- Email: [email protected]
Functional Impairments in a Patient with Morvan Syndrome: A Case Presentation
Accepted Manuscript The Functional Impairments in a Patient with Morvan’s Syndrome: A Case Report Stephanie Tow, MD, Desi Carozza, MD, Kim Barker, MD PII:
S1934-1482(17)30143-0
DOI:
10.1016/j.pmrj.2017.10.014
Reference:
PMRJ 2027
To appear in:
PM&R
Received Date: 22 February 2017 Revised Date:
18 October 2017
Accepted Date: 25 October 2017
Please cite this article as: Tow S, Carozza D, Barker K, The Functional Impairments in a Patient with Morvan’s Syndrome: A Case Report, PM&R (2018), doi: 10.1016/j.pmrj.2017.10.014. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
M AN U
Desi Carozza, MD Center for Connected Care Cleveland Clinic 6801 Brecksville Road, Suite 10/RK30 Independence, OH 44131 Phone: 216-636-8742 Fax: 216-636-7877 Email: [email protected]
SC
Authors: Stephanie Tow, MD Department of Pediatric Rehabilitation Medicine Children’s Hospital Colorado University of Colorado Anschutz Medical Center 13123 East 16th Avenue, Box 285 Aurora, CO 80045 Phone: 720-777-5214 Fax: 720-777-7297 Email: [email protected]
RI PT
Title: The Functional Impairments in a Patient with Morvan’s Syndrome: A Case Report
TE D
Kim Barker, MD Department of Physical Medicine & Rehabilitation University of Texas Southwestern Medical Center 5323 Harry Hines Blvd, Dallas, TX 75390-9055 Phone: 214-648-8778 Fax: 214-648-9207 Email: [email protected]
EP
This case report was presented at the AAPM&R Annual Assembly 2016 in New Orleans, LA.
AC C
Funding Source: N/A (Case report)
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ACCEPTED MANUSCRIPT
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The Functional Impairments in a Patient with Morvan’s Syndrome: A Case Report
ACCEPTED MANUSCRIPT
Abstract
2
A 48 year-old man with lung squamous cell carcinoma was admitted to acute care with cognitive
3
impairment after recent chemotherapy. He developed myoclonus, ataxia, agitation, and visual
4
hallucinations. Morvan’s Syndrome, a rare voltage-gated potassium channel antibody disorder
5
characterized by neuromyotonia with central nervous system dysfunction, was eventually
6
diagnosed. He received plasmapheresis and was admitted to inpatient rehabilitation, where he
7
safely participated in therapies. By focusing on neuromuscular rehabilitation, balance training, fine
8
motor skills, and cognitive retraining emphasizing skills relevant to the patient’s premorbid
9
cognitive activities, the patient demonstrated significant functional improvement, decreasing the
SC
burden of care of his caregivers.
11 12
16 17 18 19 20 21
EP
15
AC C
14
TE D
13
M AN U
10
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1
22 23
2
ACCEPTED MANUSCRIPT
Introduction
25
Morvan’s Syndrome is a rare autoimmune disease associated with auto-antibodies to voltage-
26
gated potassium channels (VGKC) and involves the peripheral nervous system, autonomic system,
27
and central nervous system [1]. It encompasses a wide array of neurological symptoms, including
28
neuromyotonia, pain, hyperhidrosis, severe constipation, urinary incontinence, cardiac
29
arrhythmia, pruritis, weight loss, severe insomnia, hallucinations, short-term memory impairment,
30
and epilepsy [2]. The disease has been associated with thymoma, tumor, and autoimmune
31
diseases, which suggests an autoimmune or paraneoplastic etiology [3]. Different antibody targets,
32
including contactin-associated protein 2 (CASPR2), leucine-rich glioma inactivated 1 (LGI1), and
33
contactin-2 have been associated with specific clinical syndromes, each with its own set of
34
features and prognosis [1]. In addition to these lab findings, electromyography (EMG) findings may
35
demonstrate spontaneous, repetitive motor unit or single fiber discharges that fire in irregular
36
rhythmic bursts at high intraburst frequencies [3]. Treatment options often involve plasmapheresis
37
with or without steroids, treatment of the underlying condition (e.g. thymectomy), and chronic
38
immunosuppression, but variable effects of these treatments have been reported [3-4]. However
39
there are no reports on Morvan’s Syndrome and treatment with intensive rehabilitation.
