Patients descriptions

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Patients descriptions:
Patient 1 presented with complaints of very brief episodes of sensory disturbance and twitches in
the legs, with altered behaviour and personality changes. Physical neurological examination was
unremarkable. Cognitive assessment revealed impaired memory, worse for verbal than visuospatial
material. Performance fell in the impaired range on the Recognition Memory Test for Words
(<5th%ile, above chance) and at the lower end of the low average range on the visual version (RMT
Faces: 10th%ile). Immediate and delayed recall of a story was extremely reduced (AMIPB Story
recall: <10th%ile). MRI revealed bilateral signal change in the medial temporal lobe, more
prominent in the left hemisphere than the right. A whole body PET scan did not reveal any other
abnormality. CSF analysis did not demonstrate a pleocytosis. VGKC-Ab titre was 3640 pMol/L at
diagnosis, but subsequently fell after intravenous immunoglobulin and then prednisolone. His
neuropsychological and clinical state remains stable two and half years afterwards.
Patient 2 presented with complaints of lapses of memory and blank spells which were considered to
be consistent with seizures. His wife observed that he had poor memory for previous events but also
forgot new things quickly. Physical neurological examination was normal. Neuropsychological testing
revealed variable deficits in memory: verbal scores were in the low average to average (Similarities,
Digit Span) while non-verbal scores varied from borderline (Block Design) to high-average (Picture
Arrangement). Performance on the Recognition Memory Test for Words was intact (50th %ile) while
Recognition Memory for Faces was poor (<5th %ile). Both immediate (50-75th %ile) and delayed
(50th %ile) recall of a story were intact. MRI revealed bilateral signal change in the medial
temporal lobe. VGKC-Ab titre was 1032 pMol/L at diagnosis, but fell after intravenous
immunoglobulin treatment.
Patient 3 presented with confusion and an unwitnessed collapse (presumed to be a generalized
seizure) at home. On hospital admission he was found to have anterograde and retrograde memory
deficits, as well as disorientation to time and place. There were no other symptoms and his
neurological examination was entirely normal. MRI revealed bilateral signal change in the medial
temporal lobes. His CSF was acellular but had elevated protein at 0.7g/dL. A CT of his chest,
abdomen and pelvis was normal. His VGKC-Ab titre was 1935 pMol/L at presentation and fell to
unrecordable levels following intravenous immunoglobulin and high dose prednisolone tapered over
several months. He underwent several assessments of memory all demonstrating deficits in
anterograde and retrograde memory. His clinical condition remains stable in the seven years
following treatment. On recent neuropsychometric assessment he was impaired on several
measures of anterograde memory: WMS-III Logical memory immediate-recall (5th %ile), as well as
delayed-recall (<5th %ile). WMS-III word list was also impaired in immediate-recall (15th %ile) and
delayed-recall (<5th %ile). Recognition Memory Test words was impaired (<5th %ile), as well as for
faces: (10th %ile). Digit span (from the WMS-III) was intact (37th %ile).
Patient 4 presented with a prodrome complex-partial seizures with some limb jerking (up to 40 a
day) followed by an acute onset of confusion, disorientation and amnesia. He was noted at
presentation to have right-sided faciobrachial seizures and there was an emergence of temporal
lobe epilepsy (characterized by déjà vu and a rising sensation from his abdomen). His neurological
examination was entirely normal. Investigations demonstrated an aceullar CSF with a protein of 0.65
0.7g/dL and hyponatraemia (serum sodium 129mmol/L). MRI revealed swelling and high signal of
the left hippocampus. A CT chest, abdomen and pelvis was normal. His VGKC-Ab titre was found to
be 729 pMol/L. He was treated with intravenous immunoglobulins followed by high dose
prednisolone. His seizures were treated with phenytoin, levetiracetam and clobazam which have
been subsequently weaned. His clinical condition remains stable in the 3 years since treatment and
his antibodies are no longer detectable. Formal neuropsychological testing in close proximity to the
time of testing demonstrated no impairment of anterograde or retrograde memory but the patient
complains of subjective memory impairments and a reduced vividness of episodic memories.
Patient 5 was admitted with a three week history of frontal headaches and confusion. He had been
diagnosed with cerebral vasculitis which prompted urgent investigation as an inpatient. His
neurological examination was notable for a long-standing right-sided hemiparesis. Investigations at
that time demonstrated a CSF with a lymphocyte count of 62 and a protein of 1.7 g/dL. MRI
demonstrated several focal white matter lesions in keeping with his previous vasculitis but there was
no evidence of new and specific hippocampal high signal. His VGKC-Ab was raised at 425 pMol/L. In
view of his previous vasculitis he was treated with intravenous methylprednisolone followed by oral
prednisolone whilst awaiting work-up for cyclophosphamide. He has remained clinically stable for
over 6 years and his VGKC-Ab is currently undetectable. Recently he demonstrated severe
impairments in anterograde memory. WMS-III Logical memory was impaired both on immediaterecall (<1th %ile), and delayed-recall (1th %ile). WMS-III word list was also impaired in immediaterecall (<1th %ile) and delayed-recall Z-score (5th %ile). However, his performance on standard
working memory tests seems to be intact: WMS-III digit span Z-score (90th %ile).
