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HUNGER STRIKE-RELATED WERNICKE-KORSAKOFF’S DISEASE
H.Gürvit,
E.Gökmen, D.Kýnay, H.Þahin, 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. |
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·
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). |
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·
HS is ingesting water, salt and
lemonade (or linden tea), “death fasting” is limiting daily intake to only 4 glasses
of water and salt. |
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·
July 16 and 23, a further 111 people, who were from the
original 1500, joined the death fasters (Groups 2 and 3).
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·
July 27, on the 69th
day, an agreement was reached and the strike was ended for the entire participants. |
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·
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.
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Hunger strikers (n=1500)
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®
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DEATH |
Group I: Starts death fasting on the 45th
day of HS, up until 69th day.
(n=220)
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¯ |
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First
phase as HS
ends after 45 days
(n=1169) |
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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)
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¯ |
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All the groups terminate death fasting on
the 69th day. Group I sufferred 12 deaths
(n=331-12)
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PATIENTS :
·
We have admitted a total of 18
patients (3F, 15M) within the first four weeks, starting right after the termination of
the HS. |
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·
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 Bayrampaþa 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. |
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·
17 of 18 admitted patients
returned to prison, after 3 to 6 week-hospital stay. One more was released later. |
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·
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.
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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(kg/m2) |
11.8 -
18.4 (16.5) |
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%) |
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. |
.
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. |
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·
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. |
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·
Muscle bulk returned to normal, as the patients started
to gain weight. |
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All of them showed trunkal
ataxia and horizontal nystagmus; accompanied by conjugate gaze or ocular palsies in 12/18. |
?Wernicke's Encephalopathy |
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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 |
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·
Remaining 8 patients, 2 of whom
were confused initially, did not become amnestic and were classified as Pure Wernicke's. |
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·
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. |
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·
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. |
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·
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. |
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·
In Pure W group, 6/8 improved
to stage 2b and 2a. All the three, who are 2a
now are female patients. |
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·
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.
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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. |
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·
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. |
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·
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). |
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·
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). |
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The performance of the group W
was undiscernable from 21 age and education matched controls (26.3±6.2 and 10.6±3.2). |
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·
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. |
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·
No significant improvement was
observed in any of the neuropsychological parameters at the 1st year control testing in
the K group.
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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) |
EXECUTÝVE |
Wisconsin
Card Sorting Test (WCST)
Stroop
Test
Verbal
Fluency (Category Naming) |
TABLE 8
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) |
|
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 |
|
20.1±6.4 |
|
BFR |
|
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 |
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IMAGING STUDY :
·
An imaging study was designed
to see if any finding was specific to Wernicke-Korsakoff
pathology. |
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·
MRI scanning was done by a 1.5T
scanner. Contrast injections were given only
in the patient group. |
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·
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). |
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·
Three blinded neuroradiologists
rated a certain lesion type as absent, mild or marked. |
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·
Thalamic and third ventricular
wall bilaterally, and periaquaductal hyperintensity in T2W images were consistent findings
in the patient group. |
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·
Contrast enhancements in third
ventricular wall and mamillary bodies were seen in three and two patients respectively.
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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). |
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(A) discriminates severe K from
pure W (p<.01), but not from mild K, nor mild K from pure W. |
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(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 |
|
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. |
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·
Needle EMG was done initially
in 3 patients and in 1st year control in 13. |
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·
The results of NCV, SEP, BAEP
and MEP studies in comparison to age-matched control subjects and preliminary results of
needle EMG are reported. |
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·
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. |
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·
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.
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STATYSTICS : SPSS software was used for
statistical analyses. Student-t and
Mann-Whitney-U tests were used for even and uneven distributions.
|
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