42 43 44
SC
M AN U
TE D
EP
41
AC C
40
RI PT
24
45 46
3
ACCEPTED MANUSCRIPT
Case Report
48
A 48 year-old man who was a software engineer was recently diagnosed with stage 4 squamous
49
cell carcinoma (SCC) of the lung and was admitted to the acute care hospital of an academic
50
medical center for impaired cognitive status. He had recently been treated with one cycle of
51
carboplatin and paclitaxel, as well as started on opioids for pleuritic, tumor-related chest pain. It
52
was originally thought that the patient’s cognitive impairment was due to medication side effects
53
of opioid pain management. However, despite stopping his opioid medications, there was no
54
improvement in his cognition. Several days after admission, he was noted to develop myoclonus
55
and ataxia. He also developed agitation, visual hallucinations, short-term memory impairment,
56
seizures, insomnia, hyperhidrosis, and weight loss. During his hospitalization, he did not have any
57
symptoms of severe constipation, urinary incontinence, cardiac arrhythmia, or pruritis, which may
58
be present in other patients with Morvan’s Syndrome and may further complicate the
59
rehabilitation course if present. Imaging of his brain, complete blood count, and comprehensive
60
metabolic panel were unremarkable. There were no signs of infection causing delirium. Numerous
61
electroencephalograms (EEGs) were negative for seizure activity. Nerve conduction study (NCS)
62
and EMG were performed and only notable for fasciculations. Extensive encephalopathy work-up,
63
including infectious, metabolic, paraneoplastic, and autoimmune encephalopathy panels (see
64
Table 1), demonstrated positive findings for VGKC antibody, as well as well CASPR2 and LGI1
65
antibodies. These are all indicative of Morvan’s Syndrome, a variant of a voltage-gated potassium
66
channel antibody disorder characterized by neuromyotonia in the setting of central nervous
67
system dysfunction.
AC C
EP
TE D
M AN U
SC
RI PT
47
68
4
ACCEPTED MANUSCRIPT
The patient was treated with intravenous solumedrol with no clinical change. He was then started
70
on plasmapharesis with improvement in various functional areas: His agitation prior to the
71
plasmapharesis was difficult to control and anti-psychotics (including atypicals and haloperidol)
72
caused a paradoxical effect. Prior to initiation of plasmapheresis, the patient’s cognitive status was
73
noted to be grossly severely impaired with Montreal Cognitive Assessment (MOCA) [5] score less
74
than 10. After initiation of plasmapheresis on hospital day (HD) 33, his hallucinations stopped, and
75
he progressed from severe cognitive impairment to moderate on the MOCA (see Table 2). He also
76
demonstrated improvement in some of his Functional Independence Measure (FIM) instrument
77
scores [6], mainly in cognition, but also with transfers, lower extremity dressing, and bathing (see
78
Table 3). Prior to PM&R consult on HD 35, the patient was noted to be dependent with all ADLs.
79
After plasmapharesis, he no longer required one-on-one observation or restraints for his safety.
80
This allowed him to participate in physical and occupational therapy in the acute care stage of
81
hospitalization, where he progressed from dependent for all basic activities of daily living (ADLs) to
82
a variable maximal to minimal assistance for basic ADLs upon completion of plasmapharesis (see
83
Table 3). He was then discharged from acute care to inpatient rehabilitation.
SC
M AN U
TE D
EP
84
RI PT
69
During his inpatient rehabilitation course, physical and occupational therapies focused on
86
neuromuscular rehabilitation, balance training, and fine motor skills with frequent verbal cueing
87
by therapists, especially when the patient had a few episodes of visual hallucinations. Given his
88
premorbid functional status as a software engineer, cognitive retraining mainly focused on higher
89
level executive functioning in reading comprehension, math, and finance skills. The patient had
90
strong and reliable family support, with his wife often available in the rehabilitation unit to assist
91
with encouragement and reorientation. This also allowed for appropriate family training to ensure
AC C
85
5
ACCEPTED MANUSCRIPT
92
safe transition to home, while also embracing continuity of his rehabilitation plan to optimize
93
functional status at home.