Patient 6 presented with jerking of his left shoulder which spread to involve the rest of the arm and
the left leg. There was a suggestion of facial twitching during these episodes as well. His wife then
began to notice that he was becoming forgetful and irritable. Several EEGs were performed which
showed some periodic sharp waves from the temporal lobes. MRI of the brain demonstrated no
medial temporal lobe abnormalities but small vessel disease. A CT chest, abdomen and pelvis was
normal and CSF analysis revealed an acellular CSF with a protein of 0.92g/dL. His VGKC-Ab titre was
elevated at 1735 pMol/L at diagnosis peaking at 1798 four months after diagnosis. He was
commenced on high dose prednisolone but his antibody titre remained persistently raised. Sixmonths following diagnosis he was given concurrent intravenous immunoglobulin after which time
the antibody titre began to fall over a period of a year alongside a resolution in his symptoms.
Antibodies are currently undetectable and he has been clinically stable since this time. Recent
neuropsychometric assessment showed deficits in anterograde memory: WMS-III Logical memory
immediate-recall (15th %ile), delayed-recall: (<1th %ile). However no deficits in standard working
memory tasks were observed: WMS-III digit span (50th %ile).
Patient 7 presented with a two day history of disorientation which culminated in generalized tonicclonic seizures. Following treatment she recounted that she had experienced increasing sensations
of déjà vu prior to her disorientation and collapse. Prior to the confusion there were no specific
memory complaints. Her neurological examination was normal. Investigations found a normal CSF
with no other biochemical abnormalities. Her MRI demonstrated bilateral medial temporal lobe high
signal. A CT chest, abdomen and pelvis was normal. She was treated with intravenous
immunoglobulins followed by oral prednisolone, which has been subsequently discontinued. She has
remained clinically stable since this time. Formal recent neuropsychometry demonstrates problems
only with the delayed-recall of the WMS-III logical memory (5th %ile). Her performance on standard
working memory tasks was normal.
Raw scores in experiments 1 & 2:
Tests
Exp
1
Exp
2
Controls (SD)
Patients (SD)
1
2
3
4
5
6
7
Identification
Number of
items
1 item
0.99 (0.01)
0.98 (0.03)
0.95
1
0.95
1
1
0.95
1
performance
3 items
0.85 (0.1)
0.81 (0.05)
0.7
0.84
0.84
0.83
0.83
0.83
0.8
Localization
1 item
2.5 (1.2)
2.8 (0.72)
2.9
2.3
2.8
4.2
3.2
2.3
2.1
error
3 items
7.4 (2.5)
10.4 (2.3)
12.2
9.4
8.6
14.7
10.5
8.6
9
Nearest item control
3 items
4.3 (1.5)
4.4 (0.7)
3.9
3.8
3.7
5.3
5.3
4.4
4
Percent of swap errors
3 items
11 (4)
21 (3)
21
25
19
24
17
18
22
Swaps minus chance
3 items
7 (4)
13 (4)
12
18
12
13
9
12
13
Angular
1 item
12.8 (3.9)
11.3 (0.5)
11.1
10.9
11.8
error
2 items
17.5 (2.8)
21.4 (3.5)
24.6
22.9
16.6
to target
3 items
19.7 (4.2)
25.3 (2.3)
27.5
22.2
26.1
Percentage of trials
0-30 deg
31 (2.8)
38 (3.8)
43
35
35
with angular error
30-60 deg
34 (3.1)
32 (1.4)
30
33
33
to NON targets
60-90 deg
35 (3.5)
30 (2.5)
27
32
32
Angular
1 item
12.8 (3.9)
11.3 (0.5)
11.1
10.9
11.8
error
2 items
13.4 (2.7)
15.6 (1.7)
15.3
17.4
14.1
to nearest item
3 items
11.7 (2.0)
12.3 (0.7)
12.2
11.7
13.1
Supplemental Table s1. Group and individual performance in experiments 1 & 2
Averaged raw scores and standard deviation (in brackets) of controls and patients performance in
experiments 1 & 2 for the different conditions. Rightmost columns describe the raw scores of the
individual patients 1 to 7. Identification performance is in proportion correct. Localization and
angular errors are in degrees and swap errors are in percentage of trials.
Visual stimuli:
Supplemental Figure s1. Visual stimuli used in experiment 1.
60 colored fractals on black background were used. Symmetrical fractals were generated using code
provided in Sprott's Fractal Gallery (http://sprott.physics.wisc.edu/fractals.htm). Fractals were
resized to have maximum width and height of 120 pixels (~4 degrees of visual angle in experimental
set-up).
Serial position effects on swap errors in experiment 2.
Supplemental Figure s2. Swap errors with respect to target's serial position.
We analyzed the number of swap errors in 3-item sequences (as percentages of trials) with respect
to the target's serial position in the sequence. We statistically analyzed these results using a mixed
ANOVA with serial-position as within subjects factor and group (patients vs controls) as between
subjects factor. Consistent with previous findings (Gorgoraptis et al 2011 J Neurosci) the ANOVA
revealed a significant effect of serial position (F(2,18) = 5.2, p = .04, ηp2 = 0.56). The effect of group
was also significant (F(1,9) = 7.3, p = .02, ηp2 = 0.45), but not the interaction (F(2,18) = 0.8, p = .45,
ηp2 = 0.08). We conclude that, in general, more swap errors were made when subjects were asked
to report on items that were presented early in the sequence. This trend seems to be slightly
exaggerated in patients; their additional swap errors seem to arise mainly from items displayed early
in the sequence, but this difference is not strong enough to be reflected in the ANOVA. Patients, in
general, exhibit higher number of swap errors than controls, consistent with the analysis in the main
text.
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