGICAL EXAMINATIONS PERFORMED IN PATIENTS AND AGE-MATCHED CONTROLS

 

STUDIES

 

#

Patients

 

#

Controls

 

STIMULATION

 

RECORDING

SENSORY

ULNAR

15

24

Unilateral

5th finger

Wrist

 

MEDIAN

15

24

Unilateral

2nd finger

Wrist

 

SURAL

15

24

Unilateral

Posterior leg

Lateral malleol

 

MEDIAL

PLANTAR

15

24

Unilateral

1st thumb

Medial malleol

MOTOR

ULNAR

15

24

Bilateral

Wrist, elbow

ADM

 

MEDIAN

15

24

Unilateral

Wrist, elbow

APB

 

TIBIAL

15

24

Unilateral

Ankle, popliteal fossa

AH

 

PERONEAL

15

24

Unilateral

Ankle, fibular head

EDB

F WAVES

ULNAR

15

24

Bilateral

Wrist

ADM

 

MEDIAN

15

24

Unilateral

Wrist

APB

 

TIBIAL

15

24

Unilateral

Ankle

AH

SEP

UPPER

15

16

Unilateral

Median nerve-wrist

Cervical (Cv-FZ)

Cortical (Cc-FZ)

 

LOWER

15

15

Unilateral

Tibial nerve-ankle

Cortical (CZ-Cc)

MEP

UPPER

14

20

Bilateral

Wrist,elbow,axilla (electrical)

cervical, cortical (magnetic)

ADM

 

LOWER

14

21

Bilateral

Lumbar (electrical)

Cortical (magnetic)

TA

BAEP

 

14

20

Bilateral

Rarefaction clicks

(70-85 dB)

Mastoid-CZ

ADM: Abductor digiti minimi, APB: Abductor pollicis brevis ,TA: Tibialis anterior, AH: Abductor hallucis muscles.

 

 

ELECTROPHYSIOLOGICAL STUDY :

 

 

·         Nerve Conduction Velocities (NCV), Somatosensory, Brainstem Auditory, Visual and Motor Evoked Potentials (SEP, BAEP, VEP and MEP respectively), EEG’s and Electro-Retinography (ERG) studies are done.

 

·         Needle EMG was done initially in 3 patients and in 1st year control in 13.

 

·         The results of NCV, SEP, BAEP and MEP studies in comparison to age-matched control subjects and preliminary results of needle EMG  are reported.

 

·         CMAP amplitudes were significantly reduced in ulnar, median and tibial NCV studies.  Median F wave and muscle responses to cervical and lumbar magnetic stimulation had significantly prolonged latencies.  P37 latencies of tibial SEP were prolonged.

 

·         Initial needle EMG were normal.  In the 1st year control  study (first dorsal interosseus, biceps, quadriceps femoris, tibialis anterior and gastrocnemius in all patients): increased insertional activity, pathological spontaneous activity (fasciculations, rhythmic and non-rhythmic positive waves and fibrillation like biphasic potentials), long duration polyphasics in some muscles were found.

 

 



[1]Body Mass Index = weight (kg) / height2 (m) ; lower normal limit for BMI is 20

[2]Excluding one with 22.8 BMI

* Given only to the Korsakoff’s group in the first year control testing.

STATYSTICS : SPSS software was used for statistical analyses.  Student-t and Mann-Whitney-U tests were used for even and uneven distributions.

* None is statistically significant

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