RI PT
94 He continued to progress on the inpatient rehabilitation unit, and eventually at the time of
96
discharge home, he was at supervision level for ambulation, transfers, and self-care ADLs (see
97
Table 3). In regards to his cognition, MOCA demonstrated normal cognitive status (see Table 2),
98
but FIM scores demonstrated a mildly higher level of cognitive impairment at time of discharge
99
home (see Table 3). His inpatient rehabilitation course was complicated by seizure activity that
M AN U
SC
95
required a transfer back to acute care, where he continued to receive physical, occupational, and
101
speech therapies, at which point he was discharged home with outpatient physical and speech
102
therapies. At home, his visual hallucinations waxed and waned but were overall controlled with
103
chronic immunosuppression via mycophenolate mofetil and prednisone, along with supportive
104
care. He continued to have occasional hallucinations and difficulty with higher level cognitive
105
processing. However, during outpatient follow-up visits, he was ambulating independently without
106
an assistive device. His records were also sent to a tertiary cancer center for second opinion; the
107
repeat pathology results were consistent with thymic malignancy and not squamous cell
108
carcinoma. Oncology followed the patient outpatient; further treatment options of the thymic
109
malignancy were limited by his poor performance status and anticipated poor treatment
110
tolerance.
112
EP
AC C
111
TE D
100
113 114
6
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Discussion
116
To date, few cases of Morvan’s Syndrome have been reported in the English literature. These
117
reports have discussed medical interventions such as treatment with steroids, plasmapheresis, or
118
treatment of the underlying condition (e.g. thymectomy) [1-4]. However no reports have been
119
published discussing rehabilitation interventions and their effects on functional outcomes in
120
patients with Morvan’s Syndrome. This is especially relevant for patients who have limitations in
121
treatment of their underlying condition but still have significant functional impairments causing
122
decreased independence and increased caregiver burden of care, such as was the case with the
123
patient discussed in this report. This case demonstrated that a patient with significant functional
124
impairments secondary to Morvan’s Syndrome was able to make significant functional gains after
125
working with physical, occupational, and speech therapies in an academic hospital inpatient
126
rehabilitation unit.
M AN U
SC
RI PT
115
TE D
127
In particular, a focus on neuromuscular rehabilitation, balance training, fine motor skills with
129
frequent verbal cueing in the context of strong family support allowed the patient to optimize
130
function with mobility and ADLs. Furthermore, the patient’s premorbid high executive functioning
131
cognitive status also may have increased his chances of improved cognitive recovery with
132
rehabilitation. While some of the patient’s FIM scores were unchanged or did not show significant
133
improvement from admission to discharge from acute inpatient rehabilitation, it is important to
134
note that the patient was discharged prematurely for seizures requiring acute care management
135
that could not be managed on the rehabilitation unit. This change in medical status most likely
136
impacted his FIM scores on day of discharge from the rehabilitation unit. Once medically
137
stabilized, he continued to demonstrate improvement in his FIM scores in acute care using the
AC C
EP
128
7
ACCEPTED MANUSCRIPT
same techniques used in inpatient rehabilitation. Overall, the intensive rehabilitation he received
139
improved his level of independence and decreased the burden of care required by his caregivers,
140
as subjectively reported by the patient’s wife, on discharge home.
RI PT
138
141
Information on how patients with Morvan’s Syndrome who receive definitive treatment for their
143
underlying condition perform in rehabilitation has not been commented upon in the medical
144
literature. This case report was limited to evaluation of rehabilitation in the acute care and
145
inpatient rehabilitation settings of an academic hospital. Further studies could evaluate the effects
146
of different rehabilitation settings (e.g. skilled nursing facilities, outpatient therapies, etc) on
147
functional progress in a patient with Morvan’s Syndrome.
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148 149
153 154 155 156 157 158
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159 160
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References
162
1. Liguori R, Vincent A, Clover L, et al. Morvan’s syndrome: peripheral and central nervous system
163
and cardiac involvement with antibodies to voltage-gated potassium channels. Brain 2001; 124(Pt
164
12):2417-2426.
165
2. Misawa T, Mizusawa H. Anti-VGKC antibody-associated limbic encephalitis/Morvan syndrome.
166
Brain Nerve 2010; 62(4):339-345.
167
3. Lee EK, Maselli RA, Ellis WG, Agius MA. Morvan’s fibrillary chorea: a paraneoplastic
168
manifestation of thymoma. J Neurol Neurosurg Psychiatry 1998; 65:857-862.
169
4. Galié E, Renna R, Plantone D, et al Paraneoplastic Morvan’s syndrome following surgical
170
treatment of recurrent thymoma: A case report. Oncol Lett 2016; 12(4):2716-2719
171
5. Nasreddine, Z. Montreal Cognitive Assessment: MOCA Test Full 7.1 English. Electronic test,
172
August 2010. Available at External link http://www.mocatest.org/electronic-tests/. Accessed
173
August 20, 2017.
174
6. Uniform Data System for Medical Rehabilitation. The FIM Instrument: Its Background, Structure,
175
and Usefulness. Adobe Portable Document Format, 2012. Available at External link
176
https://www.udsmr.org/Documents/The_FIM_Instrument_Background_Structure_and_Usefulnes
177
s.pdf. Accessed August 20, 2017.
179 180 181
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182 183
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Result
Lab
Result
Anti-VGKC Ab
Positive
HIV
Negative
Anti-CASPR2 Ab
Positive
HSV
Negative
Anti-LGI1 Ab
Positive
RPR
Negative
NMDA-R-Ab
Negative
VZV PCR
Negative
Thiamine
62 (Low)
ANNA 1, 2, 3
Negative
Vitamin B12
554 (Normal)
PCA 1, 2, 3
Negative
TSH
2.06 (Normal)
Thyroglobulin
Negative
Heavy Metals
Negative
Thyroid Peroxidase
Negative
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Lab
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Tables
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Table 1: Selected lab results included in the work-up of this patient leading to diagnosis of
186
Morvan’s Syndrome.
187
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185
Ab = antibody; NMDA-R-Ab = N-methyl-D-aspartate receptor antibody; TSH = thyroid-stimulating
189
hormone; HIV = human immunodeficiency virus; HSV = herpes simplex virus; RPR = rapid plasma
190
reagin; VZV PCR = varicella-zoster virus polymerase chain reaction; ANNA 1, 2, 3 = anti-neuronal
191
nuclear antibodies 1, 2, 3; PCA 1, 2, 3 = purkinje cell cytoplasmic antibodies 1, 2, 3.
193 194
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192
EP
188
195 196 197
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SC
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MOCA Test Scores (Points Scored/Total Possible Points) Admission to Discharge from Acute Acute Inpatient Care to Home Rehabilitation (HD 52) (HD 39) Visuospatial/Executive 2/5 5/5 Naming 2/3 2/3 Attention 1/6 6/6 Language 1/3 3/3 Abstraction 2/2 1/2 Delayed Recall 5/5 5/5 Orientation 4/6 6/6 TOTAL 17/30 28/30 Table 2: MOCA scores during different time points in patient’s hospital course.
199 200 201
205 206 207 208 209 210
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204
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203
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202
211 212 213
11
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FIM Scores Admission to Acute Inpatient Rehabilitation (HD 38)
Discharge from Acute Inpatient Rehabilitation (HD 45)
Discharge from Acute Care (HD 54)
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Initial PM&R Consult While in Acute Care (HD 35) 1 5 5 4 2 5 2 2 2 2
215
UE = upper extremity; LE = lower extremity; WC=wheelchair.
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Bladder 1 6 6 Bowel 6 6 6 Eating 5 7 7 Grooming 2 5 5 Bathing 4 4 5 UE Dressing 5 5 6 LE Dressing 4 5 6 Toileting 2 5 5 Toilet Transfer 2 4 5 Tub/Shower 4 4 5 Transfer Bed/Chair/WC 2 2 2 6 Transfer Walk/WC mobility 4 (walk) 1/5 1/5 5/5 Stairs 1 1 3 3 Comprehension 2 3 6 6 Expression 2 3 5 7 Social Interaction 2 5 5 6 Problem Solving 1 2 2 5 Memory 1 2 2 5 Table 3: FIM instrument scores during various time points in patient’s hospital course.
12
S1934-1482(17)30143-0
DOI:
10.1016/j.pmrj.2017.10.014
Reference:
PMRJ 2027
To appear in:
PM&R
Received Date: 22 February 2017 Revised Date:
18 October 2017
Accepted Date: 25 October 2017
Please cite this article as: Tow S, Carozza D, Barker K, The Functional Impairments in a Patient with Morvan’s Syndrome: A Case Report, PM&R (2018), doi: 10.1016/j.pmrj.2017.10.014. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
M AN U
Desi Carozza, MD Center for Connected Care Cleveland Clinic 6801 Brecksville Road, Suite 10/RK30 Independence, OH 44131 Phone: 216-636-8742 Fax: 216-636-7877 Email: [email protected]
SC
Authors: Stephanie Tow, MD Department of Pediatric Rehabilitation Medicine Children’s Hospital Colorado University of Colorado Anschutz Medical Center 13123 East 16th Avenue, Box 285 Aurora, CO 80045 Phone: 720-777-5214 Fax: 720-777-7297 Email: [email protected]
RI PT
Title: The Functional Impairments in a Patient with Morvan’s Syndrome: A Case Report
TE D
Kim Barker, MD Department of Physical Medicine & Rehabilitation University of Texas Southwestern Medical Center 5323 Harry Hines Blvd, Dallas, TX 75390-9055 Phone: 214-648-8778 Fax: 214-648-9207 Email: [email protected]
EP
This case report was presented at the AAPM&R Annual Assembly 2016 in New Orleans, LA.
AC C
Funding Source: N/A (Case report)
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
The Functional Impairments in a Patient with Morvan’s Syndrome: A Case Report
ACCEPTED MANUSCRIPT
Abstract
2
A 48 year-old man with lung squamous cell carcinoma was admitted to acute care with cognitive
3
impairment after recent chemotherapy. He developed myoclonus, ataxia, agitation, and visual
4
hallucinations. Morvan’s Syndrome, a rare voltage-gated potassium channel antibody disorder
5
characterized by neuromyotonia with central nervous system dysfunction, was eventually
6
diagnosed. He received plasmapheresis and was admitted to inpatient rehabilitation, where he
7
safely participated in therapies. By focusing on neuromuscular rehabilitation, balance training, fine
8
motor skills, and cognitive retraining emphasizing skills relevant to the patient’s premorbid
9
cognitive activities, the patient demonstrated significant functional improvement, decreasing the
SC
burden of care of his caregivers.
11 12
16 17 18 19 20 21
EP
15
AC C
14
TE D
13
M AN U
10
RI PT
1
22 23
2
ACCEPTED MANUSCRIPT
Introduction
25
Morvan’s Syndrome is a rare autoimmune disease associated with auto-antibodies to voltage-
26
gated potassium channels (VGKC) and involves the peripheral nervous system, autonomic system,
27
and central nervous system [1]. It encompasses a wide array of neurological symptoms, including
28
neuromyotonia, pain, hyperhidrosis, severe constipation, urinary incontinence, cardiac
29
arrhythmia, pruritis, weight loss, severe insomnia, hallucinations, short-term memory impairment,
30
and epilepsy [2]. The disease has been associated with thymoma, tumor, and autoimmune
31
diseases, which suggests an autoimmune or paraneoplastic etiology [3]. Different antibody targets,
32
including contactin-associated protein 2 (CASPR2), leucine-rich glioma inactivated 1 (LGI1), and
33
contactin-2 have been associated with specific clinical syndromes, each with its own set of
34
features and prognosis [1]. In addition to these lab findings, electromyography (EMG) findings may
35
demonstrate spontaneous, repetitive motor unit or single fiber discharges that fire in irregular
36
rhythmic bursts at high intraburst frequencies [3]. Treatment options often involve plasmapheresis
37
with or without steroids, treatment of the underlying condition (e.g. thymectomy), and chronic
38
immunosuppression, but variable effects of these treatments have been reported [3-4]. However
39
there are no reports on Morvan’s Syndrome and treatment with intensive rehabilitation.
42 43 44
SC
M AN U
TE D
EP
41
AC C
40
RI PT
24
45 46
3
ACCEPTED MANUSCRIPT
Case Report
48
A 48 year-old man who was a software engineer was recently diagnosed with stage 4 squamous
49
cell carcinoma (SCC) of the lung and was admitted to the acute care hospital of an academic
50
medical center for impaired cognitive status. He had recently been treated with one cycle of
51
carboplatin and paclitaxel, as well as started on opioids for pleuritic, tumor-related chest pain. It
52
was originally thought that the patient’s cognitive impairment was due to medication side effects
53
of opioid pain management. However, despite stopping his opioid medications, there was no
54
improvement in his cognition. Several days after admission, he was noted to develop myoclonus
55
and ataxia. He also developed agitation, visual hallucinations, short-term memory impairment,
56
seizures, insomnia, hyperhidrosis, and weight loss. During his hospitalization, he did not have any
57
symptoms of severe constipation, urinary incontinence, cardiac arrhythmia, or pruritis, which may
58
be present in other patients with Morvan’s Syndrome and may further complicate the
59
rehabilitation course if present. Imaging of his brain, complete blood count, and comprehensive
60
metabolic panel were unremarkable. There were no signs of infection causing delirium. Numerous
61
electroencephalograms (EEGs) were negative for seizure activity. Nerve conduction study (NCS)
62
and EMG were performed and only notable for fasciculations. Extensive encephalopathy work-up,
63
including infectious, metabolic, paraneoplastic, and autoimmune encephalopathy panels (see
64
Table 1), demonstrated positive findings for VGKC antibody, as well as well CASPR2 and LGI1
65
antibodies. These are all indicative of Morvan’s Syndrome, a variant of a voltage-gated potassium
66
channel antibody disorder characterized by neuromyotonia in the setting of central nervous
67
system dysfunction.
AC C
EP
TE D
M AN U
SC
RI PT
47
68
4
ACCEPTED MANUSCRIPT
The patient was treated with intravenous solumedrol with no clinical change. He was then started
70
on plasmapharesis with improvement in various functional areas: His agitation prior to the
71
plasmapharesis was difficult to control and anti-psychotics (including atypicals and haloperidol)
72
caused a paradoxical effect. Prior to initiation of plasmapheresis, the patient’s cognitive status was
73
noted to be grossly severely impaired with Montreal Cognitive Assessment (MOCA) [5] score less
74
than 10. After initiation of plasmapheresis on hospital day (HD) 33, his hallucinations stopped, and
75
he progressed from severe cognitive impairment to moderate on the MOCA (see Table 2). He also
76
demonstrated improvement in some of his Functional Independence Measure (FIM) instrument
77
scores [6], mainly in cognition, but also with transfers, lower extremity dressing, and bathing (see
78
Table 3). Prior to PM&R consult on HD 35, the patient was noted to be dependent with all ADLs.
79
After plasmapharesis, he no longer required one-on-one observation or restraints for his safety.
80
This allowed him to participate in physical and occupational therapy in the acute care stage of
81
hospitalization, where he progressed from dependent for all basic activities of daily living (ADLs) to
82
a variable maximal to minimal assistance for basic ADLs upon completion of plasmapharesis (see
83
Table 3). He was then discharged from acute care to inpatient rehabilitation.
SC
M AN U
TE D
EP
84
RI PT
69
During his inpatient rehabilitation course, physical and occupational therapies focused on
86
neuromuscular rehabilitation, balance training, and fine motor skills with frequent verbal cueing
87
by therapists, especially when the patient had a few episodes of visual hallucinations. Given his
88
premorbid functional status as a software engineer, cognitive retraining mainly focused on higher
89
level executive functioning in reading comprehension, math, and finance skills. The patient had
90
strong and reliable family support, with his wife often available in the rehabilitation unit to assist
91
with encouragement and reorientation. This also allowed for appropriate family training to ensure
AC C
85
5
ACCEPTED MANUSCRIPT
92
safe transition to home, while also embracing continuity of his rehabilitation plan to optimize
93
functional status at home.
RI PT
94 He continued to progress on the inpatient rehabilitation unit, and eventually at the time of
96
discharge home, he was at supervision level for ambulation, transfers, and self-care ADLs (see
97
Table 3). In regards to his cognition, MOCA demonstrated normal cognitive status (see Table 2),
98
but FIM scores demonstrated a mildly higher level of cognitive impairment at time of discharge
99
home (see Table 3). His inpatient rehabilitation course was complicated by seizure activity that
M AN U
SC
95
required a transfer back to acute care, where he continued to receive physical, occupational, and
101
speech therapies, at which point he was discharged home with outpatient physical and speech
102
therapies. At home, his visual hallucinations waxed and waned but were overall controlled with
103
chronic immunosuppression via mycophenolate mofetil and prednisone, along with supportive
104
care. He continued to have occasional hallucinations and difficulty with higher level cognitive
105
processing. However, during outpatient follow-up visits, he was ambulating independently without
106
an assistive device. His records were also sent to a tertiary cancer center for second opinion; the
107
repeat pathology results were consistent with thymic malignancy and not squamous cell
108
carcinoma. Oncology followed the patient outpatient; further treatment options of the thymic
109
malignancy were limited by his poor performance status and anticipated poor treatment
110
tolerance.
112
EP
AC C
111
TE D
100
113 114
6
ACCEPTED MANUSCRIPT
Discussion
116
To date, few cases of Morvan’s Syndrome have been reported in the English literature. These
117
reports have discussed medical interventions such as treatment with steroids, plasmapheresis, or
118
treatment of the underlying condition (e.g. thymectomy) [1-4]. However no reports have been
119
published discussing rehabilitation interventions and their effects on functional outcomes in
120
patients with Morvan’s Syndrome. This is especially relevant for patients who have limitations in
121
treatment of their underlying condition but still have significant functional impairments causing
122
decreased independence and increased caregiver burden of care, such as was the case with the
123
patient discussed in this report. This case demonstrated that a patient with significant functional
124
impairments secondary to Morvan’s Syndrome was able to make significant functional gains after
125
working with physical, occupational, and speech therapies in an academic hospital inpatient
126
rehabilitation unit.
M AN U
SC
RI PT
115
TE D
127
In particular, a focus on neuromuscular rehabilitation, balance training, fine motor skills with
129
frequent verbal cueing in the context of strong family support allowed the patient to optimize
130
function with mobility and ADLs. Furthermore, the patient’s premorbid high executive functioning
131
cognitive status also may have increased his chances of improved cognitive recovery with
132
rehabilitation. While some of the patient’s FIM scores were unchanged or did not show significant
133
improvement from admission to discharge from acute inpatient rehabilitation, it is important to
134
note that the patient was discharged prematurely for seizures requiring acute care management
135
that could not be managed on the rehabilitation unit. This change in medical status most likely
136
impacted his FIM scores on day of discharge from the rehabilitation unit. Once medically
137
stabilized, he continued to demonstrate improvement in his FIM scores in acute care using the
AC C
EP
128
7
ACCEPTED MANUSCRIPT
same techniques used in inpatient rehabilitation. Overall, the intensive rehabilitation he received
139
improved his level of independence and decreased the burden of care required by his caregivers,
140
as subjectively reported by the patient’s wife, on discharge home.
RI PT
138
141
Information on how patients with Morvan’s Syndrome who receive definitive treatment for their
143
underlying condition perform in rehabilitation has not been commented upon in the medical
144
literature. This case report was limited to evaluation of rehabilitation in the acute care and
145
inpatient rehabilitation settings of an academic hospital. Further studies could evaluate the effects
146
of different rehabilitation settings (e.g. skilled nursing facilities, outpatient therapies, etc) on
147
functional progress in a patient with Morvan’s Syndrome.
M AN U
SC
142
148 149
153 154 155 156 157 158
EP
152
AC C
151
TE D
150
159 160
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ACCEPTED MANUSCRIPT
References
162
1. Liguori R, Vincent A, Clover L, et al. Morvan’s syndrome: peripheral and central nervous system
163
and cardiac involvement with antibodies to voltage-gated potassium channels. Brain 2001; 124(Pt
164
12):2417-2426.
165
2. Misawa T, Mizusawa H. Anti-VGKC antibody-associated limbic encephalitis/Morvan syndrome.
166
Brain Nerve 2010; 62(4):339-345.
167
3. Lee EK, Maselli RA, Ellis WG, Agius MA. Morvan’s fibrillary chorea: a paraneoplastic
168
manifestation of thymoma. J Neurol Neurosurg Psychiatry 1998; 65:857-862.
169
4. Galié E, Renna R, Plantone D, et al Paraneoplastic Morvan’s syndrome following surgical
170
treatment of recurrent thymoma: A case report. Oncol Lett 2016; 12(4):2716-2719
171
5. Nasreddine, Z. Montreal Cognitive Assessment: MOCA Test Full 7.1 English. Electronic test,
172
August 2010. Available at External link http://www.mocatest.org/electronic-tests/. Accessed
173
August 20, 2017.
174
6. Uniform Data System for Medical Rehabilitation. The FIM Instrument: Its Background, Structure,
175
and Usefulness. Adobe Portable Document Format, 2012. Available at External link
176
https://www.udsmr.org/Documents/The_FIM_Instrument_Background_Structure_and_Usefulnes
177
s.pdf. Accessed August 20, 2017.
179 180 181
SC
M AN U
TE D
EP
AC C
178
RI PT
161
182 183
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ACCEPTED MANUSCRIPT
Result
Lab
Result
Anti-VGKC Ab
Positive
HIV
Negative
Anti-CASPR2 Ab
Positive
HSV
Negative
Anti-LGI1 Ab
Positive
RPR
Negative
NMDA-R-Ab
Negative
VZV PCR
Negative
Thiamine
62 (Low)
ANNA 1, 2, 3
Negative
Vitamin B12
554 (Normal)
PCA 1, 2, 3
Negative
TSH
2.06 (Normal)
Thyroglobulin
Negative
Heavy Metals
Negative
Thyroid Peroxidase
Negative
SC
Lab
RI PT
Tables
M AN U
184
Table 1: Selected lab results included in the work-up of this patient leading to diagnosis of
186
Morvan’s Syndrome.
187
TE D
185
Ab = antibody; NMDA-R-Ab = N-methyl-D-aspartate receptor antibody; TSH = thyroid-stimulating
189
hormone; HIV = human immunodeficiency virus; HSV = herpes simplex virus; RPR = rapid plasma
190
reagin; VZV PCR = varicella-zoster virus polymerase chain reaction; ANNA 1, 2, 3 = anti-neuronal
191
nuclear antibodies 1, 2, 3; PCA 1, 2, 3 = purkinje cell cytoplasmic antibodies 1, 2, 3.
193 194
AC C
192
EP
188
195 196 197
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ACCEPTED MANUSCRIPT
M AN U
198
SC
RI PT
MOCA Test Scores (Points Scored/Total Possible Points) Admission to Discharge from Acute Acute Inpatient Care to Home Rehabilitation (HD 52) (HD 39) Visuospatial/Executive 2/5 5/5 Naming 2/3 2/3 Attention 1/6 6/6 Language 1/3 3/3 Abstraction 2/2 1/2 Delayed Recall 5/5 5/5 Orientation 4/6 6/6 TOTAL 17/30 28/30 Table 2: MOCA scores during different time points in patient’s hospital course.
199 200 201
205 206 207 208 209 210
EP
204
AC C
203
TE D
202
211 212 213
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ACCEPTED MANUSCRIPT
FIM Scores Admission to Acute Inpatient Rehabilitation (HD 38)
Discharge from Acute Inpatient Rehabilitation (HD 45)
Discharge from Acute Care (HD 54)
RI PT
Initial PM&R Consult While in Acute Care (HD 35) 1 5 5 4 2 5 2 2 2 2
215
UE = upper extremity; LE = lower extremity; WC=wheelchair.
AC C
EP
TE D
M AN U
SC
214
Bladder 1 6 6 Bowel 6 6 6 Eating 5 7 7 Grooming 2 5 5 Bathing 4 4 5 UE Dressing 5 5 6 LE Dressing 4 5 6 Toileting 2 5 5 Toilet Transfer 2 4 5 Tub/Shower 4 4 5 Transfer Bed/Chair/WC 2 2 2 6 Transfer Walk/WC mobility 4 (walk) 1/5 1/5 5/5 Stairs 1 1 3 3 Comprehension 2 3 6 6 Expression 2 3 5 7 Social Interaction 2 5 5 6 Problem Solving 1 2 2 5 Memory 1 2 2 5 Table 3: FIM instrument scores during various time points in patient’s hospital course.